New: GCM's Mapping of Standards of Care Provided in Microbicide Clinical Trials

The Global Campaign for Microbicides (GCM) has just released the first extensive survey mapping the Standards of Care provided in microbicide clinical trials.

Over the years there has been considerable public debate regarding the level of health care and prevention services provided to participants in HIV prevention trials. Although this subject (commonly referred to as the “standards of care” in clinical trials) has been the subject of ethics deliberations in international fora, these discussions have not, historically been informed by an accurate picture of either the daily realities of trial participants or the real-life challenges inherent in implementing trials.

In 2005, the Global Campaign and allied groups posed the following question with the release of a document entitled Consensus Points on Access to Treatment and Standards of Care in Microbicides Trials: "To what extent do conditions on the ground conform to the aspirations of advocates or to the various ethics guidance documents that inform the field?"

To help address this question GCM undertook a systematic mapping exercise of the standards of care provided to participants enrolled in late-stage microbicide trials, as well as one trial evaluating the diaphragm for HIV prevention.

The resulting report, Mapping the Standards of Care at Microbicide Clinical Trial Sites, not only captures the on-the-ground realities and challenges of conducting large-scale HIV prevention trials, but provides insights on how best to inform the design and implementation of future trials as the field moves forward. The report, which details the findings of the exercise and the 28 consensus and author recommendations, is now available for download from the Global Campaign for Microbicides’ website.

Mapping the Standards of Care at Microbicide Clinical Trial Sites
Full Report
Executive Summary

For more information about the standards of care mapping or to receive a printed copy of the report, please contact Katie West Slevin.

SA Aids scientists get government boost

via The Times (South Africa)

Nine groups of South African AIDS researchers will benefit from the Department of Science and Technology’s new research platform launched today.

South African HIV/AIDS Research and Innovation Platform (SHARP) will provide financial support to South African researchers as they explore "every possible avenue to beat the virus".

Read the rest.

DSMB recommends tenofovir gel trial continue

A Data and Safety Monitoring Board (DSMB) held a scheduled review of the CAPRISA 004 Tenofovir Gel Phase IIb trial on 27 July 2009.

This microbicide trial is assessing the safety and effectiveness of 1% tenofovir gel to prevent HIV infection in women in South Africa. It is a collaborative effort between the Centre for the AIDS Programme of Research in South Africa (CAPRISA) at the University of KwaZulu-Natal in Durban, South Africa, Family Health International, and CONRAD. The study is funded by USAID and the South Africa Department of Science and Technology through LIFElab in South Africa.

The DSMB congratulated the study team on trial conduct and recommended that the study continue.

Source: Professor Salim Abdool Karim, Director: CAPRISA, Durban, South Africa

PrEP-related presentations & abstracts from the IAS Conference in Cape Town

[Thank you to Richard Jeffries from the US PrEP Committee for compiling these links.]

Symposium: Antiretroviral Therapy for Prevention: The Time has Come?
Webcast

MOSY403: HIV pre-exposure prophylaxis
PowerPoint by Lynn Paxton (US)

TUPL101: Biomedical Prevention, Including Microbicides, Vaccines, Circumcision and PrEP
Webcast and Powerpoint by Ronald Gray (US)

Oral Abstract Session: ART for Prevention: Critical Issues
Webcast

CDC048: Setting priorities for future antiretroviral-based prevention research: an expert review
Abstract by Y. Halima, J. Mellors, L. Paxton, C. Dieffenbach, E. Bass, C. Collins, K. Fisher, M. Warren (US)

CDC049: Who pays if PrEP works? Potential challenges to PrEP delivery in the United States
Poster by K. Fisher, E. Bass, C. Feuer, D. Grant, L. Miller, M. Warren (US)

CDC093: Building site capacity for HIV prevention research
Abstract and poster by P. Feldblum, C. Sexton, K. MacQueen (US)

CDC098: Ethical appraisal of HIV oral pre-exposure prophylaxis trials: literature review and proposed tool
Poster by M.B. Kokolo (Canada)

MOPED023: Emerging trends in funding for research and development of new HIV prevention options
Poster by K. Fisher, C. Feuer, B. Finley, P. Harrison, W. Lee, L. Romero, S. Vuthoori, M. Warren (US)

