14 MAY 2010, VOLUME 11, ISSUE 16

Nigeria, together with over 120 countries in 2006 made an historic commitment to scale-up the national response towards achieving universal access to HIV prevention, treatment, care and support. But while HIV prevalence and new infections are declining, cries of stigma and donor fatigue are threatening hard earned development gains, writes Ben Ukwuoma.

The cries of discrimination and stigmatization of People Living with HIV/AIDS that rented the air at the African Hall of the International Conference Centre, Abuja was a pointer of what would likely dominate discussions at the fifth National Conference on HIV/AIDS, which ended last Thursday.

Expectedly, on the lips of the 4,000 researchers, clinicians and stakeholders, that attended the four-day talkshop was the urgent need to pass into law the anti-discrimination and stigma bill before the National Assembly. To them the passage of the bill would bring justice and succor to People Living with Human Immunodeficiency Virus (PLHIV) who have been delayed and denied justice.

The Coordinator of Network of People Living With HIV/AIDS (NEPWHAN), Mr. Edward Ogenyi, captured the feelings of his members thus: "Many are loosing their jobs, women are ejected out of their matrimonial homes and there is no law against such practices". A gory picture of healthcare services in the country was also painted by the participants.

HIV vaccine research is diverging from classic vaccinology and its focus on the adaptive immune response, to a field of its own. There has been a shift from protecting against infection to changing the nature of the infection, Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases (NIAID), in Bethesda, Maryland, said in his keynote address here at the National Foundation for Infectious Diseases 13th Annual Conference on Vaccine Research.

The principles of classic vaccinology are that "the response to natural infection is the guidepost to the vaccine. . . . The proof of concept is already done for us by the natural response to infection. . . . The vast portion of people spontaneously recover," he said. "The virus is cleared and eradicated and the person is left with a protective immunity that, in most cases, is complete and lifelong."

But beginning with the gp160 trial in 1987, researchers quickly learned that the principles of classic vaccinology "didn't apply particularly well to HIV. . . . I've been taking care of HIV-infected individuals for almost 29 years and I have never seen anybody eradicate the virus or spontaneously recover," Dr. Fauci said. "And protective immunity against subsequent infection doesn't appear to occur. That is amazing. You are infected with a microbe and, while you are infected, you get reexposed to the microbe and you get reinfected. That is depressing for vaccinologists."

"There is no proof of concept to help us. We really have to start from scratch," he said. Basic research has been able to generate a few antibodies that are broadly neutralizing to laboratory strains of HIV, but not to wild-type virus, Dr. Fauci noted.

Once these facts began to sink in, the field shifted toward developing a vaccine that would not protect against infection but that might shift the course of disease progression to one that is less lethal, perhaps even benign. The public health goal of reducing transmission might be accomplished by lowering the viral load of those who are infected. "Those attempts, thus far, have not been successful," Dr. Fauci said.

STEP Back
The early stopping of the STEP trial, which was testing an HIV vaccine developed by Merck with the support of NIAID, led the field to another reevaluation. The mix of basic and developmentally oriented research was recalibrated back toward the former. 

Then came the Thai study (RV144) "using a pox virus vector and an envelope boost, which, when you looked immunologically, had virtually none of the classical parameters that would predict protection. [Cytotoxic T lymphocytes] were nowhere to be found; neutralizing antibody, nowhere to be found," Dr. Fauci said. But "for the first time we found a modest, weak, but real signal of prevention of acquisition," he said. "There was no doubt that the Kaplan-Meier curves were separated. We now had a weak signal upon which to build."

The fact that the vaccine had no effect on the viral load of those who became infected confounded the expectations of many, but not Dr. Fauci. "I think it argues for the dichotomy of effect on acquisition vs the control of chronic viral infection. It is telling us something that perhaps we should have realized a long time ago - an immune response that protects against acquisition might be quite different from the immune response that actually controls chronic virus replication."

"What we have now is a whole new way of looking at things. . . . We really know what is going on and what is needed."

The United Nations agency focusing on HIV/AIDS has welcomed a decision by the global fund which manages resources to combat the disease to start receiving proposals for grants this month, saying the decision will enable countries to maintain the momentum of efforts to stem the spread of the pandemic.

"AIDS is not over in any part of the world," Michel Sidibe, Executive Director of the Joint UN Programme on HIV/AIDS (UNAIDS), said in a statement yesterday. "It is imperative that we keep resources flowing to people and communities struggling daily with the impact of HIV," Mr. Sidibe said of the decision by the board of the Global Fund to Fight AIDS, Tuberculosis and Malaria to begin receiving applications for grants to fund campaigns against the diseases.

UNAIDS also expressed its appreciation of the Global Fund's decision to continue financing proposals addressing the needs of most-at-risk populations. Sex workers, injecting drug users, men who have sex with men and other key marginalized populations are often ignored by funding mechanisms, according to UNAIDS. Setting aside resources for the most vulnerable people will ensure that communities can rapidly scale-up their AIDS response and meet the goal of zero new HIV infections, the agency added. The Global Fund's decision will also allow upper-middle-income and lower-middle-income countries, which often have concentrated epidemics among populations at higher risk, to access these resources.

