28 MAY 2010, VOLUME 11, ISSUE 18

The 2010 International Microbicides Conference (M2010) ran from May 22-25 in Pittsburgh, in the US. The theme was "Building Bridges in HIV Prevention".

The HIV Prevention and Control Bill was yesterday presented to Parliament with measures to curb the spread of the disease. It was drafted by the parliamentary committee on HIV/AIDS and tabled by MP Beatrice Rwakimari. During consultative meetings on the draft, several individuals and civil society organisations protested some of the clauses and demanded that they be deleted. Human rights activists argued that the clause would increase discrimination against people living with HIV and dampen the efforts Uganda has taken to fight the scourge. However, the Bill also fights discrimination, against both the employed and students.

See related articles: Don't pass HIV/AIDS Bill in a hurry andUganda: protect, don't punish, people with HIV

Anyone who is going to take antiretroviral drugs for prevention -- either orally or through a microbicide -- must know his or her HIV status to avoid drug resistance developing, Dr John Mellors from the University of Pittsburgh said at the M2010 Microbicides conference today. "If someone is infected and takes PrEP (pre-exposure prophylaxis) this would be really bad," he said, explaining how that person would promote the spread of resistant HIV strains.

An expert on resistance, Mellors said some drug resistance among people taking antiretroviral therapy was inevitable. About 80% of people currently on treatment have suppressed their virus. Most (4/5) of the 20% who have not, have some resistant virus. Mellors expressed concern at the "substantial overlap in the drugs being used for treatment and those being studied for prevention". He said in a worst case scenario widespread resistance at a population level to these drugs could end up rendering them ineffective for both treatment and prevention.

It is well understood that both the efficacy and effectiveness of HIV Prevention research trial products (such as microbicides) depends upon their actual use by the clinical trial participants. "Use is a function of human behaviour and action that is affected by an individual, interpersonal, social, and cultural factors that operate interactively in complex, dynamic and varied ways across settings" said Dr Judith D Auerbach, Vice President for Science and Public Policy at the San Francisco AIDS Foundation, USA. Dr Judith D Auerbach was speaking at the International Microbicides Conference (M2010) in Pittsburgh, USA (23-25 May 2010).

In HIV prevention research, it is the job of social and behavioural scientists sometimes in collaboration with biomedical scientists to unpack these complex, dynamic and interactive factors and the effect they had on promising biomedical tools. Historically social and behavioural research has been conducted at the level of being adjunct or handmaiden in HIV prevention trials. "Its purpose is to elucidate the likelihood that clinical trial population in the first place and larger population in the second case, will take up a particular prevention tool as prescribed, to help assess the safety and efficacy of that particular prevention tool" said Judith. In recent years there are a number of thoughtful articles written on the need on how best to integrate social research into the microbicides clinical trials from pre-clinical to safety and efficacy studies of vaginal and rectal products.

The use of lubricants during unprotected anal intercourse may indirectly raise the risk of HIV transmission in the receptive partner, among both men and women, new research warns. Concern about the possibility is being raised in the form of two new studies, and revolves around the fact that HIV infection risk rises if other infections are already present in the rectal lining of the receptive partner, the study authors noted. In that light, indications that some lubricants may contribute to a generally increased risk for sexually transmitted infections, and therefore in turn for HIV, are scheduled for presentation this week in Pittsburgh at the International Microbicides Conference.

Conducted between 2006 and 2008, one study -- which focused on approximately 900 residents in the Baltimore and Los Angeles region -- observed that men and women who use lubricants in general are three times more likely to have some form of a rectal sexually transmitted infection. The finding held regardless of gender, HIV status, condom use, and the number of sex partners the study participants had had in the prior month. Although no specific lubricants were identified as particularly problematic, most study participants said they used a water-based lubricant (76 percent), while 28 percent used silicon-based products, 17 percent oil-based lubricants, and 6 percent said used a numbing lubricant.

The second study -- led by Charlene Dezzutti of the University of Pittsburgh and the Microbicide Trials Network -- looked at five of the most popular over-the-counter and/or mail-order lubricants, identified as such through a survey of 9,000 men and women living in 100 different countries. All the lubricants were water-based, except for one silicon-based product.

Surveys of condom use in women based on self-report may be seriously unreliable, to the extent of overestimating true use by 100%, the Microbicides 2010 Conference heard yesterday. This finding comes from a South African survey but if it applies broadly it may have significant effects on trial design and mathematical modelling of the effect of microbicides. Mitzi Gafos of the Africa Centre for Health and Population Studies (ACHPS) discussed results from a longitudinal survey of 1177 women at the ACHPS, a rural centre north of Durban. The study was part of the MDP301 trial of the PRO2000 microbicide, which failed to demonstrate efficacy last year.

