4 JUNE 2010, VOLUME 11, ISSUE 19

One of the most contentious issues in HIV prevention trials has been the question of who is responsible for the care of people who become infected during the trial, and whether they are entitled to compensation. Two presentations at the Microbicides 2010 Conference investigated what actually happened to women who seroconverted during the two trials of the candidate microbicide PRO 2000.

Sharon Riddler of the University of Pittsburgh analysed what happened to women who had seroconverted (become HIV positive) during the HPTN 035 study, the smaller of the two trials. There were 3087 women in this trial, of whom 139 (4.5%) seroconverted. One hundred of them are currently in an ongoing prospective cohort called MTN 015, which will analyse the care received by seroconverters not just in the HPTN 035 trial but also the CAPRISA and VOICE trials of tenofovir microbicides and pre-exposure prophylaxis.

The world needs to prepare for a resurgence of HIV drug resistance if pre-exposure prophylaxis is widely adopted, a veteran HIV researcher warned the Microbicides 2010 Conference last week. Dr John Mellors of the University of Pittsburgh has studied the dynamics of viral suppression and how drug resistance arises since the beginning of HIV therapy. He admitted that, so far, "there are highly divergent opinions on whether PrEP will spread resistance." There is only one person in a PrEP trial with documented seroconversion while taking PrEP whose drug resistance was measured and this person turned out to have non-resistant 'wild type' virus.

There are particular challenges to encouraging and accurately measuring adherence in research trials of pre-exposure prophylaxis (PrEP), researchers reported in a series of presentations at the Fifth International Conference of HIV Treatment Adherence in Miami this week. Participants feel healthy but associate pill-taking with being sick, the drugs link the person with HIV infection, and admitting to missing doses can be challenging. As the research studies are investigating whether once-a-day Truvada helps prevent HIV infection or not, optimal adherence will help researchers answer this question. Nonetheless, one study's principal investigator questioned whether adherence to once-a-day treatment will ultimately be expected of people taking PrEP, should it work.

Pre-exposure prophylaxis (PrEP) is the use of antiretrovirals prior to exposure to HIV to prevent infection. PrEP is intended for use by people who may be at frequent risk for HIV and a series of studies known as iPrEx are being conducted among men who have sex with men in six countries. Adherence is being measured in the iPrEx studies through pill counts, self-report during an interview with a staff member, self-report through computer-assisted self-interview (CASI), testing of drug levels in the blood and testing of drug levels in hair (in a smaller sub-study). Data on actual levels of adherence will be presented at a later date.

HIV and Aids researchers from across the world are hopeful there will be breakthroughs in two years that will bring a glimmer of hope to people infected with the virus.

Speaking at the International Microbicide Conference that ended in Pittsburgh last week, Pro-Vice Chancellor of the University of KwaZulu Natal in South Africa Dr Salim Abdool Karim was optimistic that by 2012, technological developments would enable researchers to tell if participants of current research were adhering to trial drugs. Prof Karim said: "Currently, there is no way we can tell that these participants are adhering to their drugs except to take participant's word of mouth and this really affects the results. "We hope technological developments will speed up the whole process of conducting clinical trials and gathering information from participants."

Leading Zimbabwean researcher Professor Mike Chirenje, who is working with the University of Zimbabwe in collaboration with the University of San Francisco in California, was confident that the next two years would prove or disprove the safety of microbicides use in pregnant women. "We do not know if microbicide use is safe in pregnant women. Several studies are currently underway to determine if the use of these chemicals is safe for development of the foetus. Results of these studies are expected before 2012," Prof Chirenje said.

A large number of presentations at the Microbicides 2010 Conference in Pittsburgh documented the development of microbicides very different from gels or creams. Vaginal rings, quick-dissolve pills and thin films smaller than sticks of gum are all being tested. Poor adherence was probably one of the reasons the last few efficacy trials of microbicides failed, and there is clearly an urgent need to develop formulations that do not require daily adherence or to be applied every time before sex, and which are also convenient and portable.

The International Partnership for Microbicides (IPM), the largest and best-funded microbicide research programme, clearly believe that lower-frequency products are the way ahead, because they are now devoting the biggest slice of their budget to developing vaginal rings that sit on the cervix and slowly deliver antiretroviral drugs over a period of a month. Vaginal rings have been used before to deliver contraceptives. Researchers so far have measured absorption and delivery rates of rings made of different plastics and have completed an acceptability trial of an inert, non-drug-containing ring in HIV-negative women.

"Antiretroviral microbicides for prevention -- such promise needs urgent research. How can I stand idly by and not take up this challenge?" asks Professor Salim "Slim" Abdool Karim, Head of the Centre for AIDS Programme of Research in South Africa (CAPRISA). He was eferrring to Caprisa 004, a trial that is currently testing the effectiveness of a tenofovir-based microbicide. Lungi Langa spoke to Karim at the recent Microbicide conference in Pittsburgh.

How did you get involved in Microbicide research? My wife (Quarraisha) and I are both involved in microbicide research. Our background knowledge and introduction to microbicides was through Zena Stein who published a seminal paper entitled "HIV Prevention: The Need for Methods Women Can Use" in the American Journal of Public Health. She is the "mother" of microbicides. Her passion was to launch a project of a microbicide that would be woman controlled and effective.  She mentored my wife and I. It was her interest that got us involved in microbicides research.