Clinical research in South Africa is in serious decline because of two decades of "disinvestment" - leading to an ageing workforce, "chronic underfunding" of its Medical Research Council and "grossly insufficient" funding for research professorships, says a report. Lack of government funding is driving South African researchers into working on diseases of the affluent, for the pharmaceutical industry, or the HIV and TB agendas of external donors, says the Academy of Science of South Africa.

Over half of the country's expenditure on clinical research comes from the private sector, according to the report published last month (22 April). The last two decades have seen a "largely unplanned, but cumulative, disinvestment in publicly funded programmes resulting from the withdrawal of the health departments of provincial governments from this sector, the absence of discounts for research tests from the business model for the National Health Laboratory Service, chronic underfunding of the Medical Research Council ... and the lack of funding streams to universities that might in principle have been applied to meet the overall shortfall in support.

"There is little likelihood that continuation of the present situation is compatible with rebuilding and sustaining solid research capacity in the clinical domain," adds the report, by the Academy's panel of health scientists and scholars.

A tenth of South Africa's state expenditure goes on public health services, which the report applauds, but adds that the proportion going to research is "much too little" - 0.15 per cent of gross domestic product (GDP). The report calls for, amongst other things, a national funding scheme for clinical research, with two per cent of GDP committed to research and development (R&D), of which 20 per cent should be allocated to health research.

The Tanzanian government has deported several AIDS activists and cancelled a demonstration to protest decreasing funding for HIV at the World Economic Forum (WEF) in the commercial capital, Dar es Salaam. 

"We met with [South African singer and AIDS activist] Yvonne Chaka Chaka and gave her our memorandum to present to the leaders attending the WEF; shortly thereafter we were arrested," Bactrin Killingo of the International Treatment Preparedness Coalition (ITPC), told IRIN/PlusNews. "We spent four or five hours at the police station making statements, after which we were escorted to our hotels to collect our belongings and then to the airport, where we were deported." None of the activists, who were from a variety of African countries, were charged. 

A planned national workers' union strike prompted Tanzanian President Jakaya Kiwete to cancel all demonstrations this week. "We had received permission to hold the demonstration [on 5 May], but later received a letter cancelling it ... Only ten of us delivered the memorandum - it was not a demonstration," Killingo said. 

The US international AIDS effort known as PEPFAR (the president's emergency plan for AIDS relief) has pledged an additional $30m for programmes aimed at reducing gender based violence in three partner nations: Tanzania, Mozambique, and the Democratic Republic of the Congo. The announcement came on 5 May at a consultation meeting in Washington, DC, for those working in the field.

The empowerment of women and girls has become a policy cornerstone of the family of United Nations agencies and is strongly supported by the US secretary of state, Hillary Clinton, said PEPFAR's administrator, Eric Goosby.

"Our hope is that this initiative will move us closer to our goal of sustainable gender based violence responses," Dr Goosby said. The funding will be used to take lessons from pilot programmes and roll them out into coordinated and integrated national responses that are tailored to the needs of individual countries and communities.

One of China's most prominent HIV/Aids activists has fled to the US with his family owing to increasing pressure from the Chinese authorities. Wan Yanhai's departure comes less than a year after another Aids campaigner moved to America, and amid warnings that officials are clamping down on the China's fledgling civil society.

"As an organisation and personally, the attacks from the government had become very serious. I had concerns about my personal safety and was under a lot of stress," Wan told the Associated Press. "When I am in China, the authorities look at me like I am a bird in a cage. They say: 'If you don't listen to me, then I will eat you.' But after I leave the country, they will see me in a new light, because I am no longer in their cage."

Wan, founder of Beijing's Aizhixing Institute, said he expects to stay in the US for two to three years. He founded Aizhixing in 1994 to raise awareness and fight discrimination. But while he praised the government for strides it made on the issue in recent years - such as increasing funding and attempting to address the stigma of having the virus in China - the authorities were less tolerant of his work on sensitive issues, such as highlighting the cases of those who contracted HIV from blood transfusions.

Wan had been detained and questioned several times, but said he felt increasing pressure in recent months - following checks by tax, education and propaganda officials, and the state administration for industry and commerce. Police recently interrupted a lecture he gave at a university. Tightened regulations on foreign donations to Chinese NGOs have also caused funding problems, he said.

Despite decades of effort, no magic bullet for AIDS has been invented. The obstacles are huge. The virus mutates as fast in a day as a flu virus does in a year, but can also lie dormant indefinitely. Since no one has ever been cured, there is no natural defense to mimic. And, since it attacks the CD4 cells that are the "fire alarms" of the immune system, vaccines that stimulate immunity may just give it more targets.

Even in wealthy countries, it can only be controlled; antiretroviral cocktails keep it from replicating. Patients are not cured, but may survive into old age. With just four million people on treatment worldwide and donors balking at the idea of supporting 33 million or more, a miracle is needed. But none is on the horizon.

The latest failed vaccine trial, in Thailand, took six years. It may have temporarily protected a few participants, but even that required six shots spaced months apart. That is too complicated for places like rural Africa, where polio drives often fail, though they involve only a few pink drops in babies' mouths. Dr. Anthony S. Fauci, who oversaw the Thai trial, said he saw "no chance" of a vaccine in the next few years and a "reasonable" chance of one in 20 years.