MOPED024: Prevention research funding in a global recession: HIV vaccine and microbicide research and development (R&D) trends
Poster by K. Fisher, C. Feuer, B. Finley, P. Harrison, W. Lee, L. Romero, S. Vuthoori, M. Warren (US)

WEPEC079: Characteristics of HIV-1 serodiscordant couples enrolled into a clinical trial of antiretroviral chemoprophylaxis: the Partners PrEP study
Poster by J. Baeten, D. Donnell, A. Mujugira, P. Ndase, N. Mugo (US & Kenya), L. Kidoguchi, L. Barnes, J. Lingappa, C. Celum (US)

WEPEC080: Influence of potential symptoms and perceived efficacy on the willingness to use HIV Pre-Exposure Prophylaxis (PrEP) among Boston area men who have sex with men (MSM)
Abstract by K. Mayer, C. Johnson, M. Mimiaga, S. Safren, P. Case (US)

WEPEC082: Generation of trust between study staff and trial participants enhances participants´ compliance to study procedures in a PrEP trial in the Andes
Poster by P. Goicochea (Peru & US), L. Vargas (Peru), J. Lama (Peru), J. Bernales (Peru), V. McMahan (US), R.M. Grant (US)

WEPEC105: Comparison of acceptability towards circumcision (Circ), pre-exposure prophylaxis (PREP) and herpes simplex suppression (HSV-S) as novel HIV prevention strategies amongst truck drivers in India
Abstract by J. Schneider (US), G. Oruganti (India), S. Pasupneti (US), V. Yeldandi (US), V. Lakshmi (India), R. Dandona (India), K. Mayer (US)

WEPDC103: HIV-associated risk behavior among injecting drug users participating in an HIV pre-exposure prophylaxis trial in Bangkok
Poster by Michael Martin, S. Vanichseni, P. Suntharasamai, U. Sangkum, F. van Griensven, P.A. Mock, R. Chuachoowong, M. Leethochawalit, S. Chiamwongpaet, S. Kittimunkong, K. Choopanya (Thailand)

WEPEC081: Screening, enrollment, and follow-up of injecting drug users in an HIV pre-exposure prophylaxis trial in Bangkok
Poster by M. Martin, S. Vanichseni, P. Suntharasamai, U. Sangkum, R. Chuachoowong, M. Leethochawalit, S. Chiamwongpaet, S. Kittimunkong, P.A. Mock, J. McNicholl, L. Paxton (US), K. Choopanya (all Thailand)

Give Gardasil to boys too, experts say

Source

Recent evidence shows the human papilloma virus (HPV), which causes cervical cancer in women, is poised to become one of the leading causes of oral cancer in men because of changing sexual behaviours.

The findings have reignited the debate over whether boys should be given the cervical cancer vaccine, Gardasil.

A visiting British virologist, Professor Margaret Stanley, says governments around the world need to examine the long-term economic and health benefits of immunising boys and young men.

The head of Microbiology and Infectious Diseases at Melbourne's Royal Women's Hospital, Professor Suzanne Garland, says Australia is leading the way in the rollout of the cervical cancer vaccine Gardasil, which immunises against HPV.

"We are in our third year of rolling out the vaccine and we are in the order in the school-based group, in the high 70s, whereas in many other countries, they have only got 30 per cent who have been vaccinated," she said.

But now the vaccination debate has switched genders.

There are growing calls from the medical community for boys and young men to also be vaccinated against HPV.

Advocates include one of Britain's top cervical cancer specialists, Professor Margaret Stanley from Cambridge University, who says a cervical cancer jab in the arms of boys would not just be for the sake of girls.

"These HPVs don't just cause cancer in women. They cause it in men as well. Cancer in the mouth, cancer in the anus and those cancers are very hard to treat," she said.

Read the rest.

Researchers: Zimbabwe's crisis driving HIV decline

by Michelle Faul, Associated Press

CAPE TOWN, South Africa — Fewer Zimbabweans are getting infected with AIDS, and researchers speculate it's due in part to a battered economy that's leaving men short of money to be sugar daddies and keep mistresses.

Presenting a study of the infection rate among pregnant women at a major international AIDS conference in South Africa this week, Dr. Michael Silverman said the prevalence of the virus that causes AIDS fell from 23 percent in 2001 to 11 percent at the end of 2008. His study was based on tests of 18,746 women at a prenatal clinic in rural Zimbabwe over that period.

