James D Shelton a
The Lancet 2007; 370:1809-1811. DOI:10.1016/S0140-6736(07)61755-3
Despite substantial progress against AIDS worldwide, we are still
losing ground. The number of new infections continues to dwarf the
numbers who start antiretroviral therapy in developing countries.1,2
Most infections occur in widespread or generalised epidemics in
heterosexuals in just a few countries in southern and eastern Africa.
Although HIV incidence has fallen in Uganda, Kenya, and Zimbabwe, the
generalised epidemic rages on. Something is not working. Ten
misconceptions impede prevention.
HIV spreads like wildfire—Typically it does not. HIV is very
infectious in the first weeks when virus levels are high,3 but not in
the subsequent many-year quiescent phase. Only about 8% of people
whose primary heterosexual partners have the virus become infected
each year.4 Thus Kenya has more couples in which only one person is
infected than couples in which both are (figure).5 This low
infectiousness in heterosexual relationships partly explains why HIV
has spared most of the world's populations. However, the exceptional
generalised epidemics in Africa seem largely driven by concurrent
partnerships, in which some people have more than one regular
partner. This pattern allows rapid dissemination when a new infection
is introduced6 and probably involves more frequent risky sex than in
sporadic or exclusive relationships.
Sex work is the problem—Formal sex work is uncommon in these
generalised epidemics. In Lesotho, fewer than 2% of men reported
paying for sex in the previous year, although 29% reported multiple
partners.7 Nuanced economic support is an important enabler of
regular concurrent partnerships and transactional sex, but the
targeting of sex work in prevention campaigns has limited usefulness.
Men are the problem—The behaviour of men, including cross-
generational and coercive sex, contributes substantially to the
establishment of generalised epidemics. But a heterosexual epidemic
requires some women to have multiple partners.3 The importance of
women in generalised epidemics is evidenced by the high proportion
(sometimes the majority) of discordant couples in which the woman,
not the man, is HIV positive (figure).5
Adolescents are the problem—Generalised epidemics span all
reproductive ages. Although adolescent women are affected through sex
with older men, HIV incidence increases in women in their 20s and
later in life.8 Men are infected at even older ages. Thus
interventions in young people, including abstinence, although
important, have limited usefulness.
Poverty and discrimination are the problem—These factors can surely
engender risky sex. But HIV is paradoxically more common in wealthier
people than in poorer people, perhaps because wealth and mobility
support concurrent sexual partnerships.9 Moreover, HIV has declined
without major improvements in poverty and discrimination, notably in
Zimbabwe (notwithstanding substantial economic and social distress).
Condoms are the answer—Condom use, especially by sex workers, is
crucial to the containment of concentrated epidemics, and condoms
help to protect some individuals. But condoms alone have limited
impact in generalised epidemics. Many people dislike using them
(especially in regular relationships), protection is imperfect, use
is often irregular, and condoms seem to foster disinhibition, in
which people engage in risky sex either with condoms or with the
intention of using condoms.8
HIV testing is the answer—That learning one's HIV status (hopefully
with counselling) should lead to behavioural change and reduced risk
seems intuitive. However, real-world evidence of such change is
discouraging, especially for the large majority who test negative.3
Moreover any changes must be sustained for years. And very newly
infected people, who are highly infectious, do not yet test HIV-
positive.
Treatment is the answer—Theoretically, treatment and counselling
might aid prevention by lowering viral levels (and infectiousness) in
those treated, reducing denial about HIV, and promoting behavioural
change. However, no clear effect has emerged. Indeed these salutary
effects might be outweighed by negative effects, such as resumption
of sexual activity once those on antiretrovirals feel well, and
disinhibition when people realise that HIV might no longer be a death
sentence.
New technology is the answer—Many resources are devoted to vaccines,
microbicides, and prophylactic antiretrovirals. Unfortunately any
success appears to be far off. Moreover, such innovations might be
mainly targeted only at very high-risk populations, rely on
behavioural compliance, and engender disinhibition.10 Similarly,
treatment of sexually transmitted infections to prevent HIV has been
disappointing.11 Even male circumcision, an already available,
unmistakably effective, and compelling priority will take years to
have additional substantial effect.
Sexual behaviour will not change—Actually, facing the prospect of
deadly illness, many people will change. Homosexual men in the USA
radically changed behaviour in the 1980s. And the reductions in HIV
incidence in Kenya and eastern Zimbabwe were accompanied by large
drops in multiple partners,8,12 probably largely as a spontaneous
reaction to fear.
Truthfully, our priority must be on the key driver of generalised
epidemics—concurrent partnerships. Although many people sense that
multiple partners are risky, they do not realise the particular risk
of concurrent partnerships. Indeed, technical appreciation of their
role is recent.6 But partner limitation has also been neglected
because of the culture wars between advocates of condoms and
advocates of abstinence, because it smacks of moralising, because
mass behavioural change is alien to most medical professionals, and
because of the competing priorities of HIV programmes.
Fortunately we can enhance partner-limitation behaviour, akin to the
behaviour change that many people have adopted spontaneously. State-
of-the-art behaviour-change techniques, including explicit messages,
that are sensitive to local cultures, can raise perception of
personalised risk. Even modest reductions in concurrent partnerships
could substantially dampen the epidemic dynamic. Other prevention
approaches also have merit, but they can be much more effective in
conjunction with partner-limitation. Now, more than 20 years into HIV
prevention, we have to get it right.
I thank Daniel Halperin and Willard Cates for helpful ideas on this
Comment. My views here are not necessarily those of USAID. I declare
that I have no conflict of interest.
References
1. UNAIDS, WHO. AIDS epidemic update. December, 2007:
http://data.unaids.org/pub/EPISlides/2007/2007_epiupdat...
(accessed Nov 21, 2007)..
2. World Health Organization, UNAIDS, UNICEF. Towards universal
access: scaling up priority HIV/AIDS interventions in the health
sector. Progress report, April 2007. April 17, 2007:
http://www.who.int/hiv/mediacentre/univeral_access_prog...
(accessed Nov 21, 2007)..
3. Cassell MM, Surdo A. Testing the limits of case finding for HIV
prevention. Lancet Infect Dis 2007; 7: 491-495.
4. Wawer MJ, Gray RH, Sewankambo NK, et al. Rates of HIV-1
transmission per coital act by stage of HIV-1 infection, in Rakai,
Uganda. J Infect Dis 2005; 191: 1403-1409.
5. Central Bureau of Statistics, Ministry of Health Kenya, Kenya
Medical Research Institute, Centers for Disease Control and
Prevention Kenya, ORC Macro. Kenya demographic and health survey
2003. 2004:
http://www.measuredhs.com/pubs/pub_details.cfm?ID=462&c...
(accessed Nov 21, 2007)..
6. Halperin D, Epstein H. Concurrent sexual partnerships help to
explain Africa's high level of HIV prevalence: implications for
Pevention. Lancet 2004; 364: 4-6.
7. Ministry of Health and Social Welfare Lesotho, Bureau of
Statistics Lesotho, ORC Macro. Lesotho demographic and health survey
2004. 2005:
http://www.measuredhs.com/aboutsurveys/search/metadata....
(accessed Nov 21, 2007).
8. Shelton JD. Confessions of a condom lover. Lancet 2006; 368: 1947-
1949.
9. Shelton JD, Cassell MM, Adetunji J. Is poverty or wealth at the
root of HIV?. Lancet 2005; 366: 1057-1058.
10. Imrie J, Elford J, Kippax S, Hart G. Biomedical HIV prevention—
and social science. Lancet 2007; 370: 10-11.
11. Gray RH, Wawer MJ. Randomized trials of HIV prevention. Lancet
2007; 370: 200-201.
12. Gregson S, Garnett GP, Nyamukapa CA, et al. HIV decline
associated with behavior change in eastern Zimbabwe. Science 2006;
311: 664-666.
Affiliations
a. Bureau for Global Health, US Agency for International Development,
Washington, DC 20523, USA
Saturday 29 December 2007
Saturday 8 December 2007
Post-exposure HIV drugs won't boost risky behavior
Fri Nov 23, 2007 12:11pm EST
By Anne Harding
NEW YORK (Reuters Health) - Giving antiretroviral drugs to people after they may have been exposed to HIV is an effective way to prevent them from contracting the virus, a new study shows.
What's more, people who know this option is available to them don't appear to be more likely to engage in risky behavior, Dr. Steve Shoptaw of the UCLA Department of Family Medicine in Los Angeles, who was involved in the research, told Reuters Health. "This is a viable way of helping people stay (HIV)-negative, " he said.
So-called post-exposure prophylaxis, or PEP, has long been available to people who risk HIV infection on the job, for example a health care worker accidentally jabbed by a contaminated syringe. In 2005, the Centers for Disease Control and Prevention expanded its PEP guidelines to cover people exposed to HIV outside the workplace, for example through risky sex, condom breakage or drug use. But PEP still isn't widely used in such cases, Shoptaw and his team note, because it isn't covered by health insurance and is only very rarely offered as part of community health programs.
To investigate the feasibility of a community organized and funded non-occupational PEP program, the researchers conducted a demonstration project in which people were offered a 28-day course of anti-HIV drugs within 72 hours of potential exposure to HIV.
One hundred people, 95 of them men, participated. They received the drug treatment, HIV testing, and counseling for up to 26 weeks after enrolling in the study. Fifty-eight participants reported having unprotected anal sex, while 18 percent reported condom breakage.
Among the 84 people given the full course of medication, 75 percent actually took all the drugs. No one became HIV-positive during the course of the study.
Some health authorities have been reluctant to offer PEP after risky sex or drug use for fear that people wouldn't change their behavior if they knew "there's a parachute somewhere they can take to stay negative," Shoptaw noted. However, he and his colleagues found people reduced their risk behavior after using PEP, rather than increasing it.
He and his colleagues call for making non-occupational PEP programs more widely available to people at high risk of becoming infected with HIV. For now, Shoptaw noted, PEP is available only to people who can access it and pay for it out of pocket -- drugs and counseling together cost about $2,200.
Right now, "this is more of a social justice issue," Shoptaw said. "People who have means have access to this, people who don't, don't."
SOURCE: AIDS Care, published online October 24, 2007.
© Reuters 2006. All rights reserved.
By Anne Harding
NEW YORK (Reuters Health) - Giving antiretroviral drugs to people after they may have been exposed to HIV is an effective way to prevent them from contracting the virus, a new study shows.
What's more, people who know this option is available to them don't appear to be more likely to engage in risky behavior, Dr. Steve Shoptaw of the UCLA Department of Family Medicine in Los Angeles, who was involved in the research, told Reuters Health. "This is a viable way of helping people stay (HIV)-negative, " he said.
So-called post-exposure prophylaxis, or PEP, has long been available to people who risk HIV infection on the job, for example a health care worker accidentally jabbed by a contaminated syringe. In 2005, the Centers for Disease Control and Prevention expanded its PEP guidelines to cover people exposed to HIV outside the workplace, for example through risky sex, condom breakage or drug use. But PEP still isn't widely used in such cases, Shoptaw and his team note, because it isn't covered by health insurance and is only very rarely offered as part of community health programs.
To investigate the feasibility of a community organized and funded non-occupational PEP program, the researchers conducted a demonstration project in which people were offered a 28-day course of anti-HIV drugs within 72 hours of potential exposure to HIV.
One hundred people, 95 of them men, participated. They received the drug treatment, HIV testing, and counseling for up to 26 weeks after enrolling in the study. Fifty-eight participants reported having unprotected anal sex, while 18 percent reported condom breakage.
Among the 84 people given the full course of medication, 75 percent actually took all the drugs. No one became HIV-positive during the course of the study.
Some health authorities have been reluctant to offer PEP after risky sex or drug use for fear that people wouldn't change their behavior if they knew "there's a parachute somewhere they can take to stay negative," Shoptaw noted. However, he and his colleagues found people reduced their risk behavior after using PEP, rather than increasing it.
He and his colleagues call for making non-occupational PEP programs more widely available to people at high risk of becoming infected with HIV. For now, Shoptaw noted, PEP is available only to people who can access it and pay for it out of pocket -- drugs and counseling together cost about $2,200.
Right now, "this is more of a social justice issue," Shoptaw said. "People who have means have access to this, people who don't, don't."
SOURCE: AIDS Care, published online October 24, 2007.
© Reuters 2006. All rights reserved.
Deputy governor unwavering on plan to legalize prostitution
Friday, November 23, 2007
Prodita Sabarini, The Jakarta Post, Denpasar
Bali Deputy Governor Alit Kesuma Kelakan has said he will push ahead
with plans to recognize and provide support to prostitutes in an attempt
to halt the spread of HIV/AIDS on the island, despite objections from
Governor Dewa Made Beratha.
Kelakan's plan involves declaring known prostitution zones safe from
persecution in order to encourage the women to access health services.
"Approved or not, I will go ahead with the program," Kelakan said.
Kelakan, who is chairman of the Bali chapter of the National AIDS
Commission (KPAD Bali), said he believed such policy a would enable
health-related agencies to better identify and reach HIV/AIDS high-risk
groups to curb the spread of the virus through sexual contact.
KPAD Bali data show that more than half of the island's HIV/AIDS
patients were infected with the virus through sexual contact.
According to the Kerti Praja Foundation, an organization working on
HIV/AIDS prevention in the island, Bali has around 8,800 sex workers
with a customer base of around 85,000.
Research by the foundation in 2006 also found that 14 percent of sex
workers in Bali are infected with the virus.
In a plenary meeting with the Bali Regional Legislative Council earlier
this month, Beratha firmly rejected Kelakan's proposal. He said that the
policy of acknowledging and accepting the prostitution areas would
suggest that the practice of prostitution has been legalized.
He said this was clearly in opposition to Bali's religious teachings,
customs and culture.
The Indonesian Criminal Code states that prostitution is illegal.
However, commercial sex workers are common in tourist areas of Bali such
as Sanur and Kuta.
Kelakan has said that law enforcement has been ineffective in stopping
the practice, which stems from more complex issues of poverty, poor
education and unemployment.
He policy suggestion has also met with resistance from legislators and
the Indonesian Hindu Council. The Council of Customary Villages
initially objected to the plan but later accepted it.
Kelakan said that KPAD Bali will carry out strict supervision programs
at known prostitution areas in a number of regencies, including the
regular monitoring of sex workers' health.
"KPAD and other non-governmental organizations have already carried out
campaign programs for sex workers, so without the government
implementing the program in its budget, KPAD's and the NGOs' programs
would still go on. However, it would only be partial (in its coverage
and impact). It would not be a systemized program and would certainly
not be a sustainable one. What we need is a sustainable program
supported by the government," he said.
Kelakan said that positive developments had been seen in Badung regency,
where the government and local council there were deliberating a bill on
HIV/AIDS prevention that would make it mandatory for owners of
entertainment places to educate their employees on HIV/AIDS and to
routinely check their employees' health status in relation to sexually
transmitted disease.