Local HIV prevalence is extremely high at 22%, peaking at over 50% in women aged 25 to 29. South African surveys of condom use report that there has been a considerable increase in condom use in the last decade, with the proportion of women reporting condom use at last sex increasing from 27% in 2002 to 68% in 2008. ACHPS reported similar figures in its year-long study, with an increase of condom use at last sex from 58% to 68% over the year. However these reported increases in condom use have not been accompanied by any decline in HIV incidence, except possibly in teenagers, though the methodology of the national survey that found evidence for this decline has been criticised. HIV incidence in women attending ACHPS has stayed at 4.4% a year, with no decline at all since 2003.

The number of women infected with HIV has risen worldwide. In the hardest hit region, Sub-Saharan Africa, six out of ten adults living with the virus are women. Researchers are gathering in Pittsburgh this week to discuss novel methods of preventing women from becoming infected. The products are called microbicides. South Africa has more people living with HIV than any other country. Researchers say women who live in rural areas are especially vulnerable. Dr. Samukeliso Dube is the African program director with the Global Campaign For Microbicides. "The expectation is that they are a conduit for bearing children, and they are a conduit for sexual pleasure for men," Dr. Dube says. "And in these cultural setups, it's actually a taboo for them to ask their partners to wear a condom."

Africa needs microbicides for both vaginal and rectal use in prevention of mucosal infection of HIV, a mini-symposium at the ongoing International Microbicides Conference in Pittsburgh, Pennsylvania, US was told. The symposium heard that the contribution to HIV flame in Africa by the anal route is still under-reported and that time to unpack the myth was long overdue.

According to Dr Salim S. Abdool Karim, Pro Vice-Chancellor (Research), Univesity of KwaZulu Natal and Director of the Center for the AIDS Programme of Research in South Africa, CAPRISA, Africa needs to take a leap from the assumptions that HIV is spread only through the penile route. "But a rectal microbicide as a new HIV prevention technology is urgently needed in Africa for the large number of people practicing anal sex -- namely the men who have sex with men, bisexual men and women", he said.

Dr Karim said although data on anal sex is as rare as data on the true situation of HIV in men who have sex with men throughout Africa, anonymous surveys in various parts of Africa show interesting pictures. In Cape Town, South Africa, a survey of 2593 men and 1818 women showed that 14% of men and 10% of women had anal intercourse in the past three months. In KwaZulu Natal, South Africa, 40.8% of the surveyed reported practicing anal intercourse. Worse, 30% of these reported never or rarely using condom during an intercourse. Dr Karim said consistent use of condom in anal sex was lower that peno-vaginal intercourse.

Two surveys of men who have sex with men (MSM) in Nigeria who are attending local HIV support organisations show that between a third and half of men who are attracted to other men define as bisexual and as many have had vaginal sex with a women as anal sex with a man. The 'snapshot' survey adds another country to the list of African countries that have documented a hitherto invisible MSM culture -- see recent report -- and adds to evidence presented elsewhere at the 2010 International Microbicides Conference that even in supposedly heterosexually-driven epidemics, anal sex may play a much larger role than previously thought. It also found high rates of anal sex between men and women. However, only 10% of MSM were consistent condom users and only 3% had used any form of water-based lubricant or understood what a lubricant was. Education sessions discussing microbicides had found that 68 to 74% of MM would be willing to use a rectal microbicide.

Their scientific methods may have been quite different, but their conclusions were not. In asking whether drug resistance could be a problem if antiretroviral (ARV) drugs become a mainstay for HIV prevention, the two studies - one involving a mathematical model and the other assays of cells and tissue - arrived at the same answer. Resistance could happen if people who are unknowingly already infected use the approach. The results of these studies, which were reported today at the International Microbicides Conference (M2010) in Pittsburgh, USA, underscore the importance of incorporating routine HIV testing and ongoing monitoring of infection status in any prevention program that involves the use of ARVs.

See related press release: Using ARVs to prevent HIV could result in drug resistance if routine screening is not done

Tablets, insertable rings and dissolving films can effectively deliver drugs to help protect women and perhaps men from infection with the AIDS virus, researchers reported on Monday. They also found evidence that using such an approach -- called a microbicide -- may help overcome some of the risks of drug resistance that can come with taking pills to prevent infection.

Here are some of the findings from the International Microbicides Conference being held in Pittsburgh:

• A flexible ring designed for use in the vagina can continually deliver two AIDS drugs for up to a month. Andrew Loxley of Bethlehem, Pennsylvania-based Particle Sciences, Inc., and colleagues lab tested a vaginal ring that time-released dapivirine, a drug made by Johnson & Johnson's Tibotec Inc and licensed to the International Partnership for Microbicides, and the entry inhibitor maraviroc sold by Pfizer under the brand name Selzentry. It has not been tested in people yet.
• A vaginal tablet worked in similar fashion, time-releasing maraviroc and another experimental HIV drug called DS003, licensed to the International Partnership for Microbicides by Bristol-Myers Squibb, Sanjay Garg of the University of Auckland in New Zealand told the conference. The tablet uses a polymer designed to attach to the moist lining inside the vagina.
• A third approach uses a film, Anthony Ham of ImQuest BioSciences of Frederick, Maryland reported. ImQuest is testing the HIV drug IQP-0528 in a film smaller and thinner than a stick of gum, similar to a mouthwash strip.