Silverman, a Canadian infectious disease expert, works at Howard Hospital in Zimbabwe, where the women were tested.

Silverman said he concluded that "a lot of the effect (of the decline in HIV infections) is from the collapsing economy." AIDS experts have long noted that the richest countries in Africa are also those with the highest infection rates.

"You can't pay the sex worker if you have no currency," he said. "It's hard to have a concurrent relationship if you're always in earshot of your spouse, because you can't afford to travel. Because of the economic collapse, people are forced to stay home, like being in quarantine."

Getting accurate AIDS numbers in Africa, however, has been notoriously difficult since researchers are often forced to guess from imperfect indicators like HIV incidence in pregnant women, instead of counting actual numbers of HIV patients.

Read the rest

High-risk HPV infection raises HIV risk at least fourfold: HPV vaccine study suggested

[From Aidsmap. Article by Gus Cairns and Michael Carter]

Infection with one or more of the cancer-causing subtypes of the human papilloma virus (HPV) multiplied the risk of acquiring HIV among young men in by 4.5-fold in a randomised controlled study of circumcision in South Africa.

Bertran Auvert, the principal investigator of the ANRS1265 circumcision trial in Orange Farm, South Africa, hinted that he was proposing a trial of one of the HPV vaccines as a method of reducing HIV infection.

The substudy of HPV infection collected swabs for DNA analysis from 1683 men and tested them for the presence of 13 of the high-risk, cancer-causing subtypes of HPV and 24 of the low-risk wart-forming ones. HPV samples were collected when the study terminated, 21 months after participants were circumcised.

Observed HPV prevalence was related to the risk of seroconversion during the study and the researchers also related it for the purposes of multivariate analysis to the participants’ age, education level, number of sexual partners, condom use, and whether they had TB or other sexually transmitted infections including herpes, gonorrhoea and chlamydia.

Read the rest on Aidsmap

The Pope, Condoms and the Evolution of HIV

[Enjoy the additional Pope/condom images as light Friday entertainment from IRMA...]

From The Lancet Infectious Diseases, Volume 9, Issue 8, Pages 461 - 462, August 2009.

Samuel Ponce de Leon, et al.

The unjustifiable nature of the Vatican’s opposition to condoms in the face of the spread of HIV has been underlined by many.1 Moreover, the claims made by Pope Benedict XVI during his recent trip to Africa that the AIDS epidemic is a tragedy that “cannot be overcome through the distribution of condoms; on the contrary, they increase it”2 reveal, among other issues, a very poor under standing of the evolutionary future of HIV and the emergence of new strains.

The epidemic has led to the development of highly eff ective therapies based on new antiretroviral drugs, which unfortunately are not available to most African patients. These new treatments have been developed with little consideration of their evolutionary consequences, but HIV will not cease to evolve, as shown by the rapid resistance developed against the different combinations of drugs that are being used.3 Clinical data show that in some parts of Europe and the Americas one of every ten newly infected people has an HIV strain that is already resistant to one or more groups of antiretrovirals.4,5 Unfortunately, the list now includes primary infections in which multidrug-resistant HIV subtypes have been reported.6,7 The unavoidable conclusion is that sooner or later we will observe resistance to even the most efficient combinations of antiretrovirals, with all the clinical and epidemiological adverse consequences.8 Even if we are able to overcome the problems faced in the development of vaccines, they will not be 100% effective.

By contrast, condoms, by their very nature, stop infections but do not act as a selective agent. Pope Benedict XVI, together with physicians, policy makers, religious organisations, and, eventually, the population at large, should become fully aware of the obvious: by acting as a purely physical barrier, condoms not only have a key role in limiting the HIV pandemic, but also help to keep down the number of new strains.

The Vatican must understand that, in purely darwinian terms, HIV will never evolve resistance to condoms.