KPAD has estimated that the number of people living with HIV/AIDS on the
island exceed 4,000 as of August this year.
Head of Kerti Praja Nyoman Wirawan gave the "very conservative"
estimation that 840 men in Bali will contract the virus this year
through sexual contact with HIV-positive sex workers, with the
assumption that there are only 3,000 sex workers in Bali, with one
customer per day, working 250 days per year.
The estimate doesn't account for other potential infected people, such
as the sexual partners of customers and the babies of pregnant
HIV-positive- mothers.
"Imagine Bali in 10 to 20 years. If we don't do anything there will be a
lost generation of Balinese due to HIV/AIDS. The government is nothing
but a hypocrite if it does not try to do anything about this," he said.
Prodita Sabarini, The Jakarta Post, Denpasar
Bali Deputy Governor Alit Kesuma Kelakan has said he will push ahead
with plans to recognize and provide support to prostitutes in an attempt
to halt the spread of HIV/AIDS on the island, despite objections from
Governor Dewa Made Beratha.
Kelakan's plan involves declaring known prostitution zones safe from
persecution in order to encourage the women to access health services.
"Approved or not, I will go ahead with the program," Kelakan said.
Kelakan, who is chairman of the Bali chapter of the National AIDS
Commission (KPAD Bali), said he believed such policy a would enable
health-related agencies to better identify and reach HIV/AIDS high-risk
groups to curb the spread of the virus through sexual contact.
KPAD Bali data show that more than half of the island's HIV/AIDS
patients were infected with the virus through sexual contact.
According to the Kerti Praja Foundation, an organization working on
HIV/AIDS prevention in the island, Bali has around 8,800 sex workers
with a customer base of around 85,000.
Research by the foundation in 2006 also found that 14 percent of sex
workers in Bali are infected with the virus.
In a plenary meeting with the Bali Regional Legislative Council earlier
this month, Beratha firmly rejected Kelakan's proposal. He said that the
policy of acknowledging and accepting the prostitution areas would
suggest that the practice of prostitution has been legalized.
He said this was clearly in opposition to Bali's religious teachings,
customs and culture.
The Indonesian Criminal Code states that prostitution is illegal.
However, commercial sex workers are common in tourist areas of Bali such
as Sanur and Kuta.
Kelakan has said that law enforcement has been ineffective in stopping
the practice, which stems from more complex issues of poverty, poor
education and unemployment.
He policy suggestion has also met with resistance from legislators and
the Indonesian Hindu Council. The Council of Customary Villages
initially objected to the plan but later accepted it.
Kelakan said that KPAD Bali will carry out strict supervision programs
at known prostitution areas in a number of regencies, including the
regular monitoring of sex workers' health.
"KPAD and other non-governmental organizations have already carried out
campaign programs for sex workers, so without the government
implementing the program in its budget, KPAD's and the NGOs' programs
would still go on. However, it would only be partial (in its coverage
and impact). It would not be a systemized program and would certainly
not be a sustainable one. What we need is a sustainable program
supported by the government," he said.
Kelakan said that positive developments had been seen in Badung regency,
where the government and local council there were deliberating a bill on
HIV/AIDS prevention that would make it mandatory for owners of
entertainment places to educate their employees on HIV/AIDS and to
routinely check their employees' health status in relation to sexually
transmitted disease.
KPAD has estimated that the number of people living with HIV/AIDS on the
island exceed 4,000 as of August this year.
Head of Kerti Praja Nyoman Wirawan gave the "very conservative"
estimation that 840 men in Bali will contract the virus this year
through sexual contact with HIV-positive sex workers, with the
assumption that there are only 3,000 sex workers in Bali, with one
customer per day, working 250 days per year.
The estimate doesn't account for other potential infected people, such
as the sexual partners of customers and the babies of pregnant
HIV-positive- mothers.
"Imagine Bali in 10 to 20 years. If we don't do anything there will be a
lost generation of Balinese due to HIV/AIDS. The government is nothing
but a hypocrite if it does not try to do anything about this," he said.
Stephen Lewis damns UNAIDS over statistics revision; diverts from the
Rob Dawson, Thursday, November 29, 2007
In a passionate speech at the World Health Editors Network in London,
a former United Nations Special Envoy for AIDS in Africa and
Co-Director of AIDS-Free World, Stephen Lewis, warned that a recent
UNAIDS document reporting decreased HIV infections has "undermined
public confidence in the reliability of the figures, introducing
completely unnecessary levels of doubt, contention and confusion".
Describing the UN as "stubborn and sloppy", he expressed concern that
the report does nothing to convince the world that we are "billions
and billions of dollars behind, when it comes to funding all the
components of the pandemic, from orphans to second line drugs."
In its latest report, UNAIDS cut the number of infections worldwide to
about 32.7 million, down from its estimated 39.5 million in 2006.
Rather than a reduction based on decreased rates of infection, the new
figure was mainly due to fixing flawed statistics from previous reports.
The former data collection methods relied heavily on "sentinel-site
surveillance" which extrapolates data gathered at prenatal clinics.
An assumption was made that the rate of HIV in the general population
would be similar to the rate among pregnant women in urban clinics.
This year the UN attributed more of their calculations to national surveys
and blood-testing.
While it's good news that fewer people are infected than previously
thought, there was concern that the dramatic re-representation of the
figures would result in diverted resources from an epidemic still in
desperate need of funds.
"For years, knowledgeable epidemiologists have been telling the UN
that the figures were too high. They didn't whisper their criticisms:
they wrote books and articles," Lewis said. "But the UN chose a course
of delay and dithering. It can never admit that it's wrong. So finally,
and predictably, came the moment of truth: the result is an overall
prevalence rate that is lower by almost seven million than last year's
estimate."
Lewis also expressed anger that the report did not address the human
tragedy and focused too much on statistics.
"The new estimates confirm a continuing apocalypse for sub-Saharan
Africa: 22.5 million infections, 61% of them women, 68% of world-wide
infections, 76% of all deaths, 11.4 million orphans. This is where the
focus must be, this is where it should always have been; not a report
cluttered by mathematical adjustments so that virtually every story
that's written begins with the news of a statistical volte-face. If the
recording of data had been more scrupulous all along, we could have
welcomed this report," he said. "Instead, all of us have to run to the
trenches to remind the world that more money is still desperately needed."
Lewis also highlighted several flaws in the data which could lead to
yet another recalculation. For example, the narrative evidence of the
report states repeatedly that Mozambique has shown no decrease in
infection rates yet later asserts that Mozambique is one of the six
countries in the world that has most significantly contributed to the
reduced numbers seen in the report. No data on Mozambique is set out
conclusively in the report.
In conclusion, Lewis stressed that more should be done no matter what
statistical calculation is applied to the figures.
"Whether it's 40 million or 33 million, this plague continues to
ravage humankind. I simply do not believe that the United Nations has
done everything it can possibly do to turn the tide," he said.
In a passionate speech at the World Health Editors Network in London,
a former United Nations Special Envoy for AIDS in Africa and
Co-Director of AIDS-Free World, Stephen Lewis, warned that a recent
UNAIDS document reporting decreased HIV infections has "undermined
public confidence in the reliability of the figures, introducing
completely unnecessary levels of doubt, contention and confusion".
Describing the UN as "stubborn and sloppy", he expressed concern that
the report does nothing to convince the world that we are "billions
and billions of dollars behind, when it comes to funding all the
components of the pandemic, from orphans to second line drugs."
In its latest report, UNAIDS cut the number of infections worldwide to
about 32.7 million, down from its estimated 39.5 million in 2006.
Rather than a reduction based on decreased rates of infection, the new
figure was mainly due to fixing flawed statistics from previous reports.
The former data collection methods relied heavily on "sentinel-site
surveillance" which extrapolates data gathered at prenatal clinics.
An assumption was made that the rate of HIV in the general population
would be similar to the rate among pregnant women in urban clinics.
This year the UN attributed more of their calculations to national surveys
and blood-testing.
While it's good news that fewer people are infected than previously
thought, there was concern that the dramatic re-representation of the
figures would result in diverted resources from an epidemic still in
desperate need of funds.
"For years, knowledgeable epidemiologists have been telling the UN
that the figures were too high. They didn't whisper their criticisms:
they wrote books and articles," Lewis said. "But the UN chose a course
of delay and dithering. It can never admit that it's wrong. So finally,
and predictably, came the moment of truth: the result is an overall
prevalence rate that is lower by almost seven million than last year's
estimate."
Lewis also expressed anger that the report did not address the human
tragedy and focused too much on statistics.
"The new estimates confirm a continuing apocalypse for sub-Saharan
Africa: 22.5 million infections, 61% of them women, 68% of world-wide
infections, 76% of all deaths, 11.4 million orphans. This is where the
focus must be, this is where it should always have been; not a report
cluttered by mathematical adjustments so that virtually every story
that's written begins with the news of a statistical volte-face. If the
recording of data had been more scrupulous all along, we could have
welcomed this report," he said. "Instead, all of us have to run to the
trenches to remind the world that more money is still desperately needed."
Lewis also highlighted several flaws in the data which could lead to
yet another recalculation. For example, the narrative evidence of the
report states repeatedly that Mozambique has shown no decrease in
infection rates yet later asserts that Mozambique is one of the six
countries in the world that has most significantly contributed to the
reduced numbers seen in the report. No data on Mozambique is set out
conclusively in the report.
In conclusion, Lewis stressed that more should be done no matter what
statistical calculation is applied to the figures.
"Whether it's 40 million or 33 million, this plague continues to
ravage humankind. I simply do not believe that the United Nations has
done everything it can possibly do to turn the tide," he said.
Sunday 25 November 2007
AIDS denial in Asia: Dimensions and roots
Health Policy, Volume 84, Issues 2-3, December 2007, Pages 133-141
Binod Nepal ,(nepalbinod@....
National Centre for Social and Economic Modelling, University of
Canberra, ACT 2601, Australia
Abstract
AIDS denial has long been viewed as the obstacle to forging effective
response in many Asian countries. This article examines the
dimensions and roots of this phenomenon. It identifies seven types of
views, attitudes, or tendencies that can be described as denial,
dissent, disagreements, or doubts.
Three major factors underlying the AIDS denial are discussed. These are (1)
historical impressions that STDs are Western diseases, (2) desire of some Asian
leaders to forge Eastern points of view, and (3) long-held negative image
towards the peoples or groups who happened to be at the front-line of the
population groups exposed to the epidemic. The third factor is the most
important source of denial.
AIDS denial is not a new and isolated phenomenon but the one shaped by the
global and historical institutions. Asian AIDS denial reflects the authoritarian
and moralist grievances arising from the perceived deterioration of traditional
moral order.
Fax: +61 2 6201 2751.
Health Policy. Volume 84, Issues 2-3, December 2007, Pages 133-141
doi:10.1016/j.healthpol.2007.04.011
Copyright © 2007 Elsevier Ireland Ltd All rights reserved.
Binod Nepal ,(nepalbinod@....
National Centre for Social and Economic Modelling, University of
Canberra, ACT 2601, Australia
Abstract
AIDS denial has long been viewed as the obstacle to forging effective
response in many Asian countries. This article examines the
dimensions and roots of this phenomenon. It identifies seven types of
views, attitudes, or tendencies that can be described as denial,
dissent, disagreements, or doubts.
Three major factors underlying the AIDS denial are discussed. These are (1)
historical impressions that STDs are Western diseases, (2) desire of some Asian
leaders to forge Eastern points of view, and (3) long-held negative image
towards the peoples or groups who happened to be at the front-line of the
population groups exposed to the epidemic. The third factor is the most
important source of denial.
AIDS denial is not a new and isolated phenomenon but the one shaped by the
global and historical institutions. Asian AIDS denial reflects the authoritarian
and moralist grievances arising from the perceived deterioration of traditional
moral order.
Fax: +61 2 6201 2751.
Health Policy. Volume 84, Issues 2-3, December 2007, Pages 133-141
doi:10.1016/j.healthpol.2007.04.011
Copyright © 2007 Elsevier Ireland Ltd All rights reserved.
Thursday 22 November 2007
UN slashes AIDS estimates to 33 million
http://au.news.yahoo.com/071120/2/150ly.html#
Tuesday November 20, 03:12 PM
The United Nations has slashed its estimates of how many people are infected with the AIDS virus, from nearly 40 million to 33 million.
In a report, the UN says revised estimates on HIV in India account for a large part of the decrease.
The agency admitted it overestimated how many people were infected with the incurable virus, and said better methods of collecting data showed it was not quite a common as feared.
"The single biggest reason for this reduction was the intensive exercise to assess India's HIV epidemic, which resulted in a major revision of that country's estimates," the report said.
After originally estimating some 5.7 million people were infected in India, the UN more than halved that estimate, to 2.5 million.
But the numbers nonetheless show the epidemic is overwhelming and that efforts to fight HIV must still be stepped up, said officials at the UN AIDS agency UNAIDS.
"These improved data present us with a clearer picture of the AIDS epidemic, one that reveals both challenges and opportunities," UNAIDS Executive Director Dr Peter Piot said in a statement.
"Unquestionably, we are beginning to see a return on investment - new HIV infections and mortality are declining and the prevalence of HIV levelling. But with more than 6,800 new infections and over 5,700 deaths each day due to AIDS, we must expand our efforts in order to significantly reduce the impact of AIDS worldwide."
The new numbers suggest that some 33.2 million people are infected with the human immunodeficiency virus - about 30.8 million adults and 2.5 million children.
UNAIDS estimated that 1.7 million people became newly infected in sub-Saharan Africa this year, a significant reduction since 2001.
But Africa remains by far the continent hardest hit by AIDS, with 22.5 million people infected with HIV.
"Eight countries in this region now account for almost one-third of all new HIV infections and AIDS deaths globally," said UNAIDS.
"In Asia, the estimated number of people living with HIV in Vietnam has more than doubled between 2000 and 2005 and Indonesia has the fastest growing epidemic."
The report gives two reasons for the downward revisions - one is better data and the other is an actual decrease in the number of new infections.
"UNAIDS and (the World Health Organisation) are now working with better information from many more countries," UNAIDS said.
The number of new HIV infections each year likely peaked in the late 1990s at 3 million and was estimated at 2.5 million for 2007, UNAIDS said.
"This reflects natural trends in the epidemic, as well as the result of HIV prevention efforts. Of the total difference in the estimates published in 2006 and 2007, 70 per cent are due to changes in six countries: Angola, India, Kenya, Mozambique, Nigeria, and Zimbabwe," the report said.
"In both Kenya and Zimbabwe, there is increasing evidence that a proportion of the declines is due to a reduction of the number of new infections which is, in part due to a reduction in risky behaviours."
The UN also changed its estimate on how long it takes to die of AIDS if not treated from 9 years to 11 years.
Tuesday November 20, 03:12 PM
The United Nations has slashed its estimates of how many people are infected with the AIDS virus, from nearly 40 million to 33 million.