How long have you been in microbicide research? We have both been involved in microbicide research for over 14 years. In 1989 we decided to focus our research on HIV prevention. In 1996, we started a study to test the effectiveness of Nonoxynol-9. We got a call from a health inspector in Ladysmith, who wanted help with prevention messaging for sex workers in the area. We drove there one day to see if we could help and met with the sex workers. When we got there we saw several trucks and one-by-one the sex workers arrived for their meeting with us. It was a remote area but there so many of them. It was in a small town. We didn't know where they were coming from. We met with the sex workers and gave a talk about HIV prevention. They were interested in the information.  We approached them with an idea for our study to help prevent HIV infection and asked them if they were interested in participating in it. They wanted to participate if one of them could be allowed to liaise on their behalf. One of the women was trained on prevention and worked with us. We did the study and from then we got involved in many other trials including Pro2000 more recently Caprisa 004.

I am back from a trip I am finding difficult to narrate to my children. The conference in Pittsburgh, USA, was about microbicides, a gel that is being tested in humans to kill HIV on spot. It is applied into the vagina and has shown more exciting success in animals than Nambooze's victory in Mukono. The success of microbicides in humans would be a welcome addition to the already existing prevention technologies like condoms, circumcision and MP Winfred Kiiza's slaps.

The US conference was very successful in all fronts, including the use of the word vagina. My problem was that, because I am culturally unsophisticated, the V word makes me want to look behind my shoulders first. In Pittsburgh, it was all over the place. Everywhere I turned, looked or sniffed; in every sentence, on notice boards, computers, messages, announcements, posters, people's mouths, people's bodies etc, the word vagina was galore! Had I not gotten used to the rate at which it was being released to the environment in the first hour, I would have twisted my neck.

The Treatment Action Campaign (TAC) has urged President Jacob Zuma to advocate universal access to HIV treatment, prevention and care when he meets other Group of 20 (G-20) leaders in Canada later this month. The AIDS lobby group sent a letter to Mr Zuma on Friday urging him, as president of the only African member of the G-20, to speak for the entire region and other developing countries. The organisation also wrote to US Vice-President Joe Biden requesting a meeting with him when he comes to SA for the World Cup. The meeting is intended to centre on concerns that the US is backing away from its commitments on HIV/AIDS. The two letters, signed by TAC general secretary Vuyiseka Dubula, come at a time of reduced global funding for HIV. The organisation said the US was turning away from the President's Emergency Plan for AIDS Relief (Pepfar), established in 2003 by former president George Bush, in favour of the new Global Health Initiative, which some claim has broadened the mandate of health intervention without expanding funding, thus resulting in less money for HIV.

A research finding has revealed that using anti-retroviral drugs (ARVs) to prevent HIV could result in drug resistance if routine screening is not done. This was the finding of a study circulated at the ongoing M2010 conference at David Lawrence Convention Centre here, in asking whether drug resistance could be a problem if ARVs became the mainstay for HIV prevention. Ume Abbas, who led a team of researchers, had developed a model to simulate the impact of pre-exposure prophylaxis (Prep) on HIV prevention and drug resistance in the sub-Saharan region, where HIV prevalence is highest, and to identify the determinants contributing mostly to HIV drug resistance. "That resistance could happen if people who are unknowingly already infected use the approach, so it is important for people to know their status before resorting to any drug intake," Dr Abbas said. The results of these studies underscore the importance of incorporating routine HIV testing and the on-going monitoring of infection status in any prevention programme that involves the use of ARVS. Prep, as the approach is called, involves the use of ARVS by HIV-negative people in order to reduce their risk of infection. With Prep, a single ARV is used typically once a day while one ARV has the potential to prevent HIV in someone who is not infected with the virus.

The world's first herpes-killing vaginal gel may go on sale within two years, said its developer Starpharma Holdings Ltd., which plans to start patient studies on its effectiveness. Starpharma is in discussions with "a number of groups" about trials of its VivaGel product in women at risk of contracting genital herpes, Chief Executive Officer Jackie Fairley said in an interview in Singapore, declining to identify the partners. The Melbourne-based company licensed its VivaGel-coated condoms in 2008 to SSL International Plc, maker of the world's best-selling Durex brand. No cure exists for genital herpes, a condition that infects about one in six Americans and produces painful sores and increases HIV transmission, U.S. Centers for Disease Control and Prevention data show. While other gels are being developed to prevent HIV infections, VivaGel is the only microbicide designed to stop herpes from spreading, Fairley said.

After years of what often seemed like an impossible pursuit, Aids vaccine researchers have a renewed sense of hope. To commemorate World Aids Vaccine Day recently, the International Aids Vaccine Initiative (IAVI) screened a new documentary, H is for Human, and hosted a panel discussion on Aids vaccine research at Vega School in Randburg. The panel of experts lauded the results of a study conducted in Thailand last September when an experimental vaccine prevented HIV infection in 30 percent of subjects. This marked the first major breakthrough in effective Aids vaccines tested on human candidates. Thirty percent might not sound like much, said Dr Eftyhia Vardas, an associate professor at the University of Stellenbosch, but when 7 500 people worldwide were newly infected with the virus every day, the vaccine could protect 2 500 of those people. Since 1997, vaccine researchers had struggled against this "incredibly clever" virus that attacks the very cells that are supposed to defend against disease, she said. "To be honest, many of us were secretly skeptical (about finding the vaccine)," said Dr Linda-Gail Bekker, researcher at Desmond Tutu HIV Centre in Cape Town. "But the Thai study has changed the face of HIV vaccinology forever."