The development of new microbicides to protect against HIV infection is progressing steadily with promising options in the pipeline, researchers reported today at the M2010 Microbicides conference in Pittsburgh, in the US. Microbicides are substances, like gels or creams, designed to stop HIV or other sexually-transmitted infections when applied topically inside the vagina or rectum. Advances in this field since the last conference in India two years ago include: the completion of a human clinical trial testing the first microbicide using an antiretroviral agent (tenofovir) in South Africa, with the results to be released in July; the testing of products combining two antiretroviral drugs in the laboratory; new classes of antiretroviral drugs being tested in the lab and animals; and new ways of delivering the drug into the vagina including a flexible ring, tablet or thin film.

"We have moved beyond gels in a big and meaningful way," said Dr Joseph Romano from the International Partnership for Microbicides. "This is a big, big difference from a few years ago when we were focused primarily on gels.

The microbicides field has undoubtedly moved and shifted a lot in the past decade. Now, with first generation microbicides candidate products up and gone, antiretroviral treatment (ART)-drug based microbicides in spotlight, and only three major microbicides efficacy studies remaining, the need to lobby for increased funding of microbicides research and development, was never so compelling.

The need to bolster HIV prevention has certainly not dimmed - and so has the need to up HIV treatment, care and support which is becoming acute on daily basis. The International Microbicides Conference (M2010) opened with the plenary that cited UNAIDS data, from a news from New York Times (At Front Lines, AIDS War Is Falling Apart) "For every 100 people put on antiretroviral treatment (ART), 250 people are getting newly infected with HIV."

"People were already questioning that whether universal access to treatment is achievable without significantly reducing the number of new infections" said Professor (Dr) Robin Shattock, who is a Professor of Cellular and Molecular Infection in the Department of Cellular and Molecular Medicine at St George's University of London, UK.

Men in a relationship with an HIV-positive woman face double the risk of becoming infected themselves when their partner is pregnant, new research reveals. The finding is slated for presentation Sunday at the International Microbicides Conference in Pittsburgh.

The two-year study -- launched in Botswana, Kenya, Rwanda, South Africa, Tanzania, Uganda and Zambia -- focused on more than 3,300 couples in which one of the partners was HIV-positive. Dr. Nelly Mugo, from the University of Nairobi and Kenyatta National Hospital in Nairobi, and colleagues teamed with investigators from the University of Washington in Seattle to track 1,085 couples in which the man was HIV-positive, and 2,236 couples in which the woman was infected.

During the duration of the study, 823 pregnancies occurred. The study authors found that pregnancy increased HIV transmission in both directions: male-to-female and female-to-male. However, the observed infection risk for women appeared to be a function of several factors beyond pregnancy itself, including sexual behavior. For men, the link between pregnancy and risk increase was much stronger and more direct, Mugo's team noted. Factors such as the viral load and CD4 count (an indicator of immune system strength) of the infected female partner had no impact on the man's risk. Nor did the man's circumcision status or whether or not the couple had engaged in unprotected sex, the researchers found.

The research team therefore theorized that the doubling of female-to-male transmission risk during pregnancy might be attributed to both immunological and physiological changes -- as yet unidentified -- that are triggered by pregnancy. But they cautioned that more research will be needed to explore this possible explanation.

A number of presentations at the Microbicides 2010 Conference in Pittsburgh concerned microbicide research using established classes of HIV drugs that have not been used as microbicides before. Trial of microbicides and pre-exposure prophylaxis (PrEP) in humans have so far only involved two classes of drugs: the nucleoside reverse transcriptase inhibitors (NRTIs) tenofovir and FTC in large randomised controlled trials, and the non-nucleoside reverse transcriptase inhibitors (NNRTIs) dapivirine and UC781 in phase 1 safety trials.

If people taking PrEP are nonetheless infected with HIV, or are doing so with an undiagnosed infection, there is a significant possibility of the development of HIV drug resistance, and there is a theoretical risk of resistance in microbicides too. There is therefore an urgent need to research other drugs as microbicides and PrEP agents both to minimise the risk of prevention and to provide 'second line prevention' should HIV drug resistance become prevalent.

There are many experimental classes of drug being tested for use as microbicides, but using ones with a history as HIV treatments removes some of the need to demonstrate safety and shortens the preclinical and phase 1 phases of development: leading researcher Robin Shattock told the conference that the failure of microbicide-specific classes to show efficacy has injected new urgency into the need to demonstrate proof of concept (see separate story). Two new classes of drug -- an integrase inhibitor and the CCR5 inhibitor maraviroc -- are amongst drugs that have now been used to prevent HIV infection in monkeys, and await funding to go into human trials.