1 The Lancet. Condoms and the Vatican. Lancet 2008; 367: 1550.
2 The Lancet. Redemption for the Pope? Lancet 2009; 373: 1054.
3 Kantor R, Katzenstein DA, Efron B, et al. Impact of HIV-1 subtype and antiretroviral therapy on protease and reverse transcriptase genotype: results of a global collaboration. PLoS Med 2005; 24: e112.
4 Booth CL, Geretti AM. Prevalence and determinants of transmitted antiretroviral drug resistance in HIV-1 infection. J Antimicrobial Chemother 2007; 59: 1047–56.
5 Vercauteren J, Derdelinckx I, Sasse A, et al. Prevalence and epidemiology of HIV type 1 drug resistance among newly diagnosed therapy-naive patients in Belgium from 2003 to 2006. AIDS Res Hum Retroviruses 2008; 24: 355–62.
6 Blick G, Kagan RM, Coakley E, et al. The probable source of both the primary multidrug-resistant (MDR) HIV-1 strain found in a patient with rapid progression to AIDS and a second recombinant MDR strain found in a chronically HIV-1-infected patient. J Infect Dis 2007; 195: 1250–59.
7 Delaugerre C, Marcelin AG, Soulié C, et al. Transmission of multidrugresistant HIV-1: 5 years of immunological and virological survey. AIDS 2007; 21: 1365–67.
8 Hogg RS, Bangsberg DR, Lima VD, et al. Emergence of drug resistance is associated with an increased risk of death among patients fi rst starting HAART. Plos Med 2006; 3: 1570–78.

Funding for rectal microbicides has DECREASED in two years

According to the latest report just released by the HIV Vaccines and Microbicides Resource Tracking Working Group, funding for rectal microbicides research has decreased significantly in the past 2 years.

When IRMA last tracked resources dedicated to RM research in 2006, we estimated that US$7.2 million was spent globally. According to the report Adapting to Realities: Trends in HIV Prevention Research Funding 2000-2008, released earlier this week, that amount decreased to US$5 million in 2008.

7X more funding needed
In 2006, IRMA called for a five-fold increase in annual funding for rectal microbicide research and development: from about US$7 million to US$35 million per year for the next 10 years. This is what we estimated would be needed – conservatively – to bring at least one effective rectal microbicide through all stages of research.

Now, we need a seven-fold increase from US$5 million to US$35 million.

More diverse funding needed
Nearly 100% of all global investment for rectal microbicides development comes from one source: US public and philanthropic institutions. Most of this US investment comes from the government. While this support is appreciated, a much more diverse funding base is needed.

Where are the governments and research institutions? Where are the foundations?

Australia?
Belgium?
Canada?
Denmark?
France?
Germany?
Ireland?
The Netherlands?
Norway?
Spain?
Sweden?
The UK?
The European Commission?
The Bill & Melinda Gates Foundation?
The Rockefeller Foundation?
UNFPA?
The World Bank?

All of them have contributed to microbicides research, for which we are eternally grateful. But they should also contribute specifically to rectal microbicide research. The entire rectal microbicides field should not be funded solely by the US NIH and amfAR.

Recognised need
It is ironic that in the same time period that saw rectal microbicides become increasingly recognised as an essential component of HIV prevention research, global investment faltered.

Investment in rectal microbicide development MUST INCREASE at this critical time when the HIV prevention field is more willing than ever to acknowledge the need to address the prevention needs of those who engage in anal sex: heterosexual women and men, gay men and other men who have sex with men from around the world – including in Africa, Latin America and the Caribbean, Asia-Pacific, Europe and North America.

Funds needed to move research agenda forward
Exciting research projects are ready to move forward: rectal safety trials, rectal-specific formulation work, lubricant safety, acceptability research, research into incidence, prevalence and context of anal intercourse in various populations around the world. More funding is desperately needed to maintain a robust research agenda.

Read IRMA’s 2006 report: Rectal Microbicides: Investments and Advocacy

Read the HIV Vaccines and Microbicides Resource Tracking Working Group report: Adapting to Realities: Trends in HIV Prevention Research Funding 2000-2008

Read IRMA’s 2008 report: Less Silence, More Science: Advocacy to Make Rectal Microbicides a Reality





Join efforts to advocate for more investment in rectal microbicide development!

Africa Sings... And Dances

by Jim Pickett

One of my most inspiring days at the IAS 2009 conference - or any conference in my life for that matter - was my visit to two HIV/AIDS programs in the Cape Town area. Courtesy of Bristol Myers Squibb (who provides funding to these projects) a horde of European journalists and a couple of lone Americans got on a bus and visited Grandmothers Against Poverty and AIDS (GAPA) in Khayelitsha - a huge township (around a million people) just outside Cape Town. GAPA provides support to "grannies" who have lost their children to AIDS and are in the position of having to raise their grandchildren and manage their grief.