In a report, the UN says revised estimates on HIV in India account for a large part of the decrease.
The agency admitted it overestimated how many people were infected with the incurable virus, and said better methods of collecting data showed it was not quite a common as feared.
"The single biggest reason for this reduction was the intensive exercise to assess India's HIV epidemic, which resulted in a major revision of that country's estimates," the report said.
After originally estimating some 5.7 million people were infected in India, the UN more than halved that estimate, to 2.5 million.
But the numbers nonetheless show the epidemic is overwhelming and that efforts to fight HIV must still be stepped up, said officials at the UN AIDS agency UNAIDS.
"These improved data present us with a clearer picture of the AIDS epidemic, one that reveals both challenges and opportunities," UNAIDS Executive Director Dr Peter Piot said in a statement.
"Unquestionably, we are beginning to see a return on investment - new HIV infections and mortality are declining and the prevalence of HIV levelling. But with more than 6,800 new infections and over 5,700 deaths each day due to AIDS, we must expand our efforts in order to significantly reduce the impact of AIDS worldwide."
The new numbers suggest that some 33.2 million people are infected with the human immunodeficiency virus - about 30.8 million adults and 2.5 million children.
UNAIDS estimated that 1.7 million people became newly infected in sub-Saharan Africa this year, a significant reduction since 2001.
But Africa remains by far the continent hardest hit by AIDS, with 22.5 million people infected with HIV.
"Eight countries in this region now account for almost one-third of all new HIV infections and AIDS deaths globally," said UNAIDS.
"In Asia, the estimated number of people living with HIV in Vietnam has more than doubled between 2000 and 2005 and Indonesia has the fastest growing epidemic."
The report gives two reasons for the downward revisions - one is better data and the other is an actual decrease in the number of new infections.
"UNAIDS and (the World Health Organisation) are now working with better information from many more countries," UNAIDS said.
The number of new HIV infections each year likely peaked in the late 1990s at 3 million and was estimated at 2.5 million for 2007, UNAIDS said.
"This reflects natural trends in the epidemic, as well as the result of HIV prevention efforts. Of the total difference in the estimates published in 2006 and 2007, 70 per cent are due to changes in six countries: Angola, India, Kenya, Mozambique, Nigeria, and Zimbabwe," the report said.
"In both Kenya and Zimbabwe, there is increasing evidence that a proportion of the declines is due to a reduction of the number of new infections which is, in part due to a reduction in risky behaviours."
The UN also changed its estimate on how long it takes to die of AIDS if not treated from 9 years to 11 years.
Tuesday 13 November 2007
Joint Statement of the Three Delegations in support of Civil Society's uniquerole in responding to HIV/TB/Malaria in ChinaKunming, China, 16 th Global
November 12, 2007
Having had some extremely valuable formal and informal interactions with a range of China Civil Society and Communities representatives over the last 5 days, the Communities Delegation along with Developed and Developing Country NGOs Delegation would like to strongly recommend to the Global Fund Board that a special attention is given to the need for strengthening Civil Society involvement and participation in the implementation of GF programs in China.
As with all grants there will be challenges in implementation. In particular, in the case of China and the recently-approved round 6, community and grassroots organizations cannot register to be legally recognized as civil society organizations.
We expect that these grassroots organizations, registered or not, should have access to the funds so that the implementation efforts will reflect the desired goal of the proposed program.
We, the members of the three civil society delegations to the Fund feel responsible and accountable to ensure that our counterparts in China are alsoable to access and utilize the opportunities of being a stakeholder in the Global Fund.
We are committed to ensure that the voices and aspirations of all communities living with the diseases in China are heard and that their basic rights, particularly the right to information and services are properly secured.
We expect the Global Fund to take the lead in ensuring its commitment to strengthen capacity building and mobilization of Civil Society across the world, including China, so that our collective goal of containing and reversing the spread of HIV/TB/Malaria is achieved.
We, the three civil society delegations, will continue to proactively engage with Chinese civil society to ensure their key role in the response tothe three diseases is recognized and we will work in close collaboration withall of you until this is achieved.
Communities Delegation
Developed Countries NGO Delegation
Developing Countries NGO Delegation to the Global Fund Board
Published at AIDS-ASIA yahoogroups, Tuesday, November 13,2007
Having had some extremely valuable formal and informal interactions with a range of China Civil Society and Communities representatives over the last 5 days, the Communities Delegation along with Developed and Developing Country NGOs Delegation would like to strongly recommend to the Global Fund Board that a special attention is given to the need for strengthening Civil Society involvement and participation in the implementation of GF programs in China.
As with all grants there will be challenges in implementation. In particular, in the case of China and the recently-approved round 6, community and grassroots organizations cannot register to be legally recognized as civil society organizations.
We expect that these grassroots organizations, registered or not, should have access to the funds so that the implementation efforts will reflect the desired goal of the proposed program.
We, the members of the three civil society delegations to the Fund feel responsible and accountable to ensure that our counterparts in China are alsoable to access and utilize the opportunities of being a stakeholder in the Global Fund.
We are committed to ensure that the voices and aspirations of all communities living with the diseases in China are heard and that their basic rights, particularly the right to information and services are properly secured.
We expect the Global Fund to take the lead in ensuring its commitment to strengthen capacity building and mobilization of Civil Society across the world, including China, so that our collective goal of containing and reversing the spread of HIV/TB/Malaria is achieved.
We, the three civil society delegations, will continue to proactively engage with Chinese civil society to ensure their key role in the response tothe three diseases is recognized and we will work in close collaboration withall of you until this is achieved.
Communities Delegation
Developed Countries NGO Delegation
Developing Countries NGO Delegation to the Global Fund Board
Published at AIDS-ASIA yahoogroups, Tuesday, November 13,2007
Interpol to fight sale of fake medicines in Africa
http://health.yahoo.com/news/afp/policeinterpolafricacounterfeitme
dicinehealth-print.html
By AFP
International police body Interpol will join the fight against the
growing trade in Africa in fake drugs for tuberculosis, malaria and
HIV/AIDS which threatens the lives of thousands, a senior official
said Tuesday.(AFP/File/Issouf Sanogo)
MARRAKECH, Morocco (AFP) - International police body Interpol
will join the fight against the growing trade in Africa in fake drugs for
tuberculosis, malaria and HIV/AIDS which threatens the lives of
thousands, a senior official said Tuesday.
The agency's efforts will begin later this year and will build on its
success in tackling the problem in Latin America and Southeast Asia,
said John Newton, the manager of Interpol's intellectual property
rights project.
"We have learned a lot of lessons in those regions and we are now
able to apply those to Africa," he told AFP on the sidelines of
Interpol's annual general assembly in Marrakech in southern Morocco.
Congo, Nigeria, Senegal and Sudan asked the 186-member police
body at the gathering for for help in stopping smuggling networks
from making fake drugs readily available in their markets and
sometimes even pharmacies, he said.
"The Africans are very keen for Interpol to work with them on this
subject," said Newton.
Interpol will train police in Africa on how to smash counterfeit
medicine smuggling networks, coordinate police operations and track
the flow of fake drugs from southeast Asia and other parts of the
world to the continent.
As it has in other regions, the global police body will work with the
World Health Organization and drug companies to tackle the problem.
"We can bridge the gap between law enforcement and the public
health sector, we are able to bring the two areas together," said Newton.
The World Health Organization estimates that up to 30 percent of the
medicine sold in Africa is fake.
Counterfeit medicine networks take advantage of Africa's poor or
non-existent drug regulatory systems to dump drugs with little or no
active ingredient in the continent, experts say.
Interpol carried out its first-ever operation solely dedicated to the
trade in fake medicine in 2005 in seven southeast Asian countries.
"We are concerned about counterfeit medicines for life-threatening
diseases such as malaria, tuberculosis and HIV/AIDS and increasingly
getting involved in this area," said Newton.
The US-based Center for Medicines in the Public Interest estimates
that global counterfeit drug sales will rise to 75 billion dollars by
2010, a 90 percent increase over 2005.
dicinehealth-print.html
By AFP
International police body Interpol will join the fight against the
growing trade in Africa in fake drugs for tuberculosis, malaria and
HIV/AIDS which threatens the lives of thousands, a senior official
said Tuesday.(AFP/File/Issouf Sanogo)
MARRAKECH, Morocco (AFP) - International police body Interpol
will join the fight against the growing trade in Africa in fake drugs for
tuberculosis, malaria and HIV/AIDS which threatens the lives of
thousands, a senior official said Tuesday.
The agency's efforts will begin later this year and will build on its
success in tackling the problem in Latin America and Southeast Asia,
said John Newton, the manager of Interpol's intellectual property
rights project.
"We have learned a lot of lessons in those regions and we are now
able to apply those to Africa," he told AFP on the sidelines of
Interpol's annual general assembly in Marrakech in southern Morocco.
Congo, Nigeria, Senegal and Sudan asked the 186-member police
body at the gathering for for help in stopping smuggling networks
from making fake drugs readily available in their markets and
sometimes even pharmacies, he said.
"The Africans are very keen for Interpol to work with them on this
subject," said Newton.
Interpol will train police in Africa on how to smash counterfeit
medicine smuggling networks, coordinate police operations and track
the flow of fake drugs from southeast Asia and other parts of the
world to the continent.
As it has in other regions, the global police body will work with the
World Health Organization and drug companies to tackle the problem.
"We can bridge the gap between law enforcement and the public
health sector, we are able to bring the two areas together," said Newton.
The World Health Organization estimates that up to 30 percent of the
medicine sold in Africa is fake.
Counterfeit medicine networks take advantage of Africa's poor or
non-existent drug regulatory systems to dump drugs with little or no
active ingredient in the continent, experts say.
Interpol carried out its first-ever operation solely dedicated to the
trade in fake medicine in 2005 in seven southeast Asian countries.
"We are concerned about counterfeit medicines for life-threatening
diseases such as malaria, tuberculosis and HIV/AIDS and increasingly
getting involved in this area," said Newton.
The US-based Center for Medicines in the Public Interest estimates
that global counterfeit drug sales will rise to 75 billion dollars by
2010, a 90 percent increase over 2005.
Saturday 10 November 2007
Russian scientists offer hope for HIV vaccine
http://en.rian.ru/russia/20071005/82647847.html
NOVOSIBIRSK October 5 (RIA Novosti) - Scientists at the Russian virology and biotechnology Vector research centre in Novosibirsk, West Siberia have developed a potential HIV vaccine.
"As we know there is no HIV vaccine. The Americans had high hopes of developing one, but the three vaccines developed most recently all failed trials. Today the specialists from Vector said there is a hope for an effective vaccine," a leading geneticist, Vladimir Shumny, said on Friday.
The scientist added that it is difficult to develop an HIV vaccine as the virus is constantly mutating. He also said that the polymorphous vaccine created by the research center might help to effectively prevent HIV, however.
At the same time, Shumny claimed that lengthy legal procedures could complicate the vaccine's chances of passing the necessary medical trials, not to mention getting it registered with the appropriate authorities.
"The first phase of trials will take at least three years," he explained.
A researcher at Vektor added that it was still too early to speak about the effectiveness of the vaccine, as the first phase of the trials has not started and its safety has not yet been proven.
A total of 37 HIV vaccines have been developed, but none of them have been successful, she added.
The Russian government has allocated one billion rubles ($39.4 million) to develop a HIV vaccine.
Since 1987, when the first HIV case was first reported in Russia, 388,871 cases have been registered in the country, and HIV-infected women have given birth to 1,200 children. Among the most infected areas in Russia are Moscow, Irkutsk, Samara, Orenburg, and the Leningrad Region.
At the end of 2005, 40.3 million people were HIV-infected worldwide, including 17.5 million women and 2.3 million children under the age of 15.
Pre-treatment CD4 Count Predicts CD4 Gains on Treatment
http://www.aidsmeds.com/articles/hiv_cd4_uk_1667_13356.shtml
October 30, 2007
By David EvansThe higher a person’s CD4 count upon starting HIV treatment, the higher their CD4 count will be 60 months later, say British researchers at the 11th European AIDS Conference in Madrid.
Rachael Hughes, MSc, of the department of social medicine at the University of Bristol in England, and her colleagues analyzed data involving 4,559 patients participating in the U.K. collaborative HIV Cohort (UK-CHIC), all of whom had maintained undetectable viral loads for at least six months after starting HIV treatment. Data were available for 631 patients who had been followed for greater than 60 months.
The research team found that CD4 gains were universally good among all of the patients in the study, regardless of their starting CD4 count. Those who started treatment with the lowest CD4 count, between 0 and 100, had the largest gains of up to 379 cells, while those who started with the highest, 500 and above, had the least gains, roughly 100 cells.
However, the average CD4 count 60 months after starting treatment was 100 cells lower among those who started treatment with CD4 counts between 350 and 499, compared with those who started with between 500 and 749 cells.
While these data suggest that people who start HIV treatment earlier will, on average, do better immunologically than those who start later, they also illustrate that almost all patients, regardless of their starting CD4 counts, can expect robust CD4 increases as a result of treatment. This research also concludes that CD4 gains are most noticeable during the first few months of treatment but do continue even after a year of treatment.
Source:
Hughes R, Sabin C, Sterne J. Long-term Trends in CD4 Count in Patients Starting HAART: UK-CHIC Study [Abstract P18.4/04] 11th European AIDS Conference, Madrid, 2007.Early Treatment Reduces Risk of Three Common Complications
http://www.aidsmeds.com/articles/kidney_neuropathy_anemia_1667_13376.shtml
November 2, 2007
Does starting HIV treatment early increase the risk of complications like peripheral neuropathy, anemia and kidney problems? On the contrary, say new data from the HIV Outpatient Study (HOPS) to be reported in an upcoming issue of the Journal of Acquired Immune Deficiency Syndromes (JAIDS).Peripheral neuropathy, anemia and kidney problems are common occurrences in people with HIV, notably those on antiretroviral (ARV) treatment. In turn, some experts have suggested that starting treatment earlier than is currently recommended—a CD4 count below 350 cells—may result in an upswing in these complications among otherwise healthy people living with the virus.
The HOPS investigators, under the direction of Kenneth Lichtenstein, MD, of the University of Colorado in Denver followed 2,165 HIV-positive patients who started ARV treatment with varying CD4 counts for approximately three years. Patients were divided into three groups: those who started with CD4s below 200, between 200 and 349, and 350 or higher.
Among patients starting therapy with CD4s above 200, the number of new cases (incidence) of peripheral neuropathy, anemia and kidney problems—and the risk for these complications—was lower, compared with those starting HIV treatment with CD4s below 200. The incidence and risks of kidney problems were similar among those starting therapy with CD4s above 350 versus 200 to 349, but the risk of peripheral neuropathy and anemia was found to be lower among those starting with 350 or more CD4s.