Professor Robin Shattock, director of the microbicide research programme at St George's Hospital in London, warned delegates in an opening plenary at the Microbicides 2010 Conference in Pittsburgh yesterday that "we stand at a critical timepoint in microbicide development". "There is a recognised need to prioritise and accelerate efficacy testing in clinical trials," he said, before funders lost interest in the approach.

The failure of the first-generation of non-ARV-based candidates had left only three efficacy microbicide studies in humans ongoing or planned, he pointed out. The first is CAPRISA in South Africa, a phase 2b trial of tenofovir gel which will present its findings at the Vienna International AIDS Conference in July 2010. VOICE, a phase 3 trial testing tenofovir gel and tenofovir and tenofovir/FTC PrEP, is recruiting now and will report in 2011. The long-awaited IPM009 trial of dapivirine in a vaginal ring and/or gel is not due to start till 2012.

From having been a favoured option as new prevention technologies, microbicides were now second to pre-exposure prophylaxis in terms of the number of efficacy trials ongoing or planned, though some trials such as VOICE are studying both concepts.

Researchers say a vaginal gel could protect from HIV, based on preliminary findings in monkeys that obtained protection from a virus similar to HIV. The study is the first experiment using an antimicrobial gel with an integrase inhibitor that is currently used to prevent HIV from replicating and taken orally by HIV infected patients. The use of a vaginal gel composed of the antiviral compound L-870812 was found to protect female pigtailed macaques from SIHV, a combination of HIV and a virus found in monkeys. Three monkeys were used, and one for control given a placebo.

The vaginal gel was applied twice a week for seven weeks. Thirty minutes after the gel was applied researchers exposed the monkeys to the human equivalent of HIV, finding that the gel worked to protect from SHIV up to seven weeks. One of the monkeys receiving the vaginal gel was found to have the SHIV virus after seven exposures, but encouragingly, showed no signs of drug resistant virus and continued using the gel for fifteen weeks. Those findings are important because of past concerns that patients can develop drug resistant HIV from using antiviral medications. The control monkey developed SHIV after three challenges.

As the world waits to see whether the tenofovir microbicide tested in South Africa will block HIV infection -- the results will be released in July -- marketing expert Paul McGowan from the agency Added Value spoke about the role that marketing could play in promoting any successful product. He said that HIV prevention messages were struggling to get through in South Africa since people had reached "saturation point" on HIV.  McGowan said a survey of modern young women found they were not receptive to prevention messages and felt like they were not at risk of the virus -- in a country where an estimated 10% of the adult population is HIV positive. "They had the idea it won't happen to me, they feel safe, the only sleep with nice people ... it is still his decision and to challenge him is to risk the relationship, they don't talk about HIV and feel it is better not to know than to shatter a dream," said McGowan. He said it would be necessary to create a desire for microbicides -- to turn them into a product that people cannot live without.

New HIV infections in South Africa could be almost eliminated by combining prevention tools that have been proven to reduce transmission, an expert on the virus told a conference in the US yesterday.

Dr Susan Buchbinder said scientific trials had shown that medical male circumcision, condoms and the prevention-of-mother-to-child therapies lowered the risk of infection. In South Africa an estimated 1600 people a day are infected with HIV. But microbicides have not yet been shown to block the virus. For this reason, the 1000 delegates at the M2010 Microbicides conference in Pittsburgh, US, are eagerly waiting for the results -- to be released in July -- of the first human clinical trial to test an antiretroviral drug-based microbicide. The microbicide has been tested in a study led by University of KwaZulu-Natal Professor Salim Abdool Karim. Another prevention strategy being tested in South Africa is PrEP (pre-exposure prophylaxis), in which HIV-negative people take antiretrovirals to stop infection.

Mitchell Warren, executive director of global advocacy organisation AVAC, said: "Not only is South Africa at the forefront of testing individual approaches but it is leading the development of combination prevention, which is clearly the only way to truly end the epidemic." Three microbicide and PrEP trials are under way at sites across South Africa, another is taking place among couples in which one partner is positive and the other negative, and the country has been involved in vaccine trials.

If someone like 23-year-old Erik H. had walked through the doors of the National Institutes of Health (NIH) Clinical Center in the 1980s and asked how long he had to live, the answer would have been grim. We'd have told the recent college graduate that he probably had less than a year.

Today, the future is far brighter for Erik and millions of others infected with the human immunodeficiency virus, or HIV--the retrovirus that causes acquired immunodeficiency syndrome, or AIDS. Because of the development of truly transformative drugs by researchers in government, at universities and hospitals, and in the biotech and pharmaceutical industries, HIV-positive people can now look forward to decades of life. Someone like Erik can expect to survive until age 70 or even beyond.

In 2009, Erik became extremely ill with severe weight loss and chronic diarrhea. After tests revealed that the Maryland resident was HIV-positive, a hospital social worker steered him into NIH's Partnership for Access to Clinical Trials (PACT) program, which brings together community-based health-care providers, patients, and NIH research clinicians.