More women than men in Nyanza Province associate male circumcision with HIV prevention although awareness of the procedure is high among both genders. This was contained in the results of a survey by the National Aids and STD Control Programme and Unicef. The survey carried out by Infotrak Research and Consulting across eight districts in Nyanza Province, had a total of 1,940 men and 290 women interviewed. "When the respondents were asked about what male circumcision meant, 38 per cent of the women associated the procedure with HIV prevention, compared to 28 per cent of the men. Ninety-four per cent of both men and women identified male circumcision as the cutting of the foreskin," said the report. The findings of the survey are contained in the Male Circumcision Consortium newsletter.

At least 6000 men have been circumcised in a pilot project which the ministry of health has been carrying out with the government setting up a national campaign of the program which is likely to reduce country's HIV prevalence to a single digit, a senior health practitioner has said. Currently the HIV prevalence is at 13.7%. Speaking to ZimEye in Harare on Friday, Specialist Urologist who is also Vice President of the colleges of Surgeons of East, Central and Southern Africa Arusha Tanzania, Mr Christopher Samkange said that lack of funding is disturbing the national rolling of the male circumcision program which has proved to reduce HIV prevalence to a single digit. "We have carried out a practical model that has proved that male circumcision has the impact that we are aiming to, that (is) to reduce HIV prevalence from double digits to single digit; and for us do achieve that we must circumcise 80% of the male population in the country," said Samkange.

Contrary to reports from some sections of the media that circumcision was facing tense resistance Samkange said the government was actually failing to attend to a huge number of males who are waiting to be circumcised. "We carried out a feasibility study that showed us that the circumcision operations can be done and we set up five centers in the country which we have used as a model to see how best it can be done and it is in these five centers in the pilot phase that have produced the 6000 males that have so far been circumcised. "We have now learnt on how best we can do the operations and now rolling out a national circumcision program,"said Mr Samkange.

On a recent trip to Mozambique, Jeffrey Raikes, CEO of the Bill & Melinda Gates Foundation, cornered two rice farmers for a chat. Both farmed in the same area, on different parts of the same river, growing the same variety of rice. Yet one farmer had yields larger than the other, Raikes recalls.

Raikes walked away wondering why -- and not because he grew up on a farm in Nebraska -- but because such answers may help the Gates Foundation help other rice farmers improve crop yields and aid the foundation in meeting its goal to help 150 million of the world's poorest families lift themselves out of extreme poverty by 2025. "Our success will come from listening and learning from others," Raikes says.

Raikes, who worked in Bill Gates' inner circle at Microsoft for 27 years, is often described by colleagues as a "great listener." But that's not always the description used for the Gates Foundation, the world's biggest philanthropic organization, with an endowment of $35 billion -- about three times more than the second-biggest in the U.S., the Ford Foundation. Last year, the Gates Foundation gave away $3 billion. That's an amount on par with the individual gross domestic product that year of almost three dozen countries, including Togo and Swaziland.

Instead, the Gates Foundation has been painted by critics and even admirers as sometimes too heavy-handed in saying how its money is used and too prone to listening to the recommendations of experts vs. grass-roots groups when setting its strategies to battle global poverty. "There's concern that their programs are too top down and they don't listen to the grass roots," says Pablo Eisenberg, senior fellow of the Georgetown Public Policy Institute. The institute, which is part of Georgetown University, focuses on research and an array of public policy issues.

Supporters of three HIV-positive women in Namibia who say they were sterilized without their consent held protests to support the women's decision to sue the government, a legal aid group said Wednesday. The Legal Assistance Center said protesters began staging sit-ins at two state hospitals in the southern African nation on Wednesday. The three women allege they were sterilized without their consent, and that the sterilization violated their rights to have children and not to be discriminated against. The women are seeking damages at a High Court hearing scheduled for Friday. Protest organizers said the sit-ins will continue until after the hearing, the first legal challenge of its kind in Namibia. The government maintains the women gave their consent and says it will fight the damages claim.

People living with HIV must take their place at the forefront of HIV prevention efforts in Kenya if they are to be truly successful, senior government officials said at the launch of a set of national guidelines for rolling out "Prevention with Positives" in the capital, Nairobi. "We have focused so much on empowering HIV-negative people to avoid infection. We now need to focus on people who are already infected and empower them to prevent new infections, re-infection, and maintain their own and their partners' good health," said Dr Nicholas Muraguri, head of the National AIDS and Sexually Transmitted Infections Control Programme.

One of the main aims of the guidelines is to ensure that all HIV-positive Kenyans are aware of their status; government statistics show that 84 percent of HIV-positive people do not know they are infected. "We want to de-stigmatise the HIV test so that HIV testing becomes a 'kawaida' [usual] thing," he said.  "At one point, every adult with sexually transmitted HIV was the HIV-negative partner in a discordant relationship," Muraguri said. "Over 44 percent of married HIV infected partners have an HIV-negative partner -- if they are aware of their status, they can take steps to protect their partners from infection."

People with HIV reduced the risk of handing on the AIDS virus by an astonishing 92 percent while they were taking antiretroviral drugs, according to a trial reported on Thursday. The research provides the strongest evidence to date that drugs which treat the human immunodeficiency virus could also be incorporated into strategies for fighting HIV's spread.

In a paper published by the British journal The Lancet, doctors recruited 3,381 heterosexual couples in seven African countries. Each couple was "serodiscordant," meaning that one of the pair was infected with HIV while the other was uninfected. Antiretroviral drugs were given to 349 individuals after their immune system, as measured by the numbers of CD4 cells, plunged below a given threshold. The other infected individuals received a dummy pill called a placebo. The researchers took blood samples from the other partner every three months to see whether he or she had become infected. The trial was closely monitored by an ethics committee, and included a training course in safe sex as well as routine health checkups.