Dr. Lichtenstein’s group also reported that the incidence of each condition decreased rapidly and remained low the longer patients remained on ARV therapy. The risk of these complications occurring was actually highest during the first three months of treatment, regardless of the pre-therapy CD4 count.
Assessing a Failed AIDS Vaccine
After 20 years of defeat, it appeared that science may have finally developed a viable vaccine against AIDS. Merck's new drug, V520, was being tested in a huge clinical trial, involving 3,000 people in 15 cities, and it was widely considered the most promising new candidate in the field.
But last September, when Merck analyzed its initial trial data, it found that the vaccine had failed - and failed miserably. On Wednesday, the company issued its first report on the V520 trials, revealing that the drug did not protect against HIV, and more disturbingly, actually increased some people's susceptibility to the virus. "I don't think anyone imagined the results would be so definitively negative so quickly," says Dr. Gary Nabel, director of the Vaccine Research Center at the National Institutes of Health.
V520 may have failed, but somewhere in the details of the drug's nonsuccess, scientists hope to find insight into what will make future vaccines work. After all, V520 is just one of about 50 experimental HIV vaccines that are currently being tested in clinical trials, and almost all of them are designed to function the same way. While most vaccines expose the body to weakened or killed viruses, or pieces of them, to boost production of antibodies - proteins that recognize invading cells and flag them for destruction - that tack alone was too feeble to fend off HIV.
The new class of vaccines, including V520, takes a more direct route: They trigger cell-mediated immunity, which marshals killer T cells that both recognize and destroy viruses and bacteria, and can lead to a more robust, specific and longer-lived immune defense. It's not yet clear why V520 didn't work, but one theory involves its vector, or delivery vehicle. Like almost every other AIDS vaccine in development, Merck's drug used the common cold virus to transport its payload - three synthetic HIV genes - into the body's cells. What makes the adenovirus ideal for the task is precisely the reason colds make us so miserable - once inside a host, the cold virus infects cells and starts to replicate quickly.
The down side to that efficiency, however, is that cold viruses are so common that most people have developed a certain level of tolerance to them; if the adenovirus fails to excite the immune system, then any bugs piggybacked on the virus, such as HIV genes, will also slip past immune defenses. That's exactly what appears to have happened in the Merck trial: People with the highest pre-existing immunity to the common cold also had the highest rates of infection with HIV.
"It could be due to chance, or to differences in the populations we studied, or to something related to the vaccine itself," says Dr. Keith Gottesdiener, vice president of Vaccine and Infectious Disease Clinical Research at Merck. "The 'why' is still not well known.
" Researchers have already set about trying to figure it out. "We have to remember that Merck's was a single product testing a vaccine concept, which is that T cell immunity can protect against HIV infection," says Nabel. "And we know there are other ways to stimulate T cell immunity." Nabel is ready to test one such method, a vaccine similar to Merck's that uses different HIV genes and a "prime-boost" approach that involves two injections spaced a few months apart, instead of one shot, to maximize the stimulation of the body's T cells.
Other researchers, like Dr. David Ho, director of the Aaron Diamond AIDS Research Center in New York City and the recipient of a $25 million grant from the Gates Foundation to study novel vaccine strategies, think that the cold virus isn't the best way to deliver HIV. Ho is exploring the possibility that a different vector, such as the chicken pox virus, or perhaps no vector at all - simply injecting snippets of naked HIV DNA - could yield stronger immune responses.
At the International AIDS Vaccine Initiative (IAVI), a non-profit group of public and private partners focused on funding and accelerating AIDS vaccine research, scientists are studying the use of crippled, live strains of HIV - based on the success of other such live attenuated vaccines against polio and measles - which they think might be critical to waking up the right immune system defenses. "There is something magical about the replicating virus, because it has virtually its entire genome," says Dr. Seth Berkley, president of IAVI. His group is also investigating ways to stimulate so-called neutralizing antibodies, a special class of antibodies that appear to be able to defuse HIV.
Despite the ongoing study, experts argue that none of it will succeed without some basic changes in the way it's conducted. Most research occurs in isolation; there's little coordination among labs and no network through which data can be shared, making it difficult for scientists to learn from each other's missteps. Worse, it takes years to get regulatory approval to start a human trial for a new vaccine - not to mention enrolling the volunteers and training the right personnel - so, by the time experiments get underway, the science around which the vaccine was built has long since become outdated. "The trials are not informing science at the moment," says Dr. Alan Bernstein, executive director of the Global HIV Vaccine Enterprise, an alliance of independent organizations dedicated to accelerating HIV vaccine research. "Science - and vaccine development - is an iterative process, except that in HIV vaccine research, there isn't a lot of iteration going on."
The Enterprise, which was founded in 2005, intends to change that. With funding from the Gates Foundation, Wellcome Trust, National Institutes of Health and the European Union, it will serve as a hub for guiding worldwide HIV vaccine research. We want to ensure that the trials are done faster, better and smarter, says Bernstein. And hopefully, with more success. [TM]
But last September, when Merck analyzed its initial trial data, it found that the vaccine had failed - and failed miserably. On Wednesday, the company issued its first report on the V520 trials, revealing that the drug did not protect against HIV, and more disturbingly, actually increased some people's susceptibility to the virus. "I don't think anyone imagined the results would be so definitively negative so quickly," says Dr. Gary Nabel, director of the Vaccine Research Center at the National Institutes of Health.
V520 may have failed, but somewhere in the details of the drug's nonsuccess, scientists hope to find insight into what will make future vaccines work. After all, V520 is just one of about 50 experimental HIV vaccines that are currently being tested in clinical trials, and almost all of them are designed to function the same way. While most vaccines expose the body to weakened or killed viruses, or pieces of them, to boost production of antibodies - proteins that recognize invading cells and flag them for destruction - that tack alone was too feeble to fend off HIV.
The new class of vaccines, including V520, takes a more direct route: They trigger cell-mediated immunity, which marshals killer T cells that both recognize and destroy viruses and bacteria, and can lead to a more robust, specific and longer-lived immune defense. It's not yet clear why V520 didn't work, but one theory involves its vector, or delivery vehicle. Like almost every other AIDS vaccine in development, Merck's drug used the common cold virus to transport its payload - three synthetic HIV genes - into the body's cells. What makes the adenovirus ideal for the task is precisely the reason colds make us so miserable - once inside a host, the cold virus infects cells and starts to replicate quickly.
The down side to that efficiency, however, is that cold viruses are so common that most people have developed a certain level of tolerance to them; if the adenovirus fails to excite the immune system, then any bugs piggybacked on the virus, such as HIV genes, will also slip past immune defenses. That's exactly what appears to have happened in the Merck trial: People with the highest pre-existing immunity to the common cold also had the highest rates of infection with HIV.
"It could be due to chance, or to differences in the populations we studied, or to something related to the vaccine itself," says Dr. Keith Gottesdiener, vice president of Vaccine and Infectious Disease Clinical Research at Merck. "The 'why' is still not well known.
" Researchers have already set about trying to figure it out. "We have to remember that Merck's was a single product testing a vaccine concept, which is that T cell immunity can protect against HIV infection," says Nabel. "And we know there are other ways to stimulate T cell immunity." Nabel is ready to test one such method, a vaccine similar to Merck's that uses different HIV genes and a "prime-boost" approach that involves two injections spaced a few months apart, instead of one shot, to maximize the stimulation of the body's T cells.
Other researchers, like Dr. David Ho, director of the Aaron Diamond AIDS Research Center in New York City and the recipient of a $25 million grant from the Gates Foundation to study novel vaccine strategies, think that the cold virus isn't the best way to deliver HIV. Ho is exploring the possibility that a different vector, such as the chicken pox virus, or perhaps no vector at all - simply injecting snippets of naked HIV DNA - could yield stronger immune responses.
At the International AIDS Vaccine Initiative (IAVI), a non-profit group of public and private partners focused on funding and accelerating AIDS vaccine research, scientists are studying the use of crippled, live strains of HIV - based on the success of other such live attenuated vaccines against polio and measles - which they think might be critical to waking up the right immune system defenses. "There is something magical about the replicating virus, because it has virtually its entire genome," says Dr. Seth Berkley, president of IAVI. His group is also investigating ways to stimulate so-called neutralizing antibodies, a special class of antibodies that appear to be able to defuse HIV.
Despite the ongoing study, experts argue that none of it will succeed without some basic changes in the way it's conducted. Most research occurs in isolation; there's little coordination among labs and no network through which data can be shared, making it difficult for scientists to learn from each other's missteps. Worse, it takes years to get regulatory approval to start a human trial for a new vaccine - not to mention enrolling the volunteers and training the right personnel - so, by the time experiments get underway, the science around which the vaccine was built has long since become outdated. "The trials are not informing science at the moment," says Dr. Alan Bernstein, executive director of the Global HIV Vaccine Enterprise, an alliance of independent organizations dedicated to accelerating HIV vaccine research. "Science - and vaccine development - is an iterative process, except that in HIV vaccine research, there isn't a lot of iteration going on."
The Enterprise, which was founded in 2005, intends to change that. With funding from the Gates Foundation, Wellcome Trust, National Institutes of Health and the European Union, it will serve as a hub for guiding worldwide HIV vaccine research. We want to ensure that the trials are done faster, better and smarter, says Bernstein. And hopefully, with more success. [TM]
Wednesday 31 October 2007
Asian Diet: Nutrition key to surviving HIV/AIDS, WHO says
Bangkok - Well-balanced meals are a key ingredient to survival forthe millions of HIV/AIDS patients in South and South-East Asia, WorldHealth Organization (WHO) experts said Tuesday.
"Nutrition and HIVare closely related," said Samlee Plianbangchang, WHO's regionaldirector for South-East Asia."HIV affects nutritional status, and poor nutrition in turn leads tofaster progression of HIV to AIDS," Samlee told a seminar of healthworkers and experts who gathered in Bangkok this week to findsolutions to fighting the two epidemics of malnutrition andHIV/AIDS. "Scaling-up care and antiretroviral therapy cannot beaddressed without appropriate support for nutrition.
"There are an estimated 4 million people suffering from HIV/AIDS inBangladesh, Bhutan, India, Indonesia, Nepal, Myanmar, Thailand, SouthKorea and Sri Lanka, the area defined by the UN agency as South-EastAsia.The good news is that most Asian diets are well-suited to providingthe nutrition HIV/AIDS patients require."I think Thai food is well-balanced and has all the nutrientssomebody needs, but it depends on keeping the right balance of carbohydrates, proteins and fats," said Ranga Saadeh, a scientist working for WHO's nutrition department in Geneva.Evidence has established that people living with HIV have higher energy needs than those who are HIV-negative.
Asymptomatic HIV-positive adults or children need 10 per cent more energy than those who are not HIV-positive, and those at advanced stages need 20 to 30 per cent more energy to maintain body weight,Saadeh said.HIV-positive children who are losing weight need 50 to 100 per centmore energy, she said. Providing a balanced, nutritious diet in countries where malnutritionis endemic poses an added challenge to their health services.
"This HIV/AIDs epidemic is being superimposed on the already existing malnutrition problems," Saddeh said, "so if we want to make a difference, we should really deal with both challenges at the sametime.
"http://www.earthtimes.org/articles/show/121064.html
"Nutrition and HIVare closely related," said Samlee Plianbangchang, WHO's regionaldirector for South-East Asia."HIV affects nutritional status, and poor nutrition in turn leads tofaster progression of HIV to AIDS," Samlee told a seminar of healthworkers and experts who gathered in Bangkok this week to findsolutions to fighting the two epidemics of malnutrition andHIV/AIDS. "Scaling-up care and antiretroviral therapy cannot beaddressed without appropriate support for nutrition.
"There are an estimated 4 million people suffering from HIV/AIDS inBangladesh, Bhutan, India, Indonesia, Nepal, Myanmar, Thailand, SouthKorea and Sri Lanka, the area defined by the UN agency as South-EastAsia.The good news is that most Asian diets are well-suited to providingthe nutrition HIV/AIDS patients require."I think Thai food is well-balanced and has all the nutrientssomebody needs, but it depends on keeping the right balance of carbohydrates, proteins and fats," said Ranga Saadeh, a scientist working for WHO's nutrition department in Geneva.Evidence has established that people living with HIV have higher energy needs than those who are HIV-negative.
Asymptomatic HIV-positive adults or children need 10 per cent more energy than those who are not HIV-positive, and those at advanced stages need 20 to 30 per cent more energy to maintain body weight,Saadeh said.HIV-positive children who are losing weight need 50 to 100 per centmore energy, she said. Providing a balanced, nutritious diet in countries where malnutritionis endemic poses an added challenge to their health services.
"This HIV/AIDs epidemic is being superimposed on the already existing malnutrition problems," Saddeh said, "so if we want to make a difference, we should really deal with both challenges at the sametime.
"http://www.earthtimes.org/articles/show/121064.html
Saturday 27 October 2007
"Impact of AIDS on children remains under-researched and poorly
(Speech Check against Delivery) Dr Peter Piot UNAIDS Executive
Director's speech at the JOINT LEARNING INITIATIVE ON CHILDREN AND HIV/AIDS: International Symposium. Harvard Medical School. 24 September 2007.
I first want to thank Jim Kim, Peter Bell, Agnes Binagwaho for
inviting me here today, and to pay tribute to the tremendous work
they – and all of you – are doing. It is a privilege to be here today
with so many experts and activists. The issue of children and AIDS
was overlooked for far too long. UNAIDS was one of the first to
welcome the creation of the Joint Learning Initiative on Children and
AIDS, and I look forward to hearing about the progress you've made.
Let's start by looking at progress on AIDS in general. It's a mixed
picture, but there definitely is progress.
Today, 2.5 million people in developing countries are taking anti-
retroviral treatment up from 100,000 in 2001.
And in some populations in East Africa, the Caribbean, and Asia, HIV
infections are falling.
But if HIV is declining in some populations, it is rising in others.
In some Asian countries there's an upsurge in HIV infections among
men who have sex with men, but infections are declining in other
groups. The most striking overall increases have taken place in East
Asia, Eastern Europe, and Central Asia: the number of people
living with HIV went up by one fifth here between 2004 and 2006.
Globally, young people (15-24) accounted for 40% of new HIV
infections last year.
One in seven new HIV infections last year occurred among under-
fifteens. By the end of 2006, 2.3 million (1.7-3.5 million) children
(under 15) were living with HIV.
Let's just remind ourselves that the United Nations Convention on the
Rights of the Child defines children as people up to the age of 18.
But AIDS epidemiologists compile information for under fifteens and
for 15-24-year-olds. Lack of disaggregated data for children makes it
even harder to take effective action on their behalf.
One reason for this is the feminization of the epidemic: almost half
of all adults living with HIV are women. Only one in ten pregnant
women with HIV in low and middleincome countries receives anti-
retroviral prophylaxis to prevent transmission of HIV to their
children. Every year, more than 500,000 children are infected via
transmission from their mothers.
But this is just one way children become infected with HIV. Sexual
abuse is another.