Judge sentences Tiwonge Chimbalanga and Steven Monjeza to maximum prison term for sodomy and indecency

The worst fears of a gay couple in Malawi and supporters across the world were realised today when they were sentenced to 14 years in jail with hard labour. Steven Monjeza, 26, and 20-year-old Tiwonge Chimbalanga, convicted earlier this week of unnatural acts and gross indecency, now face "hell on earth" in the maximum security Chichiri prison in Blantyre, where they have been held on remand. The sentence, the harshest possible that the judge could have handed down, provoked outrage from human rights activists in the southern African country, where homosexual acts are illegal, and from the international community.

To the Editor:

Re "In South Africa, an Unlikely Leader on AIDS" (front page, May 15):
That government and tribal leaders acknowledge the reality of H.I.V. and AIDS and endorse safe-sex practices is crucial in diminishing the spread of and stigma associated with H.I.V. and AIDS in South Africa. With luck, their actions will inspire their countrymen to do the same. Some here in the United States are disproportionately at a higher risk of being infected with H.I.V. than others. We need to do more to reduce our ignorance and fear of those with H.I.V. or AIDS. Decreasing the rate by which many of our fellow Americans are being infected with the H.I.V. virus should be one of our public health priorities.

The World Health Assembly, the annual gathering of health ministers in Geneva, Switzerland, served as a backdrop on Monday for the launch of a new idea to stimulate research and development on diseases that affect mostly poor countries. The so-called PDP+ Fund, proposed by the International Aids Vaccine Initiative (IAVI); the George Institute for International Health in Sydney, Australia; and pharma giant Novartis, would collect money from governments, Western consumers, and other sources and distribute it among so-called Product Development Partnerships (PDPs). Such partnerships -- including IAVI, the Medicines for Malaria Venture, and the Aeras Global TB Vaccine Foundation -- have proliferated in recent years; they combine the efforts of scientists, donors, and companies to develop products that would not otherwise make it to the market.

Why a new fund in the already crowded global health field? ScienceInsider talked to Mary Moran, director of the George Institute's Health Policy Division and an expert on R&D funding for neglected diseases. (In her definition, that includes the "big three" -- AIDS, malaria, and TB -- and a range of other diseases occurring mostly or only in the developing world.) Moran is the main author of G-FINDER, an annual survey funded by the Bill and Melinda Gates Foundation that tracks global expenditure on R&D for neglected diseases. She was also a member of the Expert Working Group (EWG) at the World Health Organization (WHO) that recently issued a series of recommendations on how to improve R&D funding for these diseases.

In line with its new thinking in bilateral relations with Nigeria, the United States government said yesterday it was embarking on a joint HIV/AIDS vaccine research effort. Speaking while inspecting a medical centre at the Mogadishu Cantonment in Abuja, the US Deputy Secretary of State, Jacob Lew, said the two countries would collaborate with other researchers across the world in a bid to halt the high prevalence rate of the pandemic which presently afflicts 360,000 civilians and about 11,000 military personnel in Nigeria. He said the two countries were in the process of fostering what he described as "smart planning and smart thinking" in its reinvigorated bi-lateral relations.

A fully synthesized genome transforms one species of bacterium into another.

Scientists have built a bacterial genome from scratch and used it to 'reboot' a cell from a different species of bacterium. Daniel Gibson and his colleagues at the J. Craig Venter Institute in Rockville, Maryland, synthesized the genome of the bacterium Mycoplasma mycoides, consisting of about 1.1 million base pairs. Having assembled the genome inside a yeast cell, they transplanted it into a cell from a closely related species, Mycoplasma capricolum. After the newly made cell had divided, the cells of the bacterial colony that it formed contained only proteins characteristic of M. mycoides.

The success clears the way for developing and testing new variants of existing organisms. "With this approach we now have the ability to start with a DNA sequence and design organisms exactly like we want," says Gibson. "We can get down to the very nucleotide level and make any changes we want to a genome." Scientists have already developed many good ways of engineering genes, he adds, but this technique provides an unprecedented ability to make many changes to a genome at once, and to add segments of DNA that aren't found in nature but might be designed to perform useful functions.

To read the study in Science, click here. Also see related articles in Nature: "Synthetic genome resets biotech goals" and "Life after the synthetic cell"