We then went to Paarl (wine country) and visited the Butterfly House - a community of "love in action" that provides care for people impacted by HIV, including home-based care and programming for young people, many of whom have lost parents to HIV.

We were treated to lunch at GAPA, and in both locations dance performances and lots and lots of singing.

The pictures speak for themselves. But my favorite quote of the day was when the director of GAPA, Ms Mandisa Mafuya, said, "In Africa, we sing. We sing when we are happy, and when we are sad. We sing when we are angry. We sing when we are confused. We just sing."

And they did.

High Occurrence in Africa of HIV among Homosexual Men Study Finds

via LifeSiteNews.com, by Patrick B. Craine

A new literature review, published by The Lancet, emphasizes the great proportion of HIV/AIDS cases among men who have sex with men (MSM) in sub-Saharan Africa, a fact often ignored in the fight against AIDS in Africa. The study concludes, however, that the solution to the problem lies in greater openness to homosexual practices from the African nations and better access to interventions, a solution that experts from the National Association for Research and Therapy of Homosexuality (NARTH) have called "simplistic."

The review, principally authored by Dr. Adrian D. Smith of the University of Oxford, calls for greater acceptance of MSM in sub-Saharan Africa, where the cultures are still mostly unwilling to accept homosexuality and the homosexualist agenda.

"Continued denial of MSM from effective HIV/AIDS prevention and care," they say, "is harmful to national HIV/AIDS responses." According to the review, male-to-male sex is illegal in 31 sub-Saharan countries, with the death penalty a possible punishment in four of them.

There is a need, say the researchers, for increased recognition of the HIV problem among MSM, which has been overlooked in sub-Saharan Africa. "Globally, [MSM] continue to bear a high burden of HIV infection," they write.

The initial research conducted in the early 1980s focused on heterosexual transmission, observe the researchers, suggesting that these findings have skewed the approach ever since. The result was that "the possibility that MSM might feature within this model [of HIV infection in Africa] soon disappeared from discussion."

Previous reports have also indicated that the idea that AIDS is primarily being transmitted through heterosexual relations in Africa may not have a firm basis in fact.

In 2003 a study authored by Dr. Stuart Brody found that anal sex, both homosexual and heterosexual, is the second greatest cause of HIV transmission in Africa. Poor medical practices, such as the use of dirty needles, were found to be the greatest cause, with vaginal transmission being a distant third cause.

Read the rest.

Study: Circumcision Protects Insertive MSM Partners

via AIDSmeds.com, by Tim Horn

Circumcision may protect men who have sex with men (MSM) against HIV transmission via insertive anal intercourse, according to a cohort study conducted in Soweto, South Africa, and reported Monday, July 20, at the Fifth International AIDS Society (IAS) Conference on HIV Pathogenesis, Treatment and Prevention in Cape Town.

Read the rest.

Plenaries announced for LGBTI Health Summit

Organizers of the 2009 National LGBTI Health Summit announced that, in collaboration with the Bisexual Health Summit, five lunch time plenaries will serve as features of the Summit. The plenaries include a keynote by Cheryl Dobinson on bisexual health disparities (during the Bisexual Health Summit), a national conversation among gay mayors and LGBT liaisons from around the country, a discussion on the present and future sustainability of LGBTI health movement building, “Count Us In! How and Why To Include LGBTIs in Data Collection” a talk on LGBTI-inclusive research, and “Elder Sexual: HIV and Aging,” a dialogue on the issues of HIV and aging. The plenaries are sponsored by the Adler School of Professional Psychology, Roosevelt University, and Tibotec.

“The plenary topics illustrate many of the pressing issues in LGBTI health,” said Catherine Jefcoat, Director of the Lesbian Community Care Project at Howard Brown Health Center and a co-chair of National LGBTI Health Summit. “These four topics reflect the comprehensive nature of the Summit. We hope to use the plenaries as a catalyst for conversation and vision-setting.”

The Summit begins the morning of Friday, August 14 with a day devoted specifically to Bisexual Health and the needs, opportunities and challenges of the Bisexual Community. Saturday, August 15 kicks off the full LGBTI Health Summit which continues through Tuesday, August 18.

The full topic workshop schedule is posted on the website.