The second (and main) way is through sex – whether it's between young
girls and older men, sex between adolescents, or sex between
trafficked girls or boys and clients, sexual violence and rape, or
incest.
A third cause of infection is injecting drug use, which often starts
in adolescence. In Russia, 76% of all people living with HIV are or
have been injecting drug users.
This is all fuelled by ignorance about HIV transmission. It's amazing
how prevalent this still is in 2007. I've just come back from China
where most young people have barely a clue about how HIV is
transmitted.
At the same time, only one in ten children needing HIV treatment can
get it – even though paediatric drug formulations are much more
widely available, and the price of antiretroviral drugs for children
has dropped – in some cases to less than 16 US cents per day. Just 4%
of children born to HIV-positive mothers receive cotrimoxazole, which
WHO recommends providing to children when early diagnosis of HIV
infection is unavailable. In Botswana and Zimbabwe, child mortality
rates have nearly doubled since 1990.
Last eek UNICEF reported some remarkable declines in child mortality
throughout the world, for the first time fewer than 10 million
children under five died – except in countries with high HIV
prevalence and those in conflict.
More than 15 million children worldwide have now been orphaned by
AIDS – over 12 million in Southern and East Africa. Orphan
populations are increasing in some populations in Asia, Latin America
and the Caribbean, and Eastern Europe too.
This much we know. Now let me turn to what we don't know.
We are constantly striving to know more about the AIDS epidemic,
through better and more accurate data collection. But there's still a
long way to go.
Today's surveillance categories are too broad and too blurred.
Collecting data for children up to the age of 15 and then for young
people between the ages of 15 and 24 doesn't give us the sort of
information we need: there's a huge difference in terms
of action between HIV infection at 15 and acquiring HIV at 24.
We need much more refined data about different age groups. We also
need to distinguish between the different categories of orphan –
"double", "one parent", maternal and paternal. And we need to become
much more systematic in pinpointing the differences between epidemics
within countries.
We also need to re-evaluate the way we perceive the issue of children
and AIDS. As so often happens, we have tended to only do this through
the medical lens, with a primary focus on mother to child
transmission. But this is to over-simplify, and to
ignore critical social and rights-related issues.
One problem is that we don't know enough about what these issues are.
We sense that AIDS is breaking up families and communities and
challenging traditional safety nets. We know that the impact on
household welfare is greater on the poor than on the better off, and
that gender inequities make girls more vulnerable than boys. We
are aware that it is threatening children's rights - civil,
political, economic, social and cultural.
And then there's the new reality: older children living with HIV. In
recent years, I've been meeting increasing numbers of HIV positive
adolescents and young adults.
But we often still lack hard, empirical data: the impact of AIDS on
children remains under-researched and poorly understood. We simply
don't know enough about what is happening. That's why the Joint
Learning Initiative is so badly needed.
Now let's look at what action is being taken today.
It's nearly 20 years since world leaders decided that people under 18
needed their own convention. That convention - the 1989 United
Nations Convention on the Rights of the Child, famously ratified by
all UN Member States except the US and Somalia – stresses the
importance of making the "best interests of the child" a
primary consideration and lists a series of rights. These include
such basics as information, education, non-discrimination, health,
social security, an appropriate standard of living, to be protected
from violence and different forms of exploitation, and the right not
to be separated from their parents. All are critical if children are
to grow up to live safe and healthy lives in a world with AIDS.
Since then, a series of international meetings and declarations have
highlighted the urgent need to address the issue of children and
AIDS. But to what extent are these declarations being acted on?
A few countries have substantially increased access to services to
prevent transmission of HIV from parents to children. For example, in
Argentina, Botswana, Jamaica, and Ukraine, more than 85% of HIV-
positive pregnant women received antiretroviral drugs to prevent
transmission of HIV to their children.
Some countries - including Botswana, Rwanda, and Thailand - have
scaled up HIV treatment for children by integrating it into treatment
sites for adults. Thailand is getting antiretrovirals to more than
95% of the under-15s in need.
Several countries in southern Africa have provided child grants and
other benefits on a national scale. Kenya, Malawi and Mozambique have
piloted cash-transfer programmes in poor areas.
In 58 countries surveyed last year, 74% of primary schools and 81% of
secondary schools said they were providing AIDS education. This is
critical if adolescents are to protect themselves from infection. To
be effective, AIDS education must fulfil the right to information (as
required in the Convention on the Rights of the Child). It must
provide information about all risks, and offer a broad palette of
prevention options – including abstinence, condoms, and measures to
address inequalities between girls and boys.
More efforts are being made to see that children get a fair share of
AIDS funding. A number of donors including the US and UK have
earmarked at least 10% of their AIDS money to go towards services
for children.
And lastly, more is being done to integrate services – to forge links
across diseases and sectors and bring partners closer together. In
Kenya, Rwanda, Tanzania and Zambia, strategic investment of AIDS
funding is improving services such as immunization and antenatal
care. And Norway's Women and Children First Initiative sets out to
provide a continuum of care for mothers, newborns, and children.
Many organizations are providing support to help countries look after
their children better. UNAIDS co-sponsor UNICEF, for example, has
made tackling children and AIDS one of its top priorities.
In 2005, UNAIDS joined UNICEF to launch "Unite For Children, Unite
Against AIDS", which sets targets for scaling up "The Four Ps":
prevention of HIV transmission from mother to child, paediatric
treatment for HIV, prevention of HIV among adolescents and young
people, and protection and support for children affected by HIV.
And as Peter mentioned earlier, civil society groups –the Elizabeth
Glaser Paediatric Foundation, the Ecumenical Advocacy Alliance and,
of course, the Francois-Xavier Bagnoud Association – are doing
tremendous work.
But most importantly of all, communities are responding and adapting
to the new realities around children and AIDS – often with tremendous
resilience.
So how do we build on this progress and intensify its impact?
We're here today because there are no simple answers to these
questions.
AIDS, as many of you have heard me say before, is an exceptional
issue – in terms of its threat to humanity and its complexity. The
Joint Learning Initiative was itself born out of recognition that the
issue of children and AIDS is immensely complex – and that it
requires a complex response.
I would like to suggest seven elements that I regard as key to making
that response effective.
First, it must be firmly grounded in human rights principles – in
line with the 2003 Comment on the Convention on the Rights of the
Child that "the child should be placed at the centre of the response
to the pandemic, and strategies should be adapted to children's
rights and needs". To be effective, those strategies have to
work equally well for seven-year-olds as seventeen-year-olds.
Second, it must involve a wide range of actors – not least the
children concerned, their parents, grandparents, and members of the
communities they live in. This means bringing children and family
members – including those living with HIV - to the table when
programmes are designed.
Third, it must prevent new HIV infections – for example by scaling up
access to services to prevent mother to child transmission and by
making HIV prevention more available and accessible to adolescents.
By addressing vulnerability and – though I know this is
controversial – by preventing sexual transmission. Universal Access to
HIV prevention, treatment, care and support is not only for adults!
Fourth, it must provide treatment for children. This will mean
scaling up testing and counseling, and making antiretroviral drugs
and cotrimoxazole more easily available.
Fifth, it must provide adequate levels of social welfare to children
infected and affected by HIV, and to their families and communities –
for example through cash transfers.
Sixth, it must be fully funded at international and national level.
This means more money for children and AIDS from international donors
and a higher priority for children in national development plans. At
UNAIDS, we estimate that $2.7 billion will be needed for programmes
for orphans and vulnerable children in 2008.
And finally, as I mentioned earlier, it must be based on more
accurate information.
This means not just improving surveillance but also clarifying how
children become vulnerable, looking more closely at socio-economic
contexts, and intensifying research into psychosocial impacts and
responses. It means looking at children in the contexts of their
families and communities, improving monitoring and evaluation
systems, studying how households cope and what local care-giving
practices involve.
To turn this wish-list into reality, high levels of political will
and commitment will be required. To inform and drive the process
forward, we will need a growing body of knowledge about children and
AIDS. We will need evidence from successful
interventions to show what can be done. And we will need sustained
activism to make sure the right action is taken – now and in the
years to come.
This brings me to my conclusion: it is time now to bite the bullet
and start thinking and acting in the context of the longer term –
something we have repeatedly failed to do up to now. Here, children
clearly have a major role to play.
We need to be confident that what we are doing now works on two
levels – both now and in the years to come. We must take steps now so
a girl born today doesn't grow up to produce an HIV positive baby and
so children born with HIV get anti-retroviral treatment and live
longer, healthier lives.
This means doing what you are doing in the Joint Initiative: taking a
long, hard look at what we are doing, identifying what works and
coming up with new approaches and new research to address new trends.
It means working together in a coherent fashion, on long-term,
integrated programmes: the day of the short-term, ad-hoc project is
over.
And it means ensuring that our response is comprehensive, flexible
and anticipatory - tailored to different epidemics and ready to
change as epidemics evolve: AIDS doesn't stand still, and the world
around it is not standing still - nor can we.
Thank you.
http://www.jlica.shuttlepod.org/Default.aspx?pageId=27417
Director's speech at the JOINT LEARNING INITIATIVE ON CHILDREN AND HIV/AIDS: International Symposium. Harvard Medical School. 24 September 2007.
I first want to thank Jim Kim, Peter Bell, Agnes Binagwaho for
inviting me here today, and to pay tribute to the tremendous work
they – and all of you – are doing. It is a privilege to be here today
with so many experts and activists. The issue of children and AIDS
was overlooked for far too long. UNAIDS was one of the first to
welcome the creation of the Joint Learning Initiative on Children and
AIDS, and I look forward to hearing about the progress you've made.
Let's start by looking at progress on AIDS in general. It's a mixed
picture, but there definitely is progress.
Today, 2.5 million people in developing countries are taking anti-
retroviral treatment up from 100,000 in 2001.
And in some populations in East Africa, the Caribbean, and Asia, HIV
infections are falling.
But if HIV is declining in some populations, it is rising in others.
In some Asian countries there's an upsurge in HIV infections among
men who have sex with men, but infections are declining in other
groups. The most striking overall increases have taken place in East
Asia, Eastern Europe, and Central Asia: the number of people
living with HIV went up by one fifth here between 2004 and 2006.
Globally, young people (15-24) accounted for 40% of new HIV
infections last year.
One in seven new HIV infections last year occurred among under-
fifteens. By the end of 2006, 2.3 million (1.7-3.5 million) children
(under 15) were living with HIV.
Let's just remind ourselves that the United Nations Convention on the
Rights of the Child defines children as people up to the age of 18.
But AIDS epidemiologists compile information for under fifteens and
for 15-24-year-olds. Lack of disaggregated data for children makes it
even harder to take effective action on their behalf.
One reason for this is the feminization of the epidemic: almost half
of all adults living with HIV are women. Only one in ten pregnant
women with HIV in low and middleincome countries receives anti-
retroviral prophylaxis to prevent transmission of HIV to their
children. Every year, more than 500,000 children are infected via
transmission from their mothers.
But this is just one way children become infected with HIV. Sexual
abuse is another.
The second (and main) way is through sex – whether it's between young
girls and older men, sex between adolescents, or sex between
trafficked girls or boys and clients, sexual violence and rape, or
incest.
A third cause of infection is injecting drug use, which often starts
in adolescence. In Russia, 76% of all people living with HIV are or
have been injecting drug users.
This is all fuelled by ignorance about HIV transmission. It's amazing
how prevalent this still is in 2007. I've just come back from China
where most young people have barely a clue about how HIV is
transmitted.
At the same time, only one in ten children needing HIV treatment can
get it – even though paediatric drug formulations are much more
widely available, and the price of antiretroviral drugs for children
has dropped – in some cases to less than 16 US cents per day. Just 4%
of children born to HIV-positive mothers receive cotrimoxazole, which
WHO recommends providing to children when early diagnosis of HIV
infection is unavailable. In Botswana and Zimbabwe, child mortality
rates have nearly doubled since 1990.
Last eek UNICEF reported some remarkable declines in child mortality
throughout the world, for the first time fewer than 10 million
children under five died – except in countries with high HIV
prevalence and those in conflict.
More than 15 million children worldwide have now been orphaned by
AIDS – over 12 million in Southern and East Africa. Orphan
populations are increasing in some populations in Asia, Latin America
and the Caribbean, and Eastern Europe too.
This much we know. Now let me turn to what we don't know.
We are constantly striving to know more about the AIDS epidemic,
through better and more accurate data collection. But there's still a
long way to go.
Today's surveillance categories are too broad and too blurred.
Collecting data for children up to the age of 15 and then for young
people between the ages of 15 and 24 doesn't give us the sort of
information we need: there's a huge difference in terms
of action between HIV infection at 15 and acquiring HIV at 24.
We need much more refined data about different age groups. We also
need to distinguish between the different categories of orphan –
"double", "one parent", maternal and paternal. And we need to become
much more systematic in pinpointing the differences between epidemics
within countries.
We also need to re-evaluate the way we perceive the issue of children
and AIDS. As so often happens, we have tended to only do this through
the medical lens, with a primary focus on mother to child
transmission. But this is to over-simplify, and to
ignore critical social and rights-related issues.
One problem is that we don't know enough about what these issues are.
We sense that AIDS is breaking up families and communities and
challenging traditional safety nets. We know that the impact on
household welfare is greater on the poor than on the better off, and
that gender inequities make girls more vulnerable than boys. We
are aware that it is threatening children's rights - civil,
political, economic, social and cultural.
And then there's the new reality: older children living with HIV. In
recent years, I've been meeting increasing numbers of HIV positive
adolescents and young adults.
But we often still lack hard, empirical data: the impact of AIDS on
children remains under-researched and poorly understood. We simply
don't know enough about what is happening. That's why the Joint
Learning Initiative is so badly needed.
Now let's look at what action is being taken today.
It's nearly 20 years since world leaders decided that people under 18
needed their own convention. That convention - the 1989 United
Nations Convention on the Rights of the Child, famously ratified by
all UN Member States except the US and Somalia – stresses the
importance of making the "best interests of the child" a
primary consideration and lists a series of rights. These include
such basics as information, education, non-discrimination, health,
social security, an appropriate standard of living, to be protected
from violence and different forms of exploitation, and the right not
to be separated from their parents. All are critical if children are
to grow up to live safe and healthy lives in a world with AIDS.
Since then, a series of international meetings and declarations have
highlighted the urgent need to address the issue of children and
AIDS. But to what extent are these declarations being acted on?
A few countries have substantially increased access to services to
prevent transmission of HIV from parents to children. For example, in
Argentina, Botswana, Jamaica, and Ukraine, more than 85% of HIV-
positive pregnant women received antiretroviral drugs to prevent
transmission of HIV to their children.
Some countries - including Botswana, Rwanda, and Thailand - have
scaled up HIV treatment for children by integrating it into treatment
sites for adults. Thailand is getting antiretrovirals to more than
95% of the under-15s in need.