The quest for a vaginal microbicide is also stalled. Women need a product that is not messy and can be inserted secretly, because many men react furiously to any suggestion that they are infected. Also, because many women want children, it must block a tiny virus without blocking sperm, which has been likened to stopping a million BBs streaming down a road while a fleet of Mack trucks breezes through.

Trials using sticky chemicals have proved futile. An early trial of a spermicide actually increased infections. In July, results are due from a trial of a gel containing the antiretroviral drug tenofovir, which worked well in monkeys. It is expected to show neither a major breakthrough nor an utter failure, since, ethically, scientists would have had to stop the trial prematurely if preliminary results showed either trend.

Sharon Hillier, principal investigator for the Microbicide Trials Network, said she was still "hopeful" that such a gel, or a vaginal implant that released drugs slowly, would be ready some day. "But," Dr. Hillier said, "it's going to be a long and difficult passage."

This article is part of a four-part series on HIV/AIDS published in the online edition of the New York Times on 9 May 2010. Articles also in this series:
At Front Lines, AIDS War Is Falling Apart
As the Need Grows, the Money for AIDS Runs Far Short
Cultural Attitudes and Rumors Are Lasting Obstacles to Safe Sex

US researchers say they are a step closer to understanding why some people have natural protection against HIV. They believe rare individuals who progress very slowly to Aids when infected make white blood cells that are better at fighting the virus. The findings, published in Nature, may help international efforts to design an effective Aids vaccine. But the research team at MIT and Harvard says any such vaccine is at least a decade away.

The findings relate to so-called "elite controllers" - a small number of people who, when exposed to HIV, progress very slowly to Aids or never develop it at all. In the late 1990s it was discovered that these individuals - about one in 200 of those infected with HIV - carry a specific gene, known as HLA B57. The research team, led by MIT Professor Arup Chakraborty and Harvard Professor Bruce Walker, found this gene causes the body to make more potent killer T cells - a type of white blood cell that fights infections. This helps them to keep the HIV virus at bay, but also makes them more susceptible to autoimmune diseases, where the body's immune system turns on itself. The work is based on computer modelling of how immune cells develop in a specialised organ of the immune system known as the thymus.

Vaccine puzzle
The researchers say the study has implications for designing an effective vaccine. It could help them develop vaccines that provoke the same response to HIV that individuals with "natural immunity" can do on their own. But they say even if they knew exactly what vaccine they wanted to make, it would take at least a decade to reach the hands of a healthcare worker.

Prof Bruce Walker told the BBC: "Some people are able to control HIV on their own and it's really critical for us to understand how this happens. This study takes us a step forward in understanding that." Prof Chakraborty added: "It shows another piece in the puzzle of what we want a vaccine to do."

An alarming 56,300 new infections of HIV/AIDS are reported each year in the United States alone. And 1.1 million people are living with HIV, of whom 20% do not know they are infected. The global count of new annual infections stands at 2.7 million, as per the facts revealed last week during a briefing that focused on combating the deadly virus. According to Anthony Fauci, MD, Director, National Institute of Allergy and Infectious Diseases, National Institutes of Health, the common goal in HIV/AIDS research is to control and ultimately end the pandemic.

Held in collaboration with Representatives Rosa DeLauro, Barbara Lee, and Elliot Engel, the briefing was cosponsored by amfAR, the Foundation for AIDS Research; AVAC; HIV Medicine Association; IDSA/HIVMA Center for Global Health Policy; the San Francisco AIDS Foundation; and the Treatment Action Group.

Dubbing the advances by the virus as stunning, the briefing highlighted the need to do away with the impression that HIV/AIDS had been combated. "There is an impression that we really have our arms around this and that things are stable - but they are not," Dr. Fauci said. "Currently, worldwide, there are 2.7 million new infections each year, which is still really completely and totally unacceptable," he said.

Dr. Fauci asserted that the three vital, common goals that needed to be achieved for restraining the HIV/AIDS pandemic from spreading further included scaling up delivery of proven therapies, curing existing infections and preventing new infections.

South Africa's renewed commitment to combat AIDS has drawn praise, but in the worst-hit province in the worst-hit country in the world, life - and death - hasn't changed much because of stigma and a lack of resources.

After years of official denial and delay, South Africa's government last year embarked on an anti-AIDS drive that will stretch its human and cash resources, perhaps to breaking. The first step began in April, when South African President Jacob Zuma launched a counseling and testing campaign, aiming to test 15 million people and distribute 2.5 million condoms.

This week at an AIDS clinic in Ndulinde, about 55 miles (90 kilometers) north of the main KwaZulu-Natal province town of Durban, nurses said despite what the government says is one of the largest initiatives to fight the spread of AIDS, nothing has changed because they don't have the time or the personnel.

Ndulinde clinic's five staff members - only two registered nurses, none are doctors - say they already are struggling to cope with the up to 300 patients daily.

South Africa, a country of some 50 million, has an estimated 5.7 million people infected with HIV, more than in any other country. KwaZulu-Natal is South Africa's most populous province located on the east coast along the Indian ocean. Here, according to South African officials, 38.7 percent of pregnant women tested at clinics are HIV positive, well above the national average.