Philadelphia hosted the last National LGBTI Health Summit in 2007. This year’s Summit in Chicago – at the Chicago Hilton and Towers – will be the fourth gathering of its kind. Sponsors include Center on Halsted, Test Positive Aware Network, Chicago Hilton Hotel and Towers, the Chicago Department of Public Health’s Office of LGBT Health, AIDS Foundation of Chicago, Howard Brown Health Center, Adler School of Psychology, Blue Cross Blue Shield of Illinois and Sidetrack among others. Organizers may be contacted through the Summit website www.2009lgbtihealth.org.

Rates of HIV among MSM in Africa: A Review

IRMA is thrilled to see an increase in attention to this issue in the past two years.

The Lancet has just published a review of studies that could provide information on HIV prevalence rates among MSM in Africa. The summary and link to the full article can be found below, as is a glimpse at a BBC News article on the subject.

Men who have sex with men and HIV/AIDS in sub-Saharan Africa
Adrian D Smith, Placide Tapsoba, Norbert Peshu, Eduard J Sanders, Harold W Jaffe

The Lancet, Early Online Publication, 20 July 2009

SUMMARY

Globally, men who have sex with men (MSM) continue to bear a high burden of HIV infection. In sub-Saharan Africa, same-sex behaviours have been largely neglected by HIV research up to now. The results from recent studies, however, indicate the widespread existence of MSM groups across Africa, and high rates of HIV infection, HIV risk behaviour, and evidence of behavioural links between MSM and heterosexual networks have been reported. Yet most African MSM have no safe access to relevant HIV/AIDS information and services, and many African states have not begun to recognise or address the needs of these men in the context of national HIV/AIDS prevention and control programmes. The HIV/AIDS community now has considerable challenges in clarifying and addressing the needs of MSM in sub-Saharan Africa; homosexuality is illegal in most countries, and political and social hostility are endemic. An effective response to HIV/AIDS requires improved strategic information about all risk groups, including MSM. The belated response to MSM with HIV infection needs rapid and sustained national and international commitment to the development of appropriate interventions and action to reduce structural and social barriers to make these accessible.

Read the full Lancet review

BBC News: Alarming Africa male gay HIV rate

HIV rates among gay men in some African countries are 10 times higher than among the general male population, says research in medical journal the Lancet.

The report said prejudice towards gay people was leading to isolation and harassment, which in turn led to risky sexual practices among gay communities.

But the risks are not limited to gay men, as many of the infected also have female sexual partners.

The report called for greater education and resources in the fight against HIV.

The Oxford University researchers found that the prevalence of HIV/Aids among gay men in sub-Saharan African has been "driven by cultural, religious and political unwillingness to accept [gay men] as equal members of society".

Read the rest of the BBC News article

Rectal Microbicide Development - An African Perspective - THIS SUNDAY at IAS 2009

Please plan to join IRMA and colleagues for this exciting satellite session on Sunday, July 19 in Cape Town, South Africa

Click to enlarge

The Lancet publishes results from Uganda trial: Showed that circumcising HIV+ men did not protect women

"Circumcision in HIV-infected men and its effect on HIV transmission to female partners in Rakai, Uganda: a randomised controlled trial."

Maria J Wawer, Frederick Makumbi, Godfrey Kigozi, David Serwadda, Stephen Watya, Fred Nalugoda, Dennis Buwembo, Victor Ssempijja, Noah Kiwanuka, Lawrence H Moulton, Nelson K Sewankambo, Steven J Reynolds, Thomas C Quinn, Pius Opendi, Boaz Iga, Renee Ridzon, Oliver Laeyendecker, Ronald H Gray.

The Lancet, Volume 374, Issue 9685, Pages 229 - 237, 18 July 2009
DOI: 10.1016/S0140-6736(09)60998-3

Background: Observational studies have reported an association between male circumcision and reduced risk of HIV infection in female partners. We assessed whether circumcision in HIV-infected men would reduce transmission of the virus to female sexual partners.

Methods: 922 uncircumcised, HIV-infected, asymptomatic men aged 15—49 years with CD4-cell counts 350 cells per μL or more were enrolled in this unblinded, randomised controlled trial in Rakai District, Uganda. Men were randomly assigned by computer-generated randomisation sequence to receive immediate circumcision (intervention; n=474) or circumcision delayed for 24 months (control; n=448). HIV-uninfected female partners of the randomised men were concurrently enrolled (intervention, n=93; control, n=70) and followed up at 6, 12, and 24 months, to assess HIV acquisition by male treatment assignment (primary outcome). A modified intention-to-treat (ITT) analysis, which included all concurrently enrolled couples in which the female partner had at least one follow-up visit over 24 months, assessed female HIV acquisition by use of survival analysis and Cox proportional hazards modelling. This trial is registered with ClinicalTrials.gov, number NCT00124878.