After 24 months, 103 partners who had been HIV-free at the start of the experiment had become infected with the virus by their partner. But only one of these 103 transmissions was caused by a partner who was on antiretrovirals. The results were confirmed by genetic fingerprinting of the virus, showing whether it had been passed on by an infected partner or by someone from outside the trial. All in all, taking antiretroviral therapy (ART) reduced the risk of infecting someone else by 92 percent, a whopping fall that highlights the potential of these drugs as a weapon to prevent HIV, rather than just treat it, say the authors. "Provision of ART to HIV-1 infected patients could be an effective strategy to achieve population-level reductions in HIV-1 transmission," says the paper.

The government is set to launch the National Safe Male Circumcision (SMC) policy next month which will enable youth get free circumcision services, an official from the Health ministry has said. The policy will give priority to teenagers between the ages of 15 to 25 years. Highlighting the draft national policy on safe male circumcision as an alternative HIV control measure in Kampala yesterday, the assistant commissioner National Disease Control in the Ministry of Health, Dr Alex Opio, said the policy will enforce the law on safe male circumcision as a means of reducing the transmission of HIV/AIDS and other sexually transmitted diseases. But Dr Opio warned that the resumption of sex before complete healing of the wound may increase the risk of acquisition of HIV infection among the recently circumcised people.

Now that Uganda's donors are cutting funding for Aids drugs, the authorities may have to talk more about prevention and less about treatment. It is time to recall the 1990s, reports Rodney Muhumuza.

One of the patients at the Joint Clinical Research Centre is a well-educated man who first sought treatment for Aids in 1991, when he was a young boy, when most Ugandans were still deciding whether the disease usually called silimu was for real. This was the year of Yoanna Nanyonga, the Masaka woman who fed Aids sufferers on soil, offering dirt as a cure for the affliction. "He was a kid then," Dr Peter Mugyenyi, who runs the Joint Clinical Research Centre (JCRC), said of the man. "He now has a master's degree." This patient is one of at least 34,000 Ugandans who access anti-retroviral treatment, or ARVs, through JCRC, which started providing Aids drugs long before most Ugandans knew there was even treatment for the disease.

By 2003, when the JCRC's activities were becoming widely known, the institution had 72,000 patients, making it the biggest provider of ARVs in Uganda. But the times have changed, and it seems JCRC will be left behind. In excess of 100,000 Ugandans get infected with HIV every year, while only 200,000 of the 400,000 Ugandans who urgently need ARVs access them. Now, even as more Ugandans come forward to seek treatment, foreign donors, who have kept alive most of these Aids sufferers, are staring into what seems like a bottomless pit.

They are walking away, only guaranteeing that there will be money to treat those already in the system, people like Dr Mugyenyi's success story from 1991, the physician told Sunday Monitor in a recent interview. "The money has not been forthcoming," Dr Mugyenyi said. "A crisis is building up.... The US Presidential Emergency Plan for Aids Relief have said that all patients who are already on treatment will continue to get support. We don't have a budget for new patients."

Revealed: The men who covered their faces and made different poses in Mbabane belong to theatre group Pelepele, and were commissioned by PSI to market male circumcision. Yesterday, Litsemba Letfu Male clinic, a sister organisation to Population Service International (PSI), unveiled the group as part of their marketing strategy. During the unveiling half of the 10 group members had uncovered their faces -- something that the group's artistic director, Ncamiso Nthsangase, said was to show what happens when you have been circumcised.

"When we covered our faces people would come to us, wanting to touch, poke and pose with us. They had no idea who we were. Today we have partly uncovered our faces and now people can't come and don't want to poke or touch us. They are now able to put a face to the mysterious figure that made poses in town. This, in our view, is what happens when you are not circumcised as well as when you are circumcised. When you are not circumcised you are blind, you make yourself vulnerable to a number of things," Ntshangase said. He also said this form of theatre was popular and well known world-wide save for Swaziland.

Malawi's president on Saturday pardoned a gay couple who had been sentenced to 14 years in prison and ordered their release but insisted that homosexuality was still illegal in his conservative southern African nation. President Bingu wa Mutharika announced the pardon on "humanitarian grounds only" during a press conference with U.N. Secretary-General Ban Ki-moon in Lilongwe, the capital.

"These boys committed a crime against our culture, against our religion, and against our laws," Mutharika said. "However, as head of state, I hereby pardon them and therefore order their immediate release without any conditions." But he added, "We don't condone marriages of this nature. It's unheard of in Malawi and it's illegal."

Malawi had faced international condemnation for the conviction and harsh sentencing of Tiwonge Chimbalanga and Steven Monjeza, who were arrested in December, a day after celebrating their engagement.

We reviewed the potential impact of new WHO criteria for antiretroviral therapy using data from 1025 HIV-infected women and infants followed for 24 months in Lusaka, Zambia. The new criteria require initiating therapy among 68% of pregnant women and, if fully effective, would prevent 92% of maternal deaths and 88% of perinatal and postnatal infections. Using CD4 cell count below 350 cells/microlitre, irrespective of clinical stage, is more efficient and stricter CD4 cutoffs would be counter productive.