The Bill & Melinda Gates Foundation announced backing for 78 science projects on Tuesday, including a vaccine triggered by human sweat and a laser vaccine.

The $34 billion Bill & Melinda Gates fund invests in scientific projects that are aimed at improving global health. Each of the 78 projects will receive a $100,000 grant for further study from the foundation. The foundation's Grand Challenges Explorations scheme awarded the grants as part of its five year, $100 million initiative to promote innovation in global health.

"We are convinced that some of these ideas will lead to innovations and eventually solutions that will save lives," Tachi Yamada, of the Gates Foundation's global health program, said in a statement, according to Reuters. The winners are from 18 countries and were culled from universities, research institutes and non-profit organizations.

The sweat vaccine is from a group of German scientists who will use their grant to develop nanoparticles that can penetrate the skin through hair follicles. The nanoparticles will release vaccines by bursting upon contact with human sweat. Another project receiving funding is an imaging system that seeks to destroy parasites through a novel targeted laser vaccine.

Chief Mwanachingwala of Mazabuka has called on Government to intervene in the compensation of victims of failed microbicide trials in his kingdom. The chief said there was need for the microbicide development programme (MDP)to compensate the victims of its failed exercise who ended up contracting HIV/AIDS.

He was speaking in an interview at his palace during the week. He said the MDP recently called a meeting at Mulungushi International Conference Centre, which he attended but that there was no mention of compensation of the victims of the failed programme.

"From the look of things, it is like those people are not convinced that the trials failed and also that people contracted the HIV. We are just waiting for the experts to explain it all to us," he said.

He said he was willing to bring witnesses to testify what transpired during the trials and asked the Government to take interest in the matter. Chief Mwanachingwala said what transpired during the trials was clear hence the need for the Government to move in and ensure victims are compensated.

The National Aids Council says its statistics show more women are now willing to use the female condom, with commercial sex workers topping the list of users. Married couples, however, generally shun use of the female condom.

This year, NAC has recorded a 125 percent increase in use of both the male and female condom over last year's figures. This was revealed last week during a NAC-organised meeting with health stakeholders in Harare. The meeting evaluated behaviour change among men and women with regards to the use of condoms. The Ministry of Health, 2gether As One, Life Empowerment Support Organisation, Zimbabwe Community Health Intervention Research Project, Childhood HIV & Aids Zimbabwe, and the Harare City Council's social welfare department all highlighted progress with their behaviour change programmes.

A NAC survey reveals that commercial sex workers prefer the female condom to the male condom. Harare provincial NAC co-ordinator Mr Adonija Muzondiona said: "There is need for more awareness campaigns, community mobilisation and sensitisation on sexually transmitted diseases." Service providers achieved most of their behaviour change targets due to well-planned and co-ordinated programmes, but lack of funding remains a challenge to NAC and other stakeholders, Mr Muzondiona said.

A heralded clinical study in South Africa that assessed the best treatment strategy for people infected with HIV who are receiving drugs for tuberculosis should never have been done, argue two bioethicists in an online posting published 5 May by the Hastings Center, a bioethics research institute. The study, Starting Antiretroviral Therapy at Three Points in Tuberculosis, began in June 2005 and was stopped in September 2008 after an interim analysis found that people who delayed starting anti-HIV drugs until they completed a 6-to-8-month course of anti-TB medication had twice the risk of death. The prominent research group that ran the 642-person study immediately reported the findings, which led the World Health Organization to strengthen its guidelines.

Also see:
Timing of initiation of antiretroviral drugs during tuberculosis therapy (New England Journal of Medicine)
A study that should not have been done (Hastings Center)

Adjuvant effects on innate as well as adaptive immunity may be critical for inducing protection against mucosal HIV and simian immunodeficiency virus (SIV) exposure. We therefore studied effects of Toll-like receptor agonists and IL-15 as mucosal adjuvants on both innate and adaptive immunity in a peptide/poxvirus HIV/SIV mucosal vaccine in macaques, and made three critical observations regarding both innate and adaptive correlates of protection: (i) adjuvant-alone without vaccine antigen impacted the intrarectal SIVmac251 challenge outcome, correlating with surprisingly long-lived APOBEC3G (A3G)-mediated innate immunity; in addition, even among animals receiving vaccine with adjuvants, viral load correlated inversely with A3G levels; (ii) a surprising threshold-like effect existed for vaccine-induced adaptive immunity control of viral load, and only antigen-specific polyfunctional CD8+ T cells correlated with protection, not tetramer+ T cells, demonstrating the importance of T-cell quality; (iii) synergy was observed between Toll-like receptor agonists and IL-15 for driving adaptive responses through the up-regulation of IL-15Ra[alpha], which can present IL-15 in trans, as well as for driving the innate A3G response. Thus, strategic use of molecular adjuvants can provide better mucosal protection through induction of both innate and adaptive immunity.

WHO's 2009 report entitled Women and health ¹ contains a sentence that has unfortunately made headlines and been featured in a UNAIDS press release. ² "Globally, HIV is the leading cause of death and disease in women of reproductive age" (p 43). ¹ Although the estimated 682 000 HIV-related deaths of women aged 15-44 years exceed the 517 000 deaths from pregnancy-related causes and those due to other disorders except injuries (750 000), ³ the statement is misleading from at least two perspectives.