Objectives The sexual behaviour of men who have sex with men (MSM) in southern Africa has been little studied. We present here the first data on bisexual partnerships and bisexual concurrency among MSM in Malawi, Namibia and Botswana. Methods A cross-sectional probe of a convenience sample of 537 men who have ever reported anal sex with another man using a structured survey instrument and rapid-kit HIV screening. Results 34.1% of MSM were married or had a stable female partner, and 53.7% reported both male and female sexual partners in the past 6 months. Bisexual concurrency was common, with 16.6% of MSM having concurrent relationships with both a man and a woman. In bivariate analyses, any bisexual partnerships were associated with lower education (OR 1.6, 95% CI 1.1 to 2.3), higher condom use (OR 6.6, 95% CI 3.2 to 13.9), less likelihood of having ever tested for HIV (OR 1.6, 95% CI 1.1 to 2.3), less likelihood of having disclosed sexual orientation to family (OR 0.47, 95% CI 0.32 to 0.67) and being more likely to have received money for casual sex (OR 1.9, 95% CI 1.3 to 2.7). Bisexual concurrency was associated with a higher self-reported condom use (OR 1.7, 95% CI 1.0 to 3.1), being employed (OR 1.8, 95% CI 1.2 to 2.9), lower likelihood of disclosure of sexual orientation to family (OR 0.37, 95% CI 0.22 to 0.65) and having paid for sex with men (OR 2.0, 95% CI 1.2 to 3.2). Conclusions The majority of MSM in this study report some bisexual partnerships in the previous 6 months. Concurrency with sexual partners of both genders is common. Encouragingly, men reporting any concurrent bisexual activity were more likely to report condom use with sexual partners, and these men were not more likely to have HIV infection than men reporting only male partners. HIV-prevention programmes focussing on decreasing concurrent sexual partners in the African context should also target bisexual concurrency among MSM. Decriminalisation of same-sex practices will potentiate evidence-based HIV-prevention programmes targeting MSM.

Objectives: To describe demographic and behavioral characteristics and the prevalence of HIV and herpes simplex virus type 2 (HSV-2) infections in men who had sex with men identified through a nationally representative, population-based survey. Methods: As part of National Health and Nutrition Examination Surveys in 2001-2006, men 18 to 59 years of age were interviewed about sexual behavior using audio computer assisted self-interview and were tested for antibodies to HIV and HSV-2. Results: Of the 4319 men interviewed, 5.2% reported having ever had sex with men (MSM). MSM were more likely than non-MSM (those reporting female partners only) to have first sex at <15 years (31.9% vs. 17.3%), have >=10 lifetime sex partners (73.6% vs. 40.8%), and have ever used cocaine (46.1% vs. 26.6%) (all P < 0.004). Among MSM, the prevalence of HIV and HSV-2 was 9.1% and 18.4%, respectively. Only 44.5% of MSM reported their sexual orientation as homosexual or gay. Comparing with bisexual and heterosexual MSM, homosexual MSM reported the highest number of lifetime male partners and had the highest HIV prevalence (16.5%). Conclusions: In this population-based sample of men in the United States, self-reported same-sex behavior and homosexual orientation are strong markers for high risk of HIV infection.

Female sex workers (n = 140) were enrolled in a 6-month acceptability trial of the diaphragm. We randomized a subset (n = 40) to receive colposcopies after 1 month of diaphragm use or after 1 month of observation before commencing diaphragm use. Adverse events were mild in nature. Frequency of colposcopic findings did not differ between women randomized to immediate versus delayed diaphragm use (P = 0.25).

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.

The lectin actinohivin (AH) is a monomeric carbohydrate-binding agent (CBA) with three carbohydrate-binding sites. AH strongly interacts with gp120 derived from different X4 and R5 HIV strains, with SIV gp130 and with HIV-1 gp41 at affinity constants (KD) in the lower nM range. The gp120 and gp41 binding of AH is selectively reversed by (a[alpha]1,2-mannose)3 oligosaccharide but not by a1,3/a1,6-mannose- or GlcNAc-based oligosaccharides. AH binding to gp120 prevents binding of the a1,2-mannose-specific monoclonal antibody 2G12, and AH covers a broader epitope on gp120 than 2G12. Prolonged exposure of HIV-1-infected CEM T-cell cultures with escalating AH concentrations selects for mutant virus strains containing N-glycosylation site deletions (predominantly affecting high-mannose type glycans) in gp120. In contrast to 2G12, AH has a high genetic barrier, since several concomitant N-glycosylation site deletions in gp120 are required to afford significant phenotypic drug resistance. AH is endowed with a broadly neutralizing nanomolar activity against laboratory-adapted HIV strains and a variety of X4 and/or R5 HIV-1 clinical clade isolates and blocks viral entry within a narrow concentration window of variation ( 5-fold). In contrast, the neutralizing activity of 2G12 varied up to 1,000-fold depending on the virus strain. Since AH efficiently prevents syncytia formation in co-cultures of HuT-78/HIV-1 and uninfected CD4+ T-lymphocytes, inhibits DC-SIGN-mediated capture of HIV-1 and subsequent virus transmission to CD4+ T-lymphocytes, does not upregulate cellular activation markers, lacks mitogenic activity and does not induce cytokine/chemokines in peripheral blood mononuclear cell cultures, it should be considered as a potential candidate drug for microbicidal use.