Objective: To conduct a systematic review of the literature to examine HIV vaccine acceptability and factors impacting acceptability of future HIV vaccines. Design: Systematic review and meta-analysis of peer-reviewed articles that assessed HIV vaccine acceptability. Methods: We used a comprehensive search strategy across multiple electronic databases to locate original quantitative or qualitative studies that examined rates or correlates of HIV vaccine acceptability. We conducted meta-analysis on studies reporting correlates or predictors of HIV vaccine acceptability. Results: Twenty studies (n = 7576) reported HIV vaccine acceptability ranging from 37.2 to 94.0 on a 100-point scale; weighted mean acceptability = 65.6 (SD = 21.1). Eleven studies compared HIV vaccine acceptability at high (80-95%) efficacy (mean = 73.8; SD = 9.2) versus moderate (50%) efficacy (mean = 40.4; SD = 20.2). Among 13 studies (n = 5023) included in meta-analysis, efficacy and non'risk group' membership had medium effect sizes, and pragmatic obstacles, cost, perceived susceptibility to HIV infection, side effects/safety concerns, fear of vaccines, perceived vaccine benefits, duration of protection, and ethnicity had small effect sizes on HIV vaccine acceptability. Conclusion: Public health strategies to promote the benefits of partial efficacy HIV vaccines and accurate HIV risk perceptions, and to dispel vaccine fears, along with structural interventions to subsidize vaccine costs and facilitate access, may increase future HIV vaccine uptake and, in turn, the effectiveness of HIV vaccines in controlling the epidemic.

Objectives: Preexposure prophylaxis (PREP) is an emerging HIV prevention strategy; however, many fear it may lead to neglect of traditional risk reduction practices through behavioral disinhibition or risk compensation. Methods: Participants were 180 HIV-negative high-risk men who have sex with men recruited in New York City, who completed an Audio Computer Assisted Self Interview-administered survey between September 2007 and July 2009. Bivariate and multivariate logistic regression models were used to predict intention to use PREP and perceptions that PREP would decrease condom use. Results: Almost 70% (n = 124) of participants reported that they would be likely to use PREP if it were at least 80% effective in preventing HIV. Of those who would use PREP, over 35% reported that they would be likely to decrease condom use while on PREP. In multivariate analyses, arousal/pleasure barriers to condom use significantly predicted likelihood of PREP use (odds ratio = 1.71, P < 0.05) and risk perception motivations for condom use significantly predicted decreased condom use on PREP (odds ratio = 2.48, P < 0.05). Discussion: These data provide support for both behavioral disinhibition and risk compensation models and underscore the importance of developing behavioral interventions to accompany any wide-scale provision of PREP to high-risk populations.

To close the gap between research and development, a number of funding organizations focus their efforts on large, translations research projects rather than small research teams and individual scientists. Yet, as Paul van Helden argues, if the support for small, investigator-driven research decreases, there will soon be a dearth of novel discoveries for large research groups to explore. To close the gap between research and development, a number of funding organizations focus their efforts on large, translations research projects rather than small research teams and individual scientists.

Objective To estimate the risk and probability of heterosexual transmission of HIV-1 from infected people taking combined antiretroviral treatment. Design Cross sectional and prospective cohort studies. Setting HIV clinic in Madrid, Spain. Participants Stable heterosexual couples with one partner with HIV-1 infection (index partner) and the other reporting this sexual relationship as the only risk exposure. Main outcome measures HIV seroprevalence in non-index partners at enrolment and seroconversions in follow-up according to antiretroviral treatment taken by the index partner. Results In 476 couples in which the index partner was not taking antiretroviral treatment, HIV seroprevalence at enrolment in non-index partners was 9.2% (n=44), whereas in 149 couples in which the index partner was taking combined antiretroviral therapy no partner was infected (P<0.001). During follow-up, the 341 serodiscordant couples in which the index partner was not taking antiretroviral treatment had about 11 000 acts of intercourse without condoms, 50 natural pregnancies, and five HIV seroconversions (0.0004 per unprotected intercourse; 95% confidence interval 0.0001 to 0.0010); 294 of these couples always used condoms, accounting for about 42 000 acts of intercourse, 136 risk exposures from condom failure, and one HIV seroconversion. The relative risk associated with condom use was 0.07 (0.01 to 0.58). In 144 couples the index partner was taking combined antiretroviral treatment; they accounted for over 7000 unprotected acts of intercourse and 47 natural pregnancies but no HIV seroconversion (0 to 0.0005 per unprotected intercourse). Conclusions The heterosexual infectivity of HIV-1 in individuals taking effective antiretroviral treatment is low. Avoidance of unprotected intercourse and receipt of antiretroviral treatment by the infected partner in accordance with protocols are complementary measures to prevent HIV transmission.

See related commentary in British Journal of Medicine: "HIV transmission in serodiscordant heterosexual couples"

Limited data are available on circumcision prevalence and acceptability among Thai men to prevent human immunodeficiency virus. Of 408 high-risk heterosexual men, 12.3% were circumcised. 14.2% and 24.9% expressed willingness to be circumcised before and after circumcision education, respectively. Neonatal circumcision acceptability was relatively high. One participant underwent circumcision at 3-month follow-up.

In this article we summarize several recent major developments in human immunodeficiency virus treatment, prevention, outcome, and social policy change. Updated international guidelines endorse more aggressive treatment strategies and safer antiretroviral drugs. New antiretroviral options are being tested. Important lessons were learned in the areas of human immunodeficiency virus vaccines and microbicide gels from clinical studies, and additional trials in prevention, especially pre-exposure prophylaxis, are nearing completion. Insight into the role of the virus in the pathogenesis of diseases traditionally thought to be unrelated to acquired immunodeficiency syndrome has become a driving force for earlier and universal therapy. Lastly, we review important achievements of and future challenges facing China as she steps into her eighth year of the National Free Antiretroviral Treatment Program.