Several countries in southern Africa have provided child grants and
other benefits on a national scale. Kenya, Malawi and Mozambique have
piloted cash-transfer programmes in poor areas.
In 58 countries surveyed last year, 74% of primary schools and 81% of
secondary schools said they were providing AIDS education. This is
critical if adolescents are to protect themselves from infection. To
be effective, AIDS education must fulfil the right to information (as
required in the Convention on the Rights of the Child). It must
provide information about all risks, and offer a broad palette of
prevention options – including abstinence, condoms, and measures to
address inequalities between girls and boys.
More efforts are being made to see that children get a fair share of
AIDS funding. A number of donors including the US and UK have
earmarked at least 10% of their AIDS money to go towards services
for children.
And lastly, more is being done to integrate services – to forge links
across diseases and sectors and bring partners closer together. In
Kenya, Rwanda, Tanzania and Zambia, strategic investment of AIDS
funding is improving services such as immunization and antenatal
care. And Norway's Women and Children First Initiative sets out to
provide a continuum of care for mothers, newborns, and children.
Many organizations are providing support to help countries look after
their children better. UNAIDS co-sponsor UNICEF, for example, has
made tackling children and AIDS one of its top priorities.
In 2005, UNAIDS joined UNICEF to launch "Unite For Children, Unite
Against AIDS", which sets targets for scaling up "The Four Ps":
prevention of HIV transmission from mother to child, paediatric
treatment for HIV, prevention of HIV among adolescents and young
people, and protection and support for children affected by HIV.
And as Peter mentioned earlier, civil society groups –the Elizabeth
Glaser Paediatric Foundation, the Ecumenical Advocacy Alliance and,
of course, the Francois-Xavier Bagnoud Association – are doing
tremendous work.
But most importantly of all, communities are responding and adapting
to the new realities around children and AIDS – often with tremendous
resilience.
So how do we build on this progress and intensify its impact?
We're here today because there are no simple answers to these
questions.
AIDS, as many of you have heard me say before, is an exceptional
issue – in terms of its threat to humanity and its complexity. The
Joint Learning Initiative was itself born out of recognition that the
issue of children and AIDS is immensely complex – and that it
requires a complex response.
I would like to suggest seven elements that I regard as key to making
that response effective.
First, it must be firmly grounded in human rights principles – in
line with the 2003 Comment on the Convention on the Rights of the
Child that "the child should be placed at the centre of the response
to the pandemic, and strategies should be adapted to children's
rights and needs". To be effective, those strategies have to
work equally well for seven-year-olds as seventeen-year-olds.
Second, it must involve a wide range of actors – not least the
children concerned, their parents, grandparents, and members of the
communities they live in. This means bringing children and family
members – including those living with HIV - to the table when
programmes are designed.
Third, it must prevent new HIV infections – for example by scaling up
access to services to prevent mother to child transmission and by
making HIV prevention more available and accessible to adolescents.
By addressing vulnerability and – though I know this is
controversial – by preventing sexual transmission. Universal Access to
HIV prevention, treatment, care and support is not only for adults!
Fourth, it must provide treatment for children. This will mean
scaling up testing and counseling, and making antiretroviral drugs
and cotrimoxazole more easily available.
Fifth, it must provide adequate levels of social welfare to children
infected and affected by HIV, and to their families and communities –
for example through cash transfers.
Sixth, it must be fully funded at international and national level.
This means more money for children and AIDS from international donors
and a higher priority for children in national development plans. At
UNAIDS, we estimate that $2.7 billion will be needed for programmes
for orphans and vulnerable children in 2008.
And finally, as I mentioned earlier, it must be based on more
accurate information.
This means not just improving surveillance but also clarifying how
children become vulnerable, looking more closely at socio-economic
contexts, and intensifying research into psychosocial impacts and
responses. It means looking at children in the contexts of their
families and communities, improving monitoring and evaluation
systems, studying how households cope and what local care-giving
practices involve.
To turn this wish-list into reality, high levels of political will
and commitment will be required. To inform and drive the process
forward, we will need a growing body of knowledge about children and
AIDS. We will need evidence from successful
interventions to show what can be done. And we will need sustained
activism to make sure the right action is taken – now and in the
years to come.
This brings me to my conclusion: it is time now to bite the bullet
and start thinking and acting in the context of the longer term –
something we have repeatedly failed to do up to now. Here, children
clearly have a major role to play.
We need to be confident that what we are doing now works on two
levels – both now and in the years to come. We must take steps now so
a girl born today doesn't grow up to produce an HIV positive baby and
so children born with HIV get anti-retroviral treatment and live
longer, healthier lives.
This means doing what you are doing in the Joint Initiative: taking a
long, hard look at what we are doing, identifying what works and
coming up with new approaches and new research to address new trends.
It means working together in a coherent fashion, on long-term,
integrated programmes: the day of the short-term, ad-hoc project is
over.
And it means ensuring that our response is comprehensive, flexible
and anticipatory - tailored to different epidemics and ready to
change as epidemics evolve: AIDS doesn't stand still, and the world
around it is not standing still - nor can we.
Thank you.
http://www.jlica.shuttlepod.org/Default.aspx?pageId=27417
Monday 1 October 2007
Racism hits non-English speakers' health
Published in Aids_Asia Mailing List, September 17, 2007
Racial discrimination is putting at risk the mental health of manyVictorians, a new government report has found.
The VicHealth report, More Than Tolerance: Embracing Diversity ForHealth, was based on a survey of more than 4,000 people.
It found almost two-in-five Victorians from non-English speakingbackgrounds reported they had been treated with disrespect, insultedor called names because of their ethnicity, with a small proportionof those saying they experienced discrimination often.
Of those who reported racial discrimination, 40 per cent said theysuffered discrimination at work, while 30 per cent were discriminatedagainst in an educational setting, the report said.Almost 45 per cent said they had a bad experience with racism at asporting or public event, while 19 per cent said they experiencedracism at the hands of police.
About one-third of Victorians said they could identify cultural orethnic groups they believed did not fit into Australian society.
The report revealed that those who suffered discrimination were morelikely to suffer poor mental health, smoke and misuse drugs oralcohol.
The findings tally with previous studies that showed an associationbetween discrimination and heart disease, diabetes and low infantbirth rate, VicHealth chief executive Todd Harper said.
People from migrant and refugee backgrounds continued tosuffer "unacceptably high levels of discrimination, in turn affectingtheir health and well-being", he said.
Former Australian Medical Association president Dr Mukesh Haikerwal,who is a GP in Melbourne's west, and who will help launch the report,said the report found a strong connection between racism and poormental health.
"The results of discrimination are a feeling of greater isolation andfeeling less connected with society," he said."That isolation and the very fact that they are racially abused means that they suffer ill-health including mental illness.
"We see this all the time in the west, of course, that people are newto the country, having trouble with the language and setting into anew life."They feel very upset and very much under the gun because of whattheir perceive as discrimination and poor support.
"Mr Harper said while the statistics on racism were striking, therewas also good news in the report."About 90 per cent of Victorian agreed that it was good to have asociety made up of different cultures, so I think that there is afair bit of support that we can build upon here," he said.
The report recommends a range of interventions, including furtherstudies, a range of communication and education campaigns andcommunity development programs to build networks between groups andcommunities.http://au.news.yahoo.com/070916/2/14ftb.html?=mvhttp://www.vichealth.vic.gov.au/discrimattitudes/
Racial discrimination is putting at risk the mental health of manyVictorians, a new government report has found.
The VicHealth report, More Than Tolerance: Embracing Diversity ForHealth, was based on a survey of more than 4,000 people.
It found almost two-in-five Victorians from non-English speakingbackgrounds reported they had been treated with disrespect, insultedor called names because of their ethnicity, with a small proportionof those saying they experienced discrimination often.
Of those who reported racial discrimination, 40 per cent said theysuffered discrimination at work, while 30 per cent were discriminatedagainst in an educational setting, the report said.Almost 45 per cent said they had a bad experience with racism at asporting or public event, while 19 per cent said they experiencedracism at the hands of police.
About one-third of Victorians said they could identify cultural orethnic groups they believed did not fit into Australian society.
The report revealed that those who suffered discrimination were morelikely to suffer poor mental health, smoke and misuse drugs oralcohol.
The findings tally with previous studies that showed an associationbetween discrimination and heart disease, diabetes and low infantbirth rate, VicHealth chief executive Todd Harper said.
People from migrant and refugee backgrounds continued tosuffer "unacceptably high levels of discrimination, in turn affectingtheir health and well-being", he said.
Former Australian Medical Association president Dr Mukesh Haikerwal,who is a GP in Melbourne's west, and who will help launch the report,said the report found a strong connection between racism and poormental health.
"The results of discrimination are a feeling of greater isolation andfeeling less connected with society," he said."That isolation and the very fact that they are racially abused means that they suffer ill-health including mental illness.
"We see this all the time in the west, of course, that people are newto the country, having trouble with the language and setting into anew life."They feel very upset and very much under the gun because of whattheir perceive as discrimination and poor support.
"Mr Harper said while the statistics on racism were striking, therewas also good news in the report."About 90 per cent of Victorian agreed that it was good to have asociety made up of different cultures, so I think that there is afair bit of support that we can build upon here," he said.
The report recommends a range of interventions, including furtherstudies, a range of communication and education campaigns andcommunity development programs to build networks between groups andcommunities.http://au.news.yahoo.com/070916/2/14ftb.html?=mvhttp://www.vichealth.vic.gov.au/discrimattitudes/
Asia's fishermen at risk for unwanted catch: HIV
BALI, Indonesia (AP) — In appearance, they couldn't be more different.Ririn, with her warm brown skin and plump face, simply glows. Youngand sweet, just two months after giving birth to a baby girl.
Edi stands out as the roughest in a circle of men on the fishingdock. Streaks of motor oil mix with sweat on his chest and weather-beaten face as he puffs on a cigarette and talks loudly, not caringthat his frayed cutoffs are unzipped.
The two are part of an expanding nexus that's spreading HIV and AIDS.He's a deep-sea fishermen who spends his short time ashore prowlingfor sex; she's a woman in port who gets paid to provide a warm body.Bali is a famed tourist playground, but there's a side to the islandmost foreign visitors never see. Indonesian fishermen who oftenhaven't seen land for months put in at Benoa Harbour and makestraight for the closest bar with two things in mind: getting drunkand finding women.
These habits have put fishermen at high risk of getting HIV or AIDS -especially in Asia, because it's home to 2.5 million fishermen, orabout 85 per cent of the world's total. Yet fishermen have beenlargely overlooked since the virus began raging 21 years ago, withonly a handful of surveys focusing on them.
One report found that out of 10 poor countries, all but one hadfishermen with HIV rates four to 14 times higher than the generalpopulation.
Two studies of fishermen on big commercial vessels found over 15 percent were HIV-positive in Thai and Cambodian ports. That's more thanfive times the rate of other migrants at high risk for infection,such as truck drivers.A few programs in Papua New Guinea, Thailand and elsewhere in theregion are now working to reach fishermen, and the UN Food andAgriculture Organization earlier this year urged that they berecognized as high risk. But fishermen weren't even mentioned inUNAIDS' 630-page 2006 global report.
"I don't think there's been much targeting of treatment and healthservice availability," says Edward Allison, of The WorldFish Centerin Malaysia, who has researched HIV in fishermen.
The bulk of Asia's fishermen are small-scale operators who return tohome port frequently or stop at coastal fishing camps where women andbooze are readily available. Others work aboard bigger vessels formonths at a time.In Bali, most of the fishermen are bachelors in their 20s and 30sfrom Indonesia's main island of Java. Many come from conservativeMuslim farm families but have traded their traditions for a cultureof danger and machismo.
Some return to home port in Bali at voyage's end. Others fish wellbeyond native waters, docking as far away as South Africa, Sri Lanka,Spain and Panama. Either way, their pockets are filled with money andthe only women waiting ashore are those looking to get paid.
Ririn, who like many Indonesians uses only one name, grew up on arice farm with her parents and seven siblings on the island of Java.She dropped out of school in fifth grade.At 20, she was offered a chance for a better life, working as a maidon Bali, a neighbouring island she imagined was full of hope andmoney."I wanted to help my family back home," she says. "There's a lot ofmouths to feed."But after three months of cooking, cleaning and caring for someoneelse's children, she had only US$20.
Like many young women far from home, she was wooed by a man promising$40 to $50 a month for fewer hours. She would only do it for a littlewhile, she thought. Just long enough to save up for a small businessof her own.After six months as a prostitute, she learned about HIV - when shetested positive. She kept working until her sixth month of pregnancy.
There are no condom machines or AIDS outreach workers on the crowdedwharf in Bali. Some fishermen say they've had a disease "down there"or know someone who has, but many are convinced that certain women,mostly Indonesians, are free of HIV."This area is very safe," fisherman Herman Shokana said above theroar of boat engines. "But when we go abroad, we'll probably get it.
"Most sailors infected with STDs treat themselves with cheapantibiotics. They may take the wrong dose or stop treatment whensymptoms disappear, allowing STDs to linger, which makes it easier tocontract HIV. They also are misled by greedy peddlers.
"When the ships come in, medicine vendors or peddlers are alreadywaiting for them," said Made Setiawan, a doctoral student at theUniversity of Illinois, Chicago, who's researching fishing cultureand the risks of HIV in Bali. The peddlers' typical patterruns, "Here, take this medicine and go have sex in the brothels.
"In Thailand, most commercial fishermen are Cambodian and Burmesemigrants. They change boats regularly and go to different docks,making it difficult to visit clinics or get test results.At some Thai ports, outreach workers from the nonprofit Raks ThaiFoundation distribute condoms and talk to the men about AIDS. Somefishermen also are being trained to provide HIV education and helptreat STDs.
But experts say there's a need to establish STD clinics at ports andbetter educate the fishermen about everything from safe sex togetting infections at tattoo parlors."We're making progress," says Brahm Press, a program manager for RaksThai. "How much of that progress has been able to reduce the spreadof HIV, we're not certain.
"Edi, 20, is the shortest guy on the dock in Bali, but his muscles are the thickest. He's been on shore nearly two weeks after five straightmonths at sea fishing between Indonesia and Australia.
He brags he had sex with up to 10 women a night. His monthly pay ofabout $70 wouldn't have lasted long at the going rate of about $6 for15 minutes.
He usually doesn't use condoms, complaining it's not satisfying. He'snever been sick or tested for STDs, but points to a friend who's hadsyphilis."There's a medicine for HIV. There is a cure," he says. "Maybe itwill take longer to cure, but you will get better."While at sea, the men get little sleep and regularly risk injury or even death. They could be swept overboard in storms, get fouled inlines or cut off fingers while cleaning fish. They live in crampedboats smelling of diesel and gutted fish. Some question why theyshould lessen the little pleasure they get by wearing a condom.Some fishermen also insert BB-sized, glass or plastic pellets intocuts in their penises for enhancement. The wound is sometimes stillfresh when they make shore, but it doesn't stop them from hitting thebars lined with women in miniskirts."They don't have any self-esteem. They are ordered around by thecompany and the captain to do this and that," said Setiawan, who's researching the fishermen. "Sex workers can give them their self-esteem back.