With several efforts underway to increase the local production of drugs in developing countries, Tatum Anderson assesses the pros and cons of manufacturing medicines in Africa.

A drugs producer in Uganda has become the first in a least developed country (LDC) - a category reserved for the world's poorest nations - to achieve a world-class seal of quality for its manufacturing standards. The Quality Chemicals plant, in the Ugandan capital Kampala, is the first to get this far along the so-called WHO pre-qualification process; a stringent quality check imposed on manufacturers of drugs. There are around 37 manufacturers in sub-Saharan Africa. "There has been excitement", says George Baguma chief marketing officer at Quality Chemicals. "We are the first in sub-Saharan Africa to get pre-qualification of a plant outside South Africa."

The next step is to gain approval, or pre-qualification, for each malaria and HIV/AIDS drug the firm produces, before international agencies, such as UNICEF, are allowed to buy from the company. It is an important milestone because of scepticism over domestic, or local manufacturing, in such countries, says Suerie Moon, an expert on local production at the Kennedy School of Government, Harvard University, MA, USA. "There is a lot of doubt in the global health community as to whether a firm in an LDC is capable of producing at WHO pre-qualification standards", she says. "It sends a clear signal that it's possible and is an important part of changing the way people think about local production."

A World Bank report set the tone in 2005, concluding that in many parts of the developing world, producing medicines domestically made little economic sense and could even end up reducing access to medicines. The thinking was that few developing world producers could compete with those from India and China. And, crucially, from a public health point of view it does not matter where the drug comes from as long as it is safe, affordable, and of good quality.

Application of any new biomarker to support safety-related decisions during regulated phases of drug development requires provision of a substantial data set that critically assesses analytical and biological performance of that biomarker. Such an approach enables stakeholders from industry and regulatory bodies to objectively evaluate whether superior standards of performance have been met and whether specific claims of fit-for-purpose use are supported. It is therefore important during the biomarker evaluation process that stakeholders seek agreement on which critical experiments are needed to test that a biomarker meets specific performance claims, how new biomarker and traditional comparators will be measured and how the resulting data will be merged, analyzed and interpreted.

The causes underlying unintended pregnancies are many and complex. But there is no doubt that the vast majority could be prevented by contraceptives that are already available and easily accessible. People just need to stick with them.

The pill is very effective. Only 1 in 1,000 women will get pregnant while taking the oral contraceptive if used perfectly...

As the number of new HIV infections continues to outstrip treatment capacity, the need for better prevention strategies becomes ever more apparent. Although attempts to develop an HIV/AIDS vaccine have been discouraging, other approaches to slow the spread of HIV are sparking interest, report researchers at the 17th Conference on Retroviruses and Opportunistic Infections. Studies are under way to assess whether a strategy known as "test and treat" - large-scale testing of individuals for HIV infection and initiating treatment with antiretroviral drugs in those who test . . .

In order to optimize health outcomes within the constraints of inevitably limited resources, low- and high-income countries alike require unbiased means of assessing health care interventions for their relative effectiveness. Such interventions include diagnostic tests and treatments (both established and newly developed) and implementation of health policy [1]. Likewise, health care professionals and patients need better information to inform health care decisions that require weighing benefits and risks in light of the patient's medical history and personal preferences.

Some countries and international organizations have recognized the need for such evidence and are already allocating funds for research to provide it [2]. The WHO Ministerial Summit in Mexico called for the establishment of support for a substantive and sustainable program of health systems research aligned with countries' priority needs and aimed at achieving internationally agreed-upon health-related development goals, including those contained in the United Nations Millennium Declaration [3]. The UK has established the National Institute for Health Research to commission and disseminate research that supports decision making by professionals, policy makers and patients and to ensure that the UK's health system, the National Health Service, has access to the best possible evidence to inform decisions and choices [4].

The US is now addressing similar goals with an initiative known as comparative effectiveness research (CER). In 2008, a report by the US Institute of Medicine (IOM) noted that patient care "should be based on the conscientious, explicit, and judicious use of current best evidence" [1]. In legislation that allocated US $1.1 billion in the US for CER on health care practices in 2009, the US Congress mandated that the IOM set national priorities for CER clinical topics. The IOM defined CER as "The generation and synthesis of evidence that compares the benefits and harms of alternative methods to prevent, diagnose, treat, and monitor a clinical condition, or to improve the delivery of care" [5]. The definition further stated that "The purpose of CER is to assist consumers, clinicians, purchasers, and policy makers to make informed decisions that will improve health care at both the individual and population levels."

Rumours of a gay wedding spark a riot at an HIV clinic in Kenya, closing it for two days; a pair of men who plan to wed are jailed for months without bail in Malawi; a law before the Ugandan parliament seeks to impose the death penalty for homosexual acts and would prosecute parents, colleagues, and healthcare workers for not immediately reporting people whom they think might be gay to the authorities. This is the face of homophobia that is imperilling the fight against HIV and AIDS in Africa. UNAIDS director Michel Sidibe, like his predecessor Peter Piot, has been adamant about tackling homophobia. It is unacceptable that 85 countries still have laws on the books criminalising sexual activity between adults and seven reserve the death penalty for homosexual acts, he told journalists in New York City in March.