Microvirin (MVN), a recently isolated lectin from the cyanobacterium Microcystis aeruginosa PCC7806, shares 33% identity with the potent anti-HIV protein cyanovirin-N (CV-N) isolated from Nostoc ellipsosporum and both lectins bind to similar carbohydrate structures. MVN is able to inhibit infection by a wide variety of HIV-1 laboratory-adapted strains and clinical isolates of different tropisms and subtypes in peripheral blood mononuclear cells (PBMCs). MVN also inhibits syncytium formation between persistently HIV-1-infected T cells and uninfected CD4+ T cells and inhibits DC-SIGN-mediated HIV-1 binding and transmission to CD4+ T cells. Long term passaging of HIV-1 exposed to dose-escalating concentrations of MVN resulted in the selection of a mutant virus with 4 deleted high-mannose-type glycans in the envelope gp120. The MVN-resistant virus was still highly sensitive to various other carbohydrate binding lectins (e.g. CV-N, HHA, GNA and UDA), but not anymore to the carbohydrate-specific 2G12 mAb. Importantly, MVN is more than 50-fold less cytotoxic than CV-N. Also in sharp contrast to CV-N, MVN did not increase the level of the activation markers CD25, CD69 and HLA-DR in CD4+ T lymphocytes and subsequently MVN did not enhance viral replication in pre-treated PBMCs. Therefore, MVN may qualify as a useful lectin for potential microbicidal use based on its broad and potent antiviral activity and virtual lack of any stimulatory properties and cellular toxicity.

Anal intercourse remains the most common means of HIV transmission in most of the developed world. Homosexual men represent the largest group of new HIV infections in Australia,[1] Western Europe and North America.[2] The rate of HIV diagnosis in homosexual men is on the increase in these regions,[1-3] and this most likely reflects a true increase in HIV incidence. Recently, it has become clear that homosexual men are also disproportionately affected by HIV in much of the developing world.[2] A detailed understanding of the . .

Antiretroviral treatment inhibits HIV viral replication and reduces plasma viral load. Low plasma viral load is associated with a lower probability of HIV transmission, which opens the possibility of treatment to reduce HIV transmission.[1,2] The feasibility, potential effectiveness, and risks of such treatment are unclear, and a key uncertainty is the extent to which successful antiretroviral treatment reduces HIV infectivity. In the linked observational study (doi:10.1136/bmj.c2205), Del Romero and colleagues estimate the risk of heterosexual transmission of HIV-1 from infected people taking combined antiretroviral treatment.[3]

Only randomised controlled trials comparing transmission in HIV serodiscordant couples, where the infected (index) partner receives or does not receive antiretroviral drugs, can accurately estimate the effect of such treatment on infectivity. The HPTN-052 trial is the only ongoing trial of this type. In this trial, partners infected with HIV are assigned to immediate antiretroviral treatment or deferred treatment when their CD4 count . . .

See relevant article in British Journal of Medicine: "Combined antiretroviral treatment and heterosexual transmission of HIV-1: cross sectional and prospective cohort study"

Background: Vaginal microbicides are topical products being studied for their potential to reduce the risk of penile-vaginal human immunodeficiency virus (HIV) transmission. Because the sexual acts that lead to infection in effectiveness trials are unobserved, identification of an effective vaginal product may be unwittingly circumvented if adherence to product is poor or if participants acquire infection through nonvaginal routes of exposure. Purpose: To model the impact of receptive anal intercourse (RAI) on the measured effectiveness of vaginal microbicides and the power of clinical trials. Methods: A mathematical model is proposed for assessing effectiveness and power as a function of microbicide efficacy, the probability that the microbicide is used for vaginal acts of intercourse with exposure to HIV, the probability that an act of intercourse with exposure to HIV is rectal, and the ratio of transmission probabilities for rectal versus vaginal intercourse. Results: The model demonstrated that a moderate frequency of RAI among vaginal microbicide trial participants is expected to substantially reduce study power; if 1 in 50 acts are rectal, and if the rectal transmission probability is 20-fold greater than that of vaginal intercourse, then power to detect an otherwise 40% effective product with a 160 endpoint trial is reduced from 90% to 56%. If 1 in 25 acts are rectal then power is only 34%. Limitations: Accurate reports of adherence and rates of RAI are difficult to obtain, and precise HIV transmission probabilities are unknown. Hence the true impact of unprotected RAI on vaginal microbicide trials cannot be quantified with certainty. Conclusions: Counseling against RAI should be provided to all vaginal microbicide trial participants irrespective of sexual history. Collection of accurate behavioral data on RAI during trials is essential to understand whether failure to demonstrate an effect might be attributed to RAI.

Background: Anal sex is an important yet little studied HIV risk behavior for women. Methods: Using information collected on recent sexual encounters, we examined the influence of sex partner and relationship characteristics on the likelihood of engaging in anal sex among women with a high risk of HIV infection. Results: Anal sex was nearly 3 times more common among actively bisexual women (OR = 2.96, 95% CI: 2.17-4.03). Women were more likely to have anal sex with partners who injected drugs (OR = 2.32, 95% CI: 1.44-3.75), were not heterosexual (OR = 1.85, 95% CI: 1.18-2.90), and with whom they exchanged money or drugs for sex (OR = 1.79, 95% CI: 1.10-2.90). The likelihood of anal sex also increased with the number of nights sleeping together (OR = 1.15, 95% CI: 1.06-1.24). In contrast, emotional closeness and social closeness were not associated with anal sex. Condom use during anal sex was uncommon, and did not vary according to partner or relationship characteristics. Conclusions: Our findings support the need for HIV prevention interventions that target anal sex among heterosexuals, particularly in drug-using populations residing in neighborhoods with elevated levels of HIV prevalence.