"Ririn, 22, may sleep with up to 10 men a night. Many are fishermen.Worried she may infect a man who could then give HIV to his wife, shesometimes begs customers to wear condoms - which is more than anyonedid for her.
Most refuse.
"I tell them, 'I'm a working girl. There's a chance you might catchsomething from me,"' she says."The man says, 'That's tomorrow's problem.' "She fears, too, that her daughter Meisa may be infected, but it willtake 18 months for the test results.Now, Ririn's back on the street, still trying to earn enough to opena small shop. She hopes she can quit within a year, but realizes itwon't be easy. Especially with a hungry little one at home and asteady stream of fishermen like Edi, all in search of love for sale.
http://canadianpress.google.com/article/ALeqM5jhV4LiKEuDZPb_IOyuQ-FcoUmo_A
Thursday 12 July 2007
Editorial Review: The Role of Human Leukocyte Antigen E and G in HIV Infection
Piyush Tripathi; Suraksha Agrawal
AIDS. 2007;21(11):1395-1404. ©2007 Lippincott Williams & Wilkins
Posted 07/10/2007
AIDS. 2007;21(11):1395-1404. ©2007 Lippincott Williams & Wilkins
Posted 07/10/2007
Introduction
An important area of HIV research is the immune response and how HIV circumvents it to create a successful and chronic infection. Various studies have provided not only a basic understanding of 'how HIV invades' but also clues for the development of vaccines to fight against AIDS. Although HIV initially evokes an immune response, it later escapes and evades the immune system for a successful infection. Methods of escape from the immune response include rapid mutations altering the organization of cell surface receptors, alterations in the expression profile of human leukocyte antigens (HLA) and destruction of immune effector cells.
HIV infects through exchange of body fluids. The cells mainly infected by HIV are the T helper cells (CD4 T cells), dendritic cells and macrophages. This tropism is generated because HIV utilizes CD4 as a primary receptor plus a coreceptor: CCR5 (expressed on macrophages, dendritic cells and T cells) for the R5 HIV strain and CXCR4 (T cells) for the X4 strain.[1] At the early stages of infection, HIVR5 utilizing CCR5 predominates, whereas at the later stages HIVX4 using CXCR4 is mainly seen.[2,3]
An important area of HIV research is the immune response and how HIV circumvents it to create a successful and chronic infection. Various studies have provided not only a basic understanding of 'how HIV invades' but also clues for the development of vaccines to fight against AIDS. Although HIV initially evokes an immune response, it later escapes and evades the immune system for a successful infection. Methods of escape from the immune response include rapid mutations altering the organization of cell surface receptors, alterations in the expression profile of human leukocyte antigens (HLA) and destruction of immune effector cells.
HIV infects through exchange of body fluids. The cells mainly infected by HIV are the T helper cells (CD4 T cells), dendritic cells and macrophages. This tropism is generated because HIV utilizes CD4 as a primary receptor plus a coreceptor: CCR5 (expressed on macrophages, dendritic cells and T cells) for the R5 HIV strain and CXCR4 (T cells) for the X4 strain.[1] At the early stages of infection, HIVR5 utilizing CCR5 predominates, whereas at the later stages HIVX4 using CXCR4 is mainly seen.[2,3]
In the early stages of infection, the foremost target is CD4 T cells.[4] These cells along with other putative targets harbour mature virus and be carried in the circulation to lymph nodes and lymphoid organs. Here, the virions continue to infect immune cells, preferentially CD4 cells,[5] in some more vigorous way as the density of target cells are higher at these places. This infection as well as the destruction of CD4 cells later on leads to a profound decrease in CD4 cell count. The sudden depletion in CD4 T cells is unlikely to be caused simply by direct viral-induced lysis as the number of cells infected initially may not be sufficient to account for the massive decrease observed.[6] It has been suggested that bystander apoptosis induced by viral antigens or cytokines,[7,8] and downregulation of CD4 receptor by viral HIV-negative effector (Nef) protein,[9,10] may be involved. Other studies have emphasized apoptosis mediated by CD95 (FAS) and CD95L [FAS ligand (FasL)], which, in turn, are stimulated by increased concentration of viral envelope protein gp120 during infection, as a mechanism to account for the preferential depletion of CD4 T cells.[11,12]
With the continuing decrease in CD4 T cells, there is an explosive increase in virus production, which then evokes and is resisted by cellular immune response. After a peak of viral concentration has been reached, a gradual decrease is observed. Though activated cytotoxic T cells (CTL) can partially check infection,[13] which is evident by the appearance by HIV-specific CTL, this counterattack does not eradicate HIV completely as replicating viruses can escape the CTL response by mutation of their activation markers,[14] and through other mechanisms of immune escape. Some studies have suggested that this decline in virus concentration may be because of 'substrate exhaustion', as it is followed by depletion of CD4 T cells,[15,16] which functions as a reservoir for viral dissemination.
Cellular Immune Response to HIV Infection
HIV infection and intrusion of viral particles are counterattacked by CTL-mediated immune responses. Though the cellular immune response fails to control HIV-1 infection completely in most infected individuals, its occurrence is evident in regulating viral load during infection. During acute infection, reduction in viral load coincides with the appearance of HIV-specific CTL,[17,18] and an inverse relationship is established between viral load and HIV-specific CTL.[19] The initial CTL response may be directed against a few epitopes, which subsequently broadens during prolonged antigen stimulation.[20]
CTL could also be expected to have a role during chronic HIV-1 infection as HIV-1-specific T cells remain at high frequency.[21,22] The high concentration of these T cells may result from continued antigenic stimulation. This observation is supported by the fact that there is a steady decline in CTL as viraemia is reduced by HAART.[23] However, in chronic infection without treatment, a high number of HIV-1-specific CTL is seen. Though the CTL response occurs in early as well as in later stages of infection, the epitopes targeted during acute infection often differ from those recognized during chronic infection.[20,24]
When CTL recognize self-HLA molecules loaded with foreign peptide, they activate Fas and secrete perforins and granzymes, which lyse target cells.[25] The CTL produces cytokines (interferon α and tumour necrosis factor α) that affect viral replication.[26] HIV-1-specific CTL also produce the CC chemokines macrophage inflammatory protein 1α and 1β and RANTES, which suppress HIV-1 replication.[27] Even with these various effector functions, CTL cannot completely check viral intrusion in the immune system.
Immune Escape of Cytotoxic T Cells
As CTL do not carry CD4, the main receptor for viral entry and infection, they are anticipated to be a major player in HIV regulation. CTL can use multiple effector mechanisms to regulate viral replication,[25,28] including lytic mechanisms and CC chemokine-mediated blockade of viral entry.[29,30] The existence of HIV-specific CTL and their successful involvement in protection against disease transmission confirms their importance in disease regulation.[31,32]
As CTL can pose a strong regulatory force against HIV, virions that can escape the CTL response have a selection advantage. HIV has a high mutational rate (1 in 105 bases,[33]) and so can produce many mutants, but only those mutants that do not cost in terms of viral fitness would be selected. These mutational escapes lead to failure of vaccines as well as of immune regulation, as escape variants do not generate specific CTL but keep on eliciting the proliferation of CTL specific for wild type.[34] Escape mutations can work through many mechanisms, including alteration of epitopes presented on HLA for T cell receptors, lack of antigen processing, absence of improper interaction with HLA and finally lack of recognition by T cell receptors. During HIV infection, selective pressure imposed by CTL leads to the generation of various escape mutations and these variants may constitute the majority of the total viral pool. It has been shown that the ratio of non-synonymous substitutions to synonymous substitutions was higher in the CTL epitope. This further confirms the role of CTL selection pressure for occurrence and then for maintenance of these mutations.[35] Later on, evidence of escape mutations in HLA-B8-restricted epitope in Nef, HLA-B44-restricted epitope in Env and HLA-B27-restricted Gag epitope KK10 have supported the CTL-mediated selection of these mutations.[36]
Nef-Mediated Downregulation of Major Histocompatibility Complex Class I
In addition to escape mutations, HIV has strategies that can make the infected cell undetectable by the immune system. The detection of any cell depends on cell surface markers and so effective strategies alter the organization and expression of such markers. To escape from CTL response, HIV inhibits surface expression of the host major histocompatibility complex (MHC) class I, which is most important for CTL recognition; this is achieved through a viral protein called Nef. HIV-1 Nef is a 27-34 kDa multifunctional protein that has no apparent enzymatic activity but functions as an adaptor protein that enters the cell membrane through amino-terminal myristoylation. Though the exact mechanism by which Nef disrupts MHC class I cell surface expression is not clear, the viral protein binds to the cytoplasmic tail of the class I protein and may disrupt class I trafficking.[37] The cytoplasmic domain of class I antigens has a highly conserved region of 33 amino acid residues with nine conserved serine residues; Nef protein interacts with this via amino-terminal α-helix, polyproline and acidic domains.[38]
It was initially thought that Nef reduced MHC class I cell surface expression by accelerating endocytosis and promoting retrograde transport of internalized class I molecules to the trans-Golgi network (TGN).[39] Nef protein can interact with phosphofurin acidic cluster sorting protein 1 and then can activate phosphatidylinositol 3-kinase,[40] guanine exchange factor ARNO and finally ADP ribosylation factor 6.[41] This pathway leads to internalization of MHC class I molecules to 'ADP ribosylation factor compartments' that finally reach the TGN. However, more recent work has shown that Nef disrupts transport of MHC class I in the secretory pathway to the cell surface, rather than causing endocytosis from the cell surface. Further, it has been demonstrated that adaptor protein 1 (AP-1) is necessary for Nef to disrupt class I trafficking.[42] The main function of AP-1 is to sort proteins at the TGN by binding their cytoplasmic tails to clathrin and directing them to endolysosomal pathways.[43] Nef-mediated disruption of class I surface expression may occur by allowing interaction between the cytoplasmic tail of an MHC class I molecule and AP-1, thus redirecting the molecules from the TGN to the lysosomes for degradation,[42] as shown in Fig. 1. Recent work by Kasper et al.,[44] has shown that Nef targets MHC class I in T cells early in the biosynthetic pathway by preferentially binding newly synthesized hypophosphorylated class I molecules. The preferential interaction of Nef prevents phosphorylation of these molecules and so also prevents them reaching the cell surface In summary, the work of Collins and coworkers,[42,44] has demonstrated that Nef preferentially binds hypophosphorylated class I molecules, thus preventing completion of the secretory pathway that would finally provide an antigen-presenting receptor on the cell surface to activate killing of the virus-infected cell. Transport of class I molecules from the cell surface to the TGN occurs normally in infected cells but the class I molecules are then diverted to lysosomes through Nef-assisted binding of AP-1 to their cytoplasmic tail; this further inhibits their phosphorylation as well as their surface expression.
Figure 1.
Probable mechanism of viral HIV-negative effector (Nef)-mediated major histocompatibility complex class I internalization that may fail with human leukocyte antigen (HLA) G. Nef and adaptor protein (AP) 1 interact with the cytoplasmic domain of the class I in the trans-Golgi network (TGN) and then redirect class I protein-containing vesicles to the endolysosomal pathway. The truncated cytoplasmic domain of HLA-G makes Nef-mediated recycling ineffective as Nef proteins cannot dock on HLA-G and so surface expression of HLA-G does not change during HIV infection.
HLA Genotype and Cytotoxic T Cells
The HLA antigens activate cellular responses by forming the antigen-presenting component on the cell surface that interacts with CTL, directs them against the infected cells and activates natural killer (NK) cells of the innate immune response by interacting with the killer cell immunoglobulin-like receptor (KIR) family of surface molecules. There is substantial evidence that immune responses are effective in challenging the infection and transmission of HIV disease.
Though various genetic factors have been associated with susceptibility to HIV ( Table 1 ), investigations of the role of HLA antigens has concentrated on three areas: zygosity of HLA loci, sharing of alleles, and specific HLA allelic/haplotypic association with the outcome of disease. It has been shown that homozygosity at the class I loci is associated with relatively rapid progression to disease compared with heterozygotes.[54] This heterozygote advantage probably stems from the ability of such individuals to present a wider array of virus-derived epitopes to a more diverse CTL repertoire. This heterozygous repertoire will not only enable recognition and destruction of a greater breadth of infectious agents but will also require many more escape mutations for effective avoidance of the CTL response. Hence, heterozygosity may be associated with delayed progression to AIDS.[50] However, it is also conceivable that virus may become adapted and resistant to highly frequent alleles more easily in that population, and so a rare allele may have selective advantage in HIV disease progression.[55] The rare allele selective advantage may work in conjunction with heterozygote advantage, as the protective rare alleles are more likely to be present as heterozygotes.
Another genetic component that predisposes to the progression of AIDS is HLA sharing. Where the MHC class I is common to the donor and recipient, the basis of successful transplantation, it would lead to increased susceptibility to viral infection. One natural model of viral transmission between HLA-sharing donor and recipient is mother-to-child transmission, which further supports increased transmission of HIV in these circumstances.[56] Further, significant increase in susceptibility to HIV has been shown to be associated with concordance at the HLA-B locus but not at HLA-A or HLA-C.[57]
Knowing that a certain viral escape mechanism is likely to develop under a particular genetic selection pressure, it can be anticipated that an escape variant well adapted to a particular genetic profile and then transmitted to a host of similar genetic set up would be able to escape immunological challenges in the new host also. This may be a mechanism for susceptibility to viral transmission in hosts with HLA alleles in common. By comparison, MHC class I disparity may induce anti-HLA antibodies on passage of the virus and so may prevent HIV infection at early stages. Such a defence would be lacking in HLA concordant individuals, increasing successful transmission of HIV virus.
Previous research in genetic predisposition to viral susceptibility in the context of HLA has concentrated on specific alleles. Various studies have confirmed the contribution of specific class I alleles and more particularly HLA-B alleles in the outcome of disease.[58] This remarkable contribution of HLA-B may be because this group has the highest diversity among the class I antigens: approximately 661 alleles compared with 372 in HLA-A and 190 alleles in HLA-C.[59] Further, substantially greater selection pressure would be imposed on HIV by HLA-B compared with other class I antigens. Consistent association with delayed disease progression has been seen with HLA-B*27 and HLA-B*57.[51] Though the HIV HLA-B*57-specific epitope 'TW 10' may undergo an escape mutation, T242N, under selective pressure, this may cost in terms of viral fitness as the virus reverts after transmission to a new host.[60] Another allele, HLA-B*35, has been implicated as the class I susceptibility allele for AIDS.[52] HLA-B*35 heterozygotes have a rapid progression to AIDS, and homozygotes progress twice as fast as HLA-B*35-negative individuals. The most deleterious effects of HLA-B*35 are seen with its two subtypes, HLA-B*3502 and B*3503, which have proline at anchor position 2 of their loaded peptide and non-tyrosine residue at position 9.[52] By comparison, HLA-B*3501 containing tyrosine at position 9 does not have any substantial effect on disease prognosis. While both HLA-B*35 subtypes can equally induce a CTL response, viral load was cleared less effectively by non-tyrosine-containing HLA-B*3502 and B*3503 compared with HLA-B*3501.[61] It may, therefore, be possible that altered epitope recognition by HLA-B*3502 and B*3503 will induce CTL that may not specifically function against HIV-1-infected cells.