Onyeabor's letter highlighted some of the ethical complexities inherent in posttrial access. Although we agree that ethically, individuals benefiting from antiretroviral therapy should continue to receive it, the challenge for all of us involved in the ethical conduct of research is to be clear about how this should occur. Many study participants in developing countries, including those in the studies cited, understandably feel that antiretroviral treatment should be continued for life.¹ Yet, in other studies, participants appeared to expect national programs to provide treatment, not necessarily the researchers themselves.²

Related articles in AJPH:
Planning for posttrial access to antiretroviral treatment for research participants in developing countries
Seema Shah, Stacey Elmer, and Christine Grady

We thank Helleringer and Reniers for their thoughtful response to our recent manuscript.¹ They point out several important challenges of interpreting the average, population-level effect of an individual-level exposure (HIV testing and counselling, or HTC) on an individual-level outcome (condom use). Our paper was a secondary analysis of data originally collected to measure the effect of hormonal contraceptive use on women's risk of HIV acquisition.² We used these data to quantify the change in Ugandan and Zimbabwean women's self-reported condom use both a short and longer time period after learning their HIV status.

Related articles in Int. J. Epidemiol.:
Study designs fail to represent the intricate effects of HIV testing and counselling on condom use and HIV transmission in sub-Saharan Africa
Helleringer S and Reniers G

Developing and disseminating a preventive HIV vaccine is a primary scientific and public health objective. However, little is known about HIV vaccine acceptability in the high-prevalence setting of South Africa - where young adults are likely to be targeted in early dissemination efforts. This study reports on six focus groups ( n = 42) conducted in 2007 with South Africans aged 18 to 24 years. A deductive framework approach is used to identify key motivators and barriers to future HIV vaccine uptake. Participants identify HIV testing, HIV stigma, mistrust of the health care system, and concerns about sexual disinhibition as barriers to vaccine uptake. For women, family members and friends are strong motivators for vaccine uptake, whereas men are more likely to see vaccines as an opportunity to stop using HIV prevention strategies such as condoms and partner reduction. Implications of these findings for developing HIV vaccine dissemination strategies and policy in South Africa are discussed.

Background.Few data on the effect of human papillomavirus (HPV) infection on human immunodeficiency virus (HIV) acquisition are available.

Methods.HIV-seronegative, sexually active, 18-24-year-old Kenyan men participating in a randomized trial of male circumcision provided exfoliated penile cells from 2 anatomical sites (glans/coronal sulcus and shaft) at baseline. The GP5+/6+ polymerase chain reaction assay ascertained a wide range of HPV DNA types at the baseline visit. The risk of HIV infection was estimated using Kaplan-Meier methods and hazard ratios from proportional hazards models.

Results.Of 2168 uncircumcised men with baseline HPV data, 1089 (50%) were positive for HPV DNA. The cumulative incidence of HIV infection by 42 months was 5.8% (95% confidence interval [CI], 3.6%-7.9%) among men with HPV-positive glans/coronal sulcus specimens, versus 3.7% [95% CI, 1.8%-5.6%] among men with HPV-negative glans/coronal sulcus specimens (P = .01). Controlling for subsequent circumcision status, baseline herpes simplex virus type 2 serostatus, and sexual and sociodemographic risk factors, the hazard ratio for HIV infection among men with HPV-positive glans/coronal sulcus specimens was 1.8 (95% CI, 1.1-2.9), compared with men with HPV-negative glans/coronal sulcus specimens.

Conclusion.The results suggest an independent increased risk of HIV seroconversion among HPV-positive men. If this finding is confirmed in other studies, HPV prevention could be another tool for HIV prevention.

Background/Objectives Commercial sex work is a primary context for heterosexual HIV/AIDS transmission. Violence victimisation is considered to compromise women's ability to protect against HIV and other sexually transmitted infections (STI); little research has investigated violence as it relates to sexual risk and STI among female sex workers (FSW). This study sought to compare sexual risk and STI symptoms among FSW based on recent violence exposure.

Methods Data from 815 FSW in Thailand were used to assess the prevalence of physical or sexual violence within the context of sex work, and associations of victimisation with sexual risk and STI symptoms.

Results Approximately one in seven FSW (14.6%) had experienced violence in the week before the survey. Compared with their unexposed counterparts, FSW exposed to violence demonstrated a greater risk of condom failure (19.6% vs 12.3%, ARR 1.92, 95% CI 1.24 to 2.95) and client condom refusal (85.7% vs 69.0%, ARR 1.24, 95% CI 1.14 to 1.35). In analyses adjusted for sexual risk, violence related to STI symptoms collectively (ARR 1.11, 95% CI 1.02 to 1.21) and genital lesions as an individual STI symptom (ARR 1.78, 95% CI 1.20 to 2.66).

Conclusion Physical and sexual violence against FSW in Thailand appears to be common, with women experiencing such violence demonstrating diminished capacity for STI/HIV harm reduction and greater prevalence of STI symptoms. Efforts to reduce violence towards this vulnerable population must be prioritised, as a means of protecting the health and wellbeing of FSW, and as a key component of STI/HIV prevention and control.