Objective: To identify demographic and behavioral correlates of heterosexual anal intercourse (AI), as well as associations with sexually transmitted infections (STI) among clients attending public sexually transmitted disease (STD) clinics. Methods: We conducted a cross-sectional study of clients attending 13 public STD clinics in Los Angeles County, CA. Data collected included information on demographics, types of sexual contact, substance use, other risk behaviors, and STI results. Results: Overall, 10% of heterosexual men (n = 1,978) and 10% of women (n = 1,364) reported AI with an opposite sex partner in the 90 days preceding their clinic visit. Women who engaged in AI were more likely to report exchange of drugs or money for sex (adjusted odds ratio [AOR] = 2.80; 95% confidence interval [CI]: 1.95-4.02], substance use (AOR = 1.35; 95% CI: 1.17-1.55), and less likely to be African American (AOR = 0.53; 95% CI: 0.43-0.65). Among men, African American men were less likely to report heterosexual AI (AOR = 0.70; 95% CI: 0.60-0.82), while Hispanic men (AOR = 1.50; 95% CI: 1.29-1.76) were more likely to report heterosexual AI when compared to white men. Other factors associated with AI among men included exchange of drugs/money for sex, anonymous sex, and sex with an injection drug user. Among both men and women factors associated with AI varied by race/ethnicity. Conclusions: Recent heterosexual AI was reported by a nontrivial proportion of clients seen at public STD clinics. Those who reported AI were also more likely to report risk behaviors that place them at high-risk for transmitting or acquiring STIs/HIV.

Globally, sexually transmitted infections (STIs) represent a significant source of morbidity and disproportionately impact the health of women and children. The number of randomized controlled trials testing interventions to prevent STIs has dramatically increased over time. To assess their impact, the authors conducted a systematic review of interventions to prevent sexual transmission or acquisition of STIs other than human immunodeficiency virus, published in the English-language, peer-reviewed literature through December 2009. Ninety-three papers reporting data from 74 randomized controlled trials evaluating 75 STI prevention interventions were identified. Eight intervention modalities were used: behavioral interventions (36% of interventions), vaginal microbicides (16%), vaccines (16%), treatment (11%), partner services (9%), physical barriers (5%), male circumcision (5%), and multicomponent (1%). Overall, 59% of interventions demonstrated efficacy in preventing infection with at least 1 STI. Treatment interventions and vaccines for viral STIs showed the most consistently positive effects. Male circumcision protected against viral STIs and possibly trichomoniasis. Almost two-thirds of behavioral interventions were effective, but the magnitude of effects ranged broadly. Partner services yielded similarly mixed results. In contrast, vaginal microbicides and physical barrier methods demonstrated few positive effects. Future STI prevention efforts should focus on enhancing adherence within interventions, integrating new technologies, ensuring sustainable behavior change, and conducting implementation research.

Background A feasibility study was conducted to investigate whether an occupational at-risk cohort of women in Mwanza, Tanzania are a suitable study population for future phase III vaginal microbicide trials. Methodology/Principal Findings 1573 women aged 16-54 y working in traditional and modern bars, restaurants, hotels, guesthouses or as local food-handlers were enrolled at community-based reproductive health clinics, provided specimens for HIV/STI and pregnancy testing, and asked to attend three-monthly clinical follow-up visits for 12-months. HIV positive and negative women were eligible to enter the feasibility study and to receive free reproductive health services at any time. HIV prevalence at baseline was 26.5% (417/1573). HIV incidence among 1156 sero-negative women attending at baseline was 2.9/100PYs. Among 1020 HIV sero-negative, non-pregnant women, HIV incidence was 2.0/100PYs, HSV-2 incidence 12.7/100PYs and pregnancy rate 17.8/100PYs. Retention at three-months was 76.3% (778/1020). Among 771 HIV sero-negative, non-pregnant women attending at three-months, subsequent follow-up at 6, 9 and 12-months was 83.7%, 79.6%, and 72.1% respectively. Older women, those who had not moved home or changed their place of work in the last year, and women working in traditional bars or as local food handlers had the highest re-attendance. Conclusions/Significance Women working in food outlets and recreational facilities in Tanzania and other parts of Africa may be a suitable study population for microbicide and other HIV prevention trials. Effective locally-appropriate strategies to address high pregnancy rates and early losses to follow-up are essential to minimise risk to clinical trials in these settings.

Development of an effective vaccine against HIV-1 will likely require elicitation of broad and potent neutralizing antibodies against the trimeric surface envelope glycoprotein (Env). Monoclonal antibodies (mAbs) PG9 and PG16 neutralize ~80% of HIV-1 isolates across all clades with extraordinary potency and target novel epitopes preferentially expressed on Env trimers. As these neutralization properties are ideal for a vaccine-elicited antibody response to HIV-1, their structural basis was investigated. The crystal structure of the antigen-binding fragment (Fab) of PG16 at 2.5 A resolution revealed its unusually long, 28-residue, complementarity determining region (CDR) H3 forms a unique, stable subdomain that towers above the antibody surface. A 7-residue "specificity loop" on the "hammerhead" subdomain was identified that, when transplanted from PG16 to PG9 and vice versa, accounted for differences in the fine specificity and neutralization of these two mAbs. The PG16 electron density maps also revealed that a CDR H3 tyrosine was sulfated, which was confirmed for both PG9 (doubly) and PG16 (singly) by mass spectral analysis. We further showed that tyrosine sulfation plays a role in binding and neutralization. An N-linked glycan modification is observed in the variable light chain, but not required for antigen recognition. Further, the crystal structure of the PG9 light chain at 3.0 A facilitated homology modeling to support the presence of these unusual features in PG9. Thus, PG9 and PG16 use unique structural features to mediate potent neutralization of HIV-1 that may be of utility in antibody engineering and for high-affinity recognition of a variety of therapeutic targets.