Background High plasma HIV-1 RNA concentrations are associated with increased risk of HIV-1 transmission. Initiation of antiretroviral therapy (ART) reduces plasma HIV-1 concentrations. We aimed to assess the effect of ART use by patients infected with HIV-1 on risk of transmission to their uninfected partners. Methods Participants in our prospective cohort analysis were from a randomised placebo-controlled trial that enrolled heterosexual African adults who were seropositive for both HIV-1 and herpes simplex virus type 2, and their HIV-1 seronegative partners. At enrolment, HIV-1 infected participants had CD4 counts of 250 cells per mL or greater and did not meet national guidelines for ART initiation; during 24 months of follow-up, CD4 counts were measured every 6 months and ART was initiated in accordance with national guidelines. Uninfected partners were tested for HIV-1 every 3 months. The primary outcome was genetically-linked HIV-1 transmission within the study partnership. We assessed rates of HIV-1 transmission by ART status of infected participants. Findings 3381 couples were eligible for analysis. 349 (10%) participants with HIV-1 initiated ART during the study, at a median CD4 cell count of 198 (IQR 161-265) cells per mL. Only one of 103 genetically-linked HIV-1 transmissions was from an infected participant who had started ART, corresponding to transmission rates of 0.37 (95% CI 0.09-2.04) per 100 person-years in those who had initiated treatment and 2.24 (1.84-2.72) per 100 person-years in those who had not -- a 92% reduction (adjusted incidence rate ratio 0.08, 95% CI 0.00-0.57, p=0.004). In participants not on ART, the highest HIV-1 transmission rate (8.79 per 100 person-years) was from those with CD4 cell counts lower than 200 cells per mL. In couples in whom the untreated HIV-1 infected partner had a CD4 cell count greater than 200 cells per mL, 66 (70%) of 94 transmissions occurred when plasma HIV-1 concentrations exceeded 50 000 copies per mL. Interpretation Low CD4 cell counts and high plasma HIV-1 concentrations might guide use of ART to achieve an HIV-1 prevention benefit. Provision of ART to HIV-1 infected patients could be an effective strategy to achieve population-level reductions in HIV-1 transmission.

See related comment on this article in the Lancet: "HIV drugs for treatment, and for prevention" 

A community educator who developed innovative ways to link women in Tanzanian villages with life-saving HIV prevention information and with HIV prevention research trials has received the second Omololu Falobi Award for Excellence in HIV Prevention Research Community Advocacy. The award was presented during the closing ceremony of the Microbicides 2010 Conference in Pittsburgh, USA.

Charles Shagi, a Program Officer for the African Medical and Research Foundation based in Mwanza, Tanzania, was honored for his significant contributions to developing and sustaining community engagement and education programs that empower women and their communities to advocate for themselves and to become vital partners in HIV prevention research trials.

"Bringing HIV prevention research to communities is an essential part of our work to develop new HIV prevention options for men and women," said Sharon Hillier, Microbicides 2010 Co-chair and a member of the award selection committee. "Charles embodies what this award was created to recognize: leadership, commitment and passion in community advocacy. He works tirelessly not only to help women advocate on their own behalf and to become involved in research, but also to educate and empower researchers to understand the needs of women, their families and communities."

"I am very humbled to accept this award, and for me, it really underscores the value this field put on the importance of reaching out to the women -- in the villages of Tanzania and around the world -- who participate in these trials," said Shagi. "This award is important because it proves that people do care about them. It is the courage of those women that is being honored today. I look forward to continuing to share the voices and experiences of vulnerable women with the research and advocacy communities."

Purpose: Support a limited number of awards using combined family planning and microbicides funding to address a focused set of family planning/reproductive health (FP/RH) issues.  Funds may support the R&D, regulatory approval, and introduction of new contraceptives that fill existing gaps in the FP method mix, and multipurpose prevention technologies (MPTs) that meet various RH needs of women in low resource settings.  The innovative and potentially varied nature of these activities and products, which are united by a theme but not necessarily a common technological platform or programmatic focus, may require a diversity of partners with differing areas of expertise.  Thus, the intention of the APS is to marshal the greatest amount of technical expertise for promising product leads and initiatives, while remaining flexible enough to support innovation and respond to the most pressing needs of the field.

Objective: Foster the R&D, regulatory approval, and introduction of:

1. New contraceptive methods that fill specific gaps in the existing method mix, and are appropriate for low-resource settings;
2. MPTs that are contraceptive and provide protection from HIV, other sexually transmitted infections (STIs), and/or reproductive tract infections (RTIs); are appropriate for occasional or intermittent use; and/or provide additional health benefits.

All of the relevant information, including the rapid response timeline, can be viewed on http://www.grants.gov/, funding opportunity # APS-OAA-10-000003.

A special section of Public Health Reports (PHR) (March-April 2010) was produced that contains six articles that provide a synopsis of research conducted under the Horizons program from 1997 to 2008. We hope that in providing this backward-looking but forward-thinking review of work accomplished under the Horizons program, other organizations may find the results useful for their own program planning and implementation. Click here to find links to the abstracts for the articles as well as links to the PDFs of the background papers from which these journal articles were written.