Some HLA-B alleles have been shown to influence the outcome of disease progression by interacting with KIR on NK cells. The Bw4 motif (residues 79-84 of the α3 domain) of various HLA-Bw4 alleles may interact with activating receptors KIR3DS1 of NK cells, thus facilitating clearance of HIV-1-infected lymphocytes and slowing disease progression.[62]
Studies have also been performed to examine particular MHC class II genes, but no consistent effects have been revealed. One recent study implicated the DRβ1*13-DQβ1*06 haplotype in viral suppression during treatment.[63]
Role of HLA-G and HLA-E in Progression of HIV Disease
Among the myriad of mechanisms adopted by HIV to avoid the human immune response is interference with the expression of HLA antigens. One evasion strategy is to downregulate cell surface class I classical antigens (HLA-A and HLA-B) to avoid HIV-specific CTL responses. Normally any change in the self HLA profile of cells is easily detected by immune surveillance and such cells are then subjected to degradation. However, despite reduced expression of class I antigens, HIV-infected cells are resistant to lysis by NK cells. During viraemic HIV-1 infection, there is expansion of an anergic subset of NK cells that do not respond to stimulation with MHC-devoid target cells. These NK cells have increased expression of SHIP (SH2-containing inositol phosphatase), which may be responsible for the reduced functional activity of these cells in chronic HIV-1 infection.[64] Various NK cell receptors that recognize MHC-independent ligands can regulate key cytolytic NK functions. A recent study has demonstrated that these inhibitory receptors recognizing an MHC-independent ligand are overexpressed in SHIP knockout mice and, therefore, may regulate NK cell cytolytic activity. This would suggest that SHIP plays an important role in regulation of this MHC-independent inhibitory NK receptor repertoire, which, in turn, is crucial for NK recognition and cytolysis of various targets.[65] However, this immunoprotection could also be achieved by increased expression of HLA-G and HLA-E during HIV infection. These antigens are less polymorphic than their classical counterparts. Where HIV Nef downregulates surface class I antigens by interacting with their cytoplasmic domain,[66] it may not be able to interact with non-classical HLA-I antigens such as HLA-G, which has a truncated domain,[67] (Fig. 1). Apart from any effects of the shorter cytoplasmic tail in HLA-G, it has been speculated that various mechanisms may upregulate HLA-G and HLA-E. The impact of these non-classical class I antigens on susceptibility to HIV infection is supported by their immunoregulating properties (Fig. 2).
Figure 2.
Upregulation of non-classical major histocompatibility complex class I human leukocyte antigen (HLA) antigens G and E by HIV as a strategy of immunodownregulation. HIV-negative effector (Nef) involved in class I downregulation does not affect HLA-G expression. HIV, through increased interleukin 10 (IL-10) during infection, can upregulate HLA-G expression, and viral peptide p24 amino acids 14-22 can upregulate HLA-E expression. Enhanced HLA-G and HLA-E can regulate natural killer (NK) cells by interacting with their inhibitory receptors. HLA-G can also control T cell response to HIV by directing T cells to apoptosis. KIR, killer cell immunoglobulin-like receptor; NKG2A, an NK-activating receptor.
HIV and HLA-G With a Truncated Cytoplasmic Domain
HLA G was cloned by Geraghty et al. in 1987.[67] It is less polymorphic, as only 15 alleles are known to date. It has restricted tissue distribution compared with the classical class I antigens. Though initially HLA-G was implicated in the maintenance of tolerance during pregnancy, its role has been explored in the tumour escape mechanism in various cancers and also in organ transplantation.
The exon organization of HLA-G is similar to the classical class I molecules, with three external domains (α1, α2, α3), a transmembrane domain and a cytoplasmic domain, and it is associated with β2-microglobulin to make the complete structure.[68] But HLA-G is more peculiar as it possesses a premature stop codon in exon 6 that results in a truncated cytoplasmic tail (it translates 6 amino acids instead of 30).[67] HLA-G exists in multiple isoforms, created by alternative splicing.[69] Seven different HLA-G transcriptional isoforms have been described; four of these encode membrane-bound forms whereas the remaining three encode soluble isoforms. HLA-G is identified as an immunoregulatory molecule as it can interact with inhibitory KIR of NK cells. So far, three HLA-G specific KIR have been identified: ILT-2 (LIR-1), ILT-4 (LIR-2) and KIR2DL4 ( Table 2 ).[74,75] In addition to acting via the innate mechanisms, HLA-G also provides protection through acquired immunity. HLA-G5 induces apoptosis of activated CD8 cells through activation of the Fas/FasL pathway,[76] whereas HLA-G1 suppresses CD4 lymphocyte proliferation.[77] Interaction of HLA-G1 with KIR of T cells can inhibit the antigen-specific HLA-restricted CTL response,[76] thus confirming the functionality of HLA-G in protecting cells from all possible immune responses.
HIV infection is characterized by loss of HLA-A and HLA-B, but the expression of HLA-G remains unaffected or at least not decreased. Along with inability of viral Nef to downregulate HLA-G, there could be some changes indirectly influencing the expression of HLA-G, particularly increased interleukin 10.[78] It has been shown that this cytokine upregulates expression of HLA-G.[79] Lozano et al.,[80] demonstrated the increased expression of HLA-G in all monocytes and some T lymphocytes after HIV infection. Other evidence had implicated HAART in upregulation of HLA-G,[81] but the study by Lozano et al.,[80] excluded this mechanism by showing elevated levels of HLA-G in untreated HIV-positive individuals. A contradictory report by Derrien et al.,[82] showed downregulation of HLA-G in HIV infection. Though these authors agreed that this was an Nef-independent process, as HLA-G is unable to interact with Nef, they thought it was more likely to be a viral protein U (Vpu)-dependent mechanism as HLA-G possesses a dilysine motif (RKKSSD) at -4 and -5 from the carboxy-terminus,[67] with which Vpu could interact and interfere with further intracellular trafficking of HLA-G. The difference between these two studies may arise for two reasons. First, Derrien et al.,[82] studied expression in cell lines, which would have subtle differences in microenvironment from in vivo. Second, the stage of infection may have a profound effect on the microenvironment, which, in turn, could alter HLA-G expression. Derrien et al.,[82] studied HLA-G expression in acute HIV infection, and their results are similar to other acute viral infections such as human cytomegalovirus and herpes simplex virus. These both decrease cell surface expression of HLA-G1, but the former particularly can increase HLA-G1 expression upon reactivation.[83,84] Possibly the expression of HLA-G could be enhanced in the natural course of HIV infection so that the situation in chronic infection would be as shown by Lozano et al..[80]
Further, HLA-G polymorphism is also associated with the risk of HIV infection. Matte et al.,[85] carried out an extensive study of HLA-G polymorphism in 456 HIV-seropositive and 406 HIV-seronegative African women and found significant association of G*0105N with protection from HIV-1 infection and G*010108 with susceptibility to infection. Allele G*0105N is characterized by deletion of cytosine at position 130 of exon 3, leading to frameshift and introduction of a stop codon in exon 4.[86] Hence allele G*0105N impedes production of a functional HLA-G molecule. The most likely reason for association of G*0105N with protection from HIV infection would be that this impairs the function of HLA-G and so downregulation by HIV would be absent or decreased. Recently Lajoie et al.,[53] presented more extended and explicit data for HLA-G polymorphism in the same cohort. They found that women carrying G*0105N had a 2.2-fold decreased risk of HIV-1 infection compared with women without G*0105N. They also reported an HIV- seronegative woman who was homozygous for G*0105N.
The G*010108 allele, reported to be associated with increased risk of HIV-1 infection,[85] has a synonymous substitution (proline) of G to A at codon 57. Though this mutation does not bring about any change in amino acid sequence, it is in the vicinity of Glu-63, which interacts with the P2 position of loaded peptide.[87] In the mouse homologue Qa-2, P1 arginine of the peptide interacts with Glu-62, Glu-63, Tyr-59 and Trp-167 residues, three out of four of which are in close proximity to Pro-57. Another HLA-G allele, G*010401, shares variation at codon 57 with G*010108, although it also has a non-synonymous substitution at codon 110. The G*010108/G*010401 genotype has been shown to have a greater association with increased risk of HIV infection.[85] However, this may be because G*010401 is a high secretor allele associated with increased secretion of soluble HLA-G molecules, consequently being open to more systemic downregulation. All individuals identified with G*010108/G*010401 were homozygous at codon 57.[85] Though this position is not directly involved in the presentation of peptide, zygosity of HLA at this position could still affect susceptibility to HIV infection. Aikhionbare et al.,[88] have shown that discordance at codon 57 of HLA-G exon 2 was significantly associated with non-transmission of HIV-1 infection in mother-child pairs studied to investigate the risk of perinatal HIV transmission. This is probably in agreement with the observations discussed above that HLA sharing leads to increased susceptibility to HIV-1 transmission. However, more studies are needed to validate these observations, particularly for HLA-G.
HIV and the Less Polymorphic HLA-E
HLA-E was initially recognized as HLA-6.2 and was mapped to chromosome 6p21.3 between HLA-C and HLA-A.[89] HLA-E has a wide tissue distribution including T cells, B cells, activated T lymphocytes and various other cells such as placenta cells and trophoblasts.[90,91] HLA-E is less polymorphic, having only three alleles identified so far. These three alleles can be differentiated as HLA-ER (0101) and HLA-EG (01031 and 01032) by a non-synonymous substitution of arginine by glycine at position 107. Alleles 01031 and 01032 differ only by a synonymous mutation at codon 77.
HLA-E also has NK-regulating properties, as HLA-E has been identified as a ligand of a subset of the immunoglobulin superfamily of NK cell receptors, and their interaction with KIR of NK cells may be responsible for inhibition of killer activities in these cells.[92] HLA-E is distinct in that it depends for surface expression on a highly conserved nonamer peptide derived from the signal sequence of other class I molecules including HLA-A, HLA-B, HLA-C and HLA-G, but not HLA-F.[93] The peptide structure is very important, as only appropriate peptide can be loaded onto HLA-E, enabling expression and subsequent protection of target cells by interaction of the HLA-E-peptide complex with the CD94/NKG2 receptor of NK cells.[94]
A potential role for HLA-E in susceptibility to HIV has been neglected until a recent report showed that it was upregulation during p24-positive HIV-1 infection.[95] Though HLA-E has wide tissue distribution, its dependency on peptides derived from MHC class I may affect its expression on HIV-1-infected cells, as they have decreased class I expression. However, HLA-E expression could be supported by peptides derived from HLA-G or of viral origin. There is evidence of HLA-E upregulation by viral peptides: UL40-derived peptide in human cytomegalovirus,[96] and core 35-45 peptide in herpes simplex virus.[97] It has also been shown that HLA-E is upregulated by peptide 14-22 derived from HIV p24. Comparison of the HIV p2414-22 peptide with the sequences of other known HLA-E-specific peptides showed that it was very similar, with only subtle changes, and matched the HLA-E-binding criteria. HIV p2414-22 shares isolucine at position 2, which appears to be essential for HLA-E interactions, and has residues at positions 4, 6 and 7 that are similar to those identified in other HLA-E-specific peptides. HIV p2414-22 peptide has asparagine at position 5, which may be essential for HLA-E-peptide complex interaction with CD94/NKG2A, an HLA-E-specific inhibitory NK cell receptor. It has been reported that upregulation of HLA-E by HIV p2414-22 can inhibit cytolytic function of NK cells by interacting particularly with inhibitory CD94/NKG2A receptor.
Specificity of this HLA-E-peptide complex interaction with CD94/NKG2A, responsible for inhibition of NK cell cytolysis, was further confirmed by studies that restored NK cell cytolytic activity by blocking HLA-E with specific monoclonal antibody 3D12 or blocking CD94/NKG2A with specific anti-NKG2A antibody.[98] The HLA-E-specific HIV p2414-22 peptide is derived from HIV Gag, and as it consists of a putative proteasome cleavage site, it is conceivable that the peptide could be processed by proteasomal cleavage during natural HIV infection.
There are reports relating to HLA-E polymorphism with susceptibility to HIV-1 infection. Lajoie et al.,[53] have demonstrated association of HLA-EG allele with protection against HIV infection. HLA-EG is known to have better immunoregulating properties than HLA-ER. HLA-EG has also been associated with other pathologies, for example nasopharyngeal carcinoma,[98] and affected pregnancy outcome.[99] Strong et al.,[94] have shown that HLA-EG-peptide complex always has higher surface expression than the HLA-ER-peptide complex and HLA-EG is also more thermally stable. When affinity with peptides of various origins was tested, it was found that the relative affinity of HLA-EG for peptide was significantly higher than that of HLA-ER.[94]
As there is substantial evidence for a role for HLA-EG in efficient immunoregulation, its association with better prognosis in HIV infection would be expected; yet the converse is observed, which further suggests that, under cellular stress, HLA-E upregulation instead of immunoprotection supports immunosurveillance. HLA-E can interact with the leader peptide derived from heat shock protein 60 (hsp60),[100] which is generated in response to cellular stress. However, presentation of hsp60-derived peptide on HLA-E would not be sufficient to inhibit NK cell cytolytic activity, as the HLA-E-peptide complex could not interact efficiently with CD94/NKG2A.[100] The same situation might also occur with the HIV-derived peptide. As KIR receptors specifically identify HLA-E complexed with cellular peptide in order to stimulate NK cell inhibition, complexes with non-cellular peptides might interfere with this recognition by the inhibitory receptor. Further HLA-EG has higher stability and affinity with peptide than HLA-ER [94] hence it may have a more rigid three-dimensional conformation - and even subtle changes could be identified by CD94/NKG2A. There is also the possibility that HLA-E could induce virus-specific CTL immune responses, as in the case of cytomegalovirus-derived peptide. However, these assumptions require extensive functional studies to validate the impact of HLA-E and HIV-derived peptide on NK cell receptors.
Table 1. Various Genetic Factors in HIV Susceptibility
Table 2. Interaction of Human Leukocyte Antigen G and E With Different Natural Killer Cell Receptors
References
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Reprint Address
Professor Suraksha Agrawal, Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow (UP) 226014, India. E-mail: suraksha@sgpgi.ac.in
Piyush Tripathi, Suraksha AgrawalFrom the Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow (UP) 226014, India.
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