The London School of Hygiene & Tropical Medicine (LSHTM) is delighted to announce that its new Director will be Professor Peter Piot. He will take over the role from Professor Sir Andy Haines in September. Baron Piot is currently Director of the Institute for Global Health and Professor of Global Health at Imperial College London. Following positions at the Institute of Tropical Medicine in Antwerp, the University of Nairobi and WHO, Professor Piot was Executive Director of the Joint United Nations Programme on HIV/AIDS (UNAIDS) and Under Secretary-General of the United Nations between 1995 and 2008. Upon accepting the offer of appointment, Professor Piot noted, "I am delighted and honoured to accept the role of Director of the prime global public health institution in the world. I look forward to bringing my combined background of research, teaching, policy and management to the School, and to working with staff and students to improve health in the UK and globally."

CONRAD is pleased to announce that Executive Director, Henry Gabelnick, Ph.D, was awarded the lifetime achievement award at the 6th International Microbicides 2010 Conference. This year's conference, Building Bridges to HIV Prevention, was held in Pittsburgh, Pennsylvania May 22-25 and before an audience of more than 1,000 HIV advocates and scientists, Dr. Gabelnick was recognized for his unparalleled commitment and dedication to the development of microbicides. The lifetime achievement award was his second -- in 2005, Dr. Gabelnick was recognized by the International Conference on AIDS India for a lifetime devoted to reproductive health. "In a field with so many dedicated, brilliant and persistent researchers, I am tremendously honored to be singled out by my peers," said Dr. Gabelnick. 

President Obama, his foreign policy team, and Congress are on the cusp of redefining how the United States approaches foreign assistance. As they undertake their aid reform effort this year, they're promising to get serious about ensuring that American funds are used wisely. They're right to focus on results. And one of the best ways to guarantee that our aid dollars actually deliver for those in need is to use them to develop innovative new tools for combating the health problems that plague the developing world.

The need for research breakthroughs is as urgent as ever. Almost five million people die each year from HIV/AIDS, tuberculosis, and malaria. Yet vaccines for HIV and malaria do not yet exist and existing tuberculosis vaccines are outdated and ineffective. For many other neglected infectious diseases, effective prevention, diagnostics, and treatments simply do not exist, and many tools that do exist are not effective against some conditions.

The Australian Research Centre in Sex, Health and Society (ARCSHS) at La Trobe University will host a two day workshop which will bring together 20 social researchers from Bangladesh, Cambodia, Indonesia, Thailand, Vietnam, and the Philippines currently working in the area of MSM. The two day workshop will take place in Sydney on October 18 and 19, prior to the Australasian HIV Conference.  The workshop will advance a research agenda for effective work on HIV/AIDS with men who have sex with men. The workshop will be structured in two parts: 1) the establishment of strategic social research priorities with MSM populations, and 2) the development of concrete research proposals in at least two identified areas. If you are a researcher currently work in the area of MSM and HIV and would like to attend this meeting please contact Dr Stephen McNally at the Australian Research Centre in Sex, Health and Society, La Trobe University s.mcnally@latrobe.edu.au.

AVAC and various partner organizations recently released new reports on the state of the prevention research field:

The Thai Way Forward, a preview of the AVAC Report 2010 Turning the Page, looks at some of the questions and reactions that the landmark Thai vaccine study raised for the Thai participants, scientists and advocates. The full AVAC Report will be released in July.

The International Rectal Microbicide Advocates (IRMA) released From Promise to Product: Advancing Rectal Microbicide Research and Advocacy, which provides an overview of the maturing rectal microbicide research field, resource mapping, and global advocacy goals. The report is available in English and Spanish on the IRMA website along with useful fact sheets, adaptable PowerPoint presentations and more.

Microbicides: Ways Forward is the final in a series of strategy documents put out by the Alliance for Microbicide Development. In 2009, the Alliance surveyed a number of microbicides experts and key stakeholders in the field in an effort to identify areas of progress, obstacles that remain and priorities for the field. These conversations and insights inform much of the new report, which concludes with nine key recommendations for moving the microbicide field forward. The Alliance officially closed at the end of 2009, and this report is one of many key Alliance resources that are being integrated into AVAC's continually expanding education, outreach, advocacy and policy work. Visit www.avac.org/orderpublications to request a printed copy.

The Communications Handbook for Clinical Trials is a practical guide developed for site-level researchers, communicators, advocates and others working on HIV prevention trials in developing countries. It provides guidance on how to anticipate and respond to the special communications challenges posed by the conduct of clinical research. Organized to correspond to the chronological steps involved in conducting research, it focuses on the various communications skills that are needed throughout the course of a trial. A collaborative project, the Handbook includes context-specific case studies and practical insights from actual clinical trial communications initiatives. The Handbook was co-published by the Microbicide Media and Communications Initiative (MMCI) and Family Health International (FHI). Email handbook@mmci-communications.org to order your free hard copy and the 30-minute DVD that accompanies the Handbook.