Looking Back, Moving Forward:

• Access to Antiretroviral Therapy for Adults and Children with HIV Infection in Developing Countries: Horizons Studies, 2002 to 2008
• Implementing PMTCT Programs in Resource-constrained Settings, Horizons studies 1999 to 2007
• Improving the Lives of Orphans and Other Children Affected by AIDS, Horizons Studies 1998 to 2007
• Promoting Gender Equity to Fight HIV, Horizons Studies 1999 to 2007
• Reducing HIV-related Stigma, Horizons Studies 2000 to 2007
• Understanding the HIV Risk and Sexual Health Needs of Men Who Have Sex with Men: Horizons Studies 2001 to 2008

Request for Applications (RFA) Number: RFA-AI-10-022
Letters of Intent Receipt Date(s): July 2, 2010
Application Due Date(s): August 3, 2010
Purpose.  This Funding Opportunity Announcement (FOA) solicits Exploratory/Developmental (R21) applications from United States (U.S.)-funded institutions with an Indian-institution partner to establish Collaborative Research Partnerships (CRP) in the field of HIV/AIDS prevention or in preventing, treating, or ameliorating HIV-related co-morbidities such as malignancies, metabolic complications or opportunistic infections (OIs). The U.S.-India Bilateral CRP Program is designed to develop collaborations between scientists and institutions in the U.S. and India to conduct high quality HIV/AIDS prevention research of mutual interest and benefit to both countries while developing the basis for future institutional and individual scientific collaborations. This FOA will utilize the research capacities of the institutions and scientists in both countries to advance the field of HIV/AIDS prevention and to develop preliminary data that may support a more extensive future research proposal to test an HIV/AIDS prevention program.
Mechanism of Support. This FOA will utilize the R21 award mechanism.
Funds Available and Anticipated Number of Awards. It is anticipated that $3 million will be available in FY 2011 to fund 8 to 10 new awards. The Indian Council for Medical Research (ICMR) and/or other Indian Government research funding organization plans to issue a similar call for applications to support the Indian collaborators. Awards issued under this FOA are contingent upon the availability of funds and the submission of a sufficient number of meritorious applications.
Budget and Project Period. The total project period for an application submitted in response to this funding opportunity may not exceed two years. Direct costs are limited to $275,000 USD over an R21 two-year period, with no more than $200,000 USD in direct costs in any single year.

Dear President Banda, Vice President Kunda, and Ministers Simbao and Mangani:

Human Rights Watch is a leading independent non-governmental organization, founded in 1978, that monitors human rights developments in more than eighty countries around the world. Since 2001, Human Rights Watch has been monitoring health-related human rights violations in the context of the global HIV epidemic.

In the past three years, Human Rights Watch has issued two reports on HIV and human rights in Zambia: In 2007 we documented how domestic violence affected adherence to HIV treatment, and earlier this year we presented findings on HIV and tuberculosis in prison settings. We acknowledge Zambia's admirable commitment to providing free universal HIV treatment; however, we continue to be concerned that Zambia's goal of combating HIV and AIDS will be undermined by punitive and stigmatizing laws, policies and practices.

We are writing today to draw your attention to the risk posed to the continuing success of Zambia's HIV prevention, testing and treatment campaigns by recent statements first by religious leaders and then government authorities condemning homosexuality. The National HIV/AIDS/STI/TB Council (NAC) of Zambia acknowledged in 2009 that men who have sex with men (MSM) constitute a particularly vulnerable risk group for HIV and AIDS[i] and recognized the "urgent need" to include them in national AIDS strategies.[ii] Zambian activists have informed us, though, that homophobic statements by prominent leaders are already creating a climate of fear among men who have sex with men and threaten to drive this population underground, as activists fear a government crackdown on individuals suspected of being homosexual in Zambia.

Request for Applications (RFA) Number:  RFA-AI-10-012

Key Dates
Opening Date:  October 2, 2010
Letters of Intent Receipt Date(s): October 2, 2010
Application Due Date(s): November 2, 2010 

Overview Content
Purpose. The National Institute of Allergy and Infectious Diseases (NIAID) encourages applications from institutions/organizations to participate in this Funding Opportunity Announcement (FOA), Next Generation PrEP.  The purpose of this FOA is to: develop the basic and preclinical framework needed for development of second and subsequent generations of PrEP agents; create a rational pipeline for the discovery of New Molecular Entities (NMEs) and the identification of existing antiretrovirals (approved for HIV treatment, and those that are not approved but may have extensive clinical data) that can be used for the next generation of PrEP agents; develop preclinical algorithms with clear go/no go criteria for identifying and prioritizing PrEP candidates for advancement to clinical evaluation; generate PK/PD models to assess protective effects at mucosal sites of HIV transmission; and conduct proof-of-concept safety and efficacy studies in animal models.
Mechanism of Support.  This FOA will utilize the NIH Research project (R01) grant mechanism.
Funds Available and Anticipated Number of Awards. NIAID intends to commit approximately $1.8M in FY 2011 to fund 3-5 applications submitted in response to this FOA.