HIV transmission may be prevented by effectively suppressing viral replication with antiretroviral therapy (ART). However, adherence is essential to the success of ART, including for reducing HIV transmission risk behaviors. This study examined the association of nonadherence versus adherence with HIV transmission risks. Men (n=226) living with HIV/AIDS and receiving ART completed confidential computerized interviews and telephone-based unannounced pill counts for ART adherence monitoring. Data were collected between January 2008 and June 2009. Results showed that nonadherence to ART was associated with greater number of sex partners and engaging in unprotected and protected anal intercourse. These associations were not moderated by substance use. The belief that having an undetectable viral load leads to lower infectiousness was associated with greater number of partners, including nonpositive partners, and less condom use. Men who had an undetectable viral load and believed that having an undetectable viral load reduces their infectiousness, were significantly more likely to have contracted a recent STI. Programs aimed at testing and treating people living with HIV/AIDS for prevention require attention to adherence and sexual behaviors.

In recent decades, developing countries have sought to reduce their reliance on trade with the economically and politically dominant northern, or developed, countries, favoring instead South-South partnerships that synergize strengths and bolster competitiveness. Entrepreneurial firms in developing countries are increasingly aware of the opportunities in one another's markets, as is evident from the 12.5% increase in the rate of South-South trade each year¹.

Members of the team studying South-South entrepreneurial collaboration in health biotech. From left to right: Sachin Chaturvedi, May Sanaee, Magdy A Madkour, Wen Ke, Halla Thorsteinsdottir, Victor Konde, Tirso W Saenz, Monali Ray, Christina Melon, Nefertiti El-Nikhely, Heba Maram.

Emerging economies, such as China and India, have experienced unprecedented growth and increased global trade². Furthermore, developing countries have been setting up mechanisms to encourage increased trade with one another by establishing free trade zones, such as the Association of Southeast Asian Nations Free Trade Area, the Southern Common Market (Mercosur/Mercosul) in Latin America and the Common Market for Eastern and Southern Africa.

Developing countries have also been targeting science and technology sectors as key areas for encouraging South-South collaboration and are forging a growing number of bilateral, multilateral and regional agreements with this aim³. South Africa and Malawi, for example, have formed an agreement directed at accelerating economic growth and reducing poverty through the adoption of current global technologies⁴. In addition, there are significant science and technology components in regional collaboration efforts in developed countries, such as those organized by the New Partnership for Africa's Development (http://www.nepad.org/), and the IBSA network organized by India, Brazil and South Africa (http://www.ibsa-trilateral.org/). Health biotech provides a substantial scope for collaboration between developing countries as several developing countries have built up capacity in the field, including private-sector development^{5, 6, 7, 8, 9}.

Background Pre-exposure prophylaxis (PrEP) is a promising new HIV prevention method, especially for women. An urgent demand for implementation of PrEP is expected at the moment efficacy has been demonstrated in clinical trials. We explored the long-term impact of PrEP on HIV transmission in different HIV epidemics.

Methodology/Principal Findings We used a mathematical model that distinguishes the general population, sex workers and their clients. PrEP scenarios varying in effectiveness, coverage and target group were modeled in the epidemiological settings of Botswana, Nyanza Province in Kenya, and Southern India. We also studied the effect of condom addition or condom substitution during PrEP use. Main outcome was number of HIV infections averted over ten years of PrEP use. PrEP strategies with high effectiveness and high coverage can have a substantial impact in African settings. In Southern India, by contrast, the number of averted HIV infections in different PrEP scenarios would be much lower. The impact of PrEP may be strongly diminished or even reversed by behavioral disinhibition, especially in scenarios with low coverage and low effectiveness. However, additional condom use during low coverage and low effective PrEP doubled the amount of averted HIV infections.

Conclusions/Significance The public health impact of PrEP can be substantial. However, this impact may be diminished, or even reversed, by changes in risk behavior. Implementation of PrEP strategies should therefore come on top of current condom campaigns, not as a substitution.

More people today have access to life-saving antiretroviral therapy for HIV/AIDS than ever before. Yet for every person who begins treatment for HIV infection, two to three others become newly infected. Treatment alone will not curtail the HIV/AIDS pandemic. To control and ultimately end this pandemic, we need a powerful array of proven HIV prevention tools that are widely accessible to all who would benefit from them.

Vaccines historically have been the most effective means to prevent and even eradicate infectious diseases. They safely and cost-effectively prevent illness, disability and death. We at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, have been working for more than two decades with our colleagues worldwide to develop an HIV vaccine, and this research continues to rank among our top priorities.

National HIV Vaccine Awareness Day marks an opportunity to reflect on our progress, renew our commitment to finding an HIV vaccine, and personally thank the scientists, community educators, health care workers, and especially the many study volunteers who have dedicated their time and energy to this important endeavor. Only with the continued commitment of volunteers may we more effectively confront the global scourge of HIV/AIDS and pursue the goal of an HIV vaccine.

We have witnessed significant progress in HIV vaccine research during the past year. Notably, a major clinical trial in Thailand gave us the first indication that an experimental vaccine can protect some humans against HIV infection (http://www.niaid.nih.gov/news/newsreleases/2009/Pages/ThaiVaxStudy.aspx). With the participation of more than 16,000 volunteers, investigators found the vaccine to be 31 percent effective at preventing HIV infection. Although this level of protection is modest, it gives us hope that a safe and effective HIV vaccine is possible. The priority now is to try to understand how the vaccine induced protection against HIV infection in some individuals, and to build on those results.

The Thai trial demonstrated the power of large-scale clinical trials to advance HIV vaccine development and to answer fundamental scientific questions. Such trials are possible only through strategic partnerships among federal collaborators, nongovernmental organizations and the private sector. NIAID continues to pursue focused clinical HIV vaccine research through such partnerships.

An intensive training course for academics and researchers from low- and middle-income sub-Saharan African countries (see full eligibility criteria). The course will address essential conceptual, methodological, and practical issues inherent in planning and conducting community engagement and community-partnered public health research with a communicable and non-communicable disease focus, specifically human immunodeficiency virus (HIV), tuberculosis (TB), cancer, diabetes and cardiovascular disease (CVD).

Dates:
August 3-6, 2010 in Johannesburg, South Africa
August 10-13, 2010 in Durban, South Africa

Presolicitation Notice Information
The discovery and development of an AIDS vaccine is among the highest research priorities of the National Institute of Allergy and Infectious Diseases (NIAID), and among the principal missions of NIAID's Division of AIDS (DAIDS). To support this mission, the incumbent Contractor provides high quality, novel, and targeted reagents, assays and services for use by the HIV/AIDS vaccine research community. Specific projects have included producing, purchasing and providing overlapping peptide sets for SIV/SHIV and HIV, polyclonal and monoclonal antibodies, procuring SIV and SHIV challenge stocks, and supporting the repeated and extensive proficiency testing/standardization of the widely used TZM-bl neutralization assay.

The purpose of the proposed contract will be to produce, procure, store, ship, and maintain an up-to-date inventory of high-quality reagents and assays in support of preclinical and clinical AIDS vaccine research. To fulfill the technical requirements, the Contractor shall: 1) procure, purify, and test reagents for the DAIDS Vaccine Research Program, including, for example: viral proteins and peptides, virus stocks, monoclonal and polyclonal antibodies, topical microbicides, vaccine vectors, vaccine adjuvants and cytokines, and any additional reagents deemed necessary for the NIAID DAIDS Vaccine Research Program; 2) perform genetic cloning and sequencing; 3) acquire the needed reagents, assays, and/or services used to evaluate AIDS vaccine safety and immunogenicity; 4) analyze all reagents for purity and integrity, and provide for their quality control and assurance; and 5) provide for receipt and inventory tracking, storage, maintenance, and distribution of all reagents.

Date: 17 May 17 2010
Host: Aeras Global TB Vaccine Foundation, Global Health Council, Global HIV Vaccine Enterprise, HIV Vaccine Trials Network, International AIDS Vaccine Initiative, Jenner Society, PATH Malaria Vaccine Initiative, US Military HIV Research Program, US Military Malaria Vaccine Research Program, Vaccine Research Group, Mayo Clinic, and the It's Time Campaign.
Location: Rayburn House Office Building, Washington, DC

A draft of the National Security Council's document on US global development policy, recently published in Foreign Policy's "The Cable," reveals several vital and promising developments in foreign assistance reform. The document, which outlines details from the Presidential Study Directive-7, recognizes that research and development of new tools is critical to reaching overall US development goals. The document lists investing in "game-changing innovations with the potential to solve longstanding development challenges" as one of its five pillars, with a focus on increasing public- and private-sector funding for development research, fostering innovation, and capitalizing on new and sustainable models to develop new tools such as vaccines.

May 24 from 9:30 a.m. - 11 a.m. ET: The Kaiser Family Foundation will hold a policy forum at their Washington, D.C. office to look at the progress in reaching Millennium Development Goals 4 and 5, and the evolving U.S. role in improving maternal and child health in developing countries.

Renewed attention by the global community to improve maternal and child health worldwide is creating the potential for significant progress in the coming years.  In the United States, the U.S. government also has increased its focus on tackling the high rates of maternal and child mortality in the developing world through the administration's Global Health Initiative, which includes specific maternal and child health targets and addresses other health challenges affecting women and girls, including family planning and reproductive health. 

The expert panel discussion will include Jennifer Klein, senior advisor on global women's issues at the U.S. Department of State; Flavia Bustreo, director, Partnership for Maternal, Newborn and Child Health, World Health Organization; Ana Langer, president, EngenderHealth; Christopher J.L. Murray, director of the Institute for Health Metrics and Evaluation at the University of Washington; and Jen Kates, vice president and director of Global Health Policy and HIV, Kaiser Family Foundation.  Foundation Executive Vice President Diane Rowland will moderate.

NOTE: Following the Kaiser policy event, there will be a symposium co-hosted by The Lancet and IHME featuring key maternal and child health experts in a scientific dialogue around the data and analytic approaches in estimating maternal and child mortality around the world. For details about that session, contact Summer Ohno at slohno@uw.edu.