Findings: The trial was stopped early because of futility. 92 couples in the intervention group and 67 couples in the control group were included in the modified ITT analysis. 17 (18%) women in the intervention group and eight (12%) women in the control group acquired HIV during follow-up (p=0·36). Cumulative probabilities of female HIV infection at 24 months were 21·7% (95% CI 12·7—33·4) in the intervention group and 13·4% (6·7—25·8) in the control group (adjusted hazard ratio 1·49, 95% CI 0·62—3·57; p=0·368).

Interpretation: Circumcision of HIV-infected men did not reduce HIV transmission to female partners over 24 months; longer-term effects could not be assessed. Condom use after male circumcision is essential for HIV prevention.

Funding: Bill & Melinda Gates Foundation with additional laboratory and training support from the National Institutes of Health and the Fogarty International Center.

Read the full article

[IRMA reminds readers that two trials have shown that circumcised men were 50 to 60 percent less likely to get HIV from having (what is presumed to be mostly) vaginal sex. This does not mean that circumcised men cannot get or transmit HIV. It only means that they are about half as likely as uncircumcised men to get HIV from having vaginal sex with a woman who has HIV.

Trial data also do not show whether circumcision lowers the risk of transmission for either men or women during unprotected anal sex.]

Unprotected sex between HIV-infected partners keeps immune responses activated

Crabb, Charlene

AIDS. 23(11):N7, July 17, 2009.

HIV acts as a ‘natural immunogen’, keeping anti-HIV-1 immune responses boosted in HIV-infected male couples who have unprotected sex, say University of California San Francisco researchers [original article from UCSF researchers: PLoS Pathog 2008; 4:e1000185].

Until now, little has been reported on the consequences of continued exposure to HIV in people who are already infected. But serosorting, the practice of identifying sexual partners based on their HIV status, is a growing trend. It often leads to unprotected sex between HIV infected individuals, which poses the risk of acquiring a drug-resistant strain of the virus.

To shed light on the immunological consequences of continued exposure to HIV, Christian Willberg and colleagues studied 49 men, from a San Francisco prospective cohort of couples in long-term relationships, who were suppressing their virus below the detection level (50RNAcopies/ml) with HAART. Twenty-nine men had partners whose virus was also in check due to antiviral therapy, whereas 20 men had viremic partners whose viral loads were more than 90 000RNAcopies/ml.

Using enzyme-linked immunosorbent spot (ELISPOT) assay to compare HIV-1-specific T-cell responses between the two groups, the researchers found significantly stronger (P¼0.001) responses against HIV-1 protease, reverse transcriptase, and integrase peptides in the men with viremic partners. The magnitude of their responses correlated with a greater frequency of unprotected sex, and in particular with the frequency of exposure through receptive (versus insertive) anal sex. No similar correlations were found in the men with nonviremic partners.

‘Rather than losing responses because their own virus has been suppressed by antiviral therapy,’ explains Willberg, ‘we found that the men are maintaining a response because they are constantly being exposed to their partner’s virus.’

That the amount of exposure drives the boosted HIV-1- specific immune responses was also illustrated in three individuals from the viremic partner group whose T-cell responses dropped significantly a year later. Two had partners who started antiretroviral therapy and were suppressing their viral loads. The third had reduced his exposure. (Seven individuals from the viremic partner group had blood samples available froma 1-year followup.)

The researchers note that superinfection is the most likely mechanism to maintain or boost the HIV-1 immune responses. However, HIV-1 sequencing of all participants in the study found no evidence of superinfection at the systemic level in which a new virus overgrows the existing strain. Willberg, who is now at Oxford University, cautions that the study’s phylogenetic analysis does not rule out localized superinfections in the gut, most likely the rectum.

Furthermore, no one knows whether maintaining a high T-cell response is good or bad. Willberg says that keeping an active HIV-1 immune response might help control viral rebound in a person when antiviral therapy fails for some reason, or it could indicate a compartmentalized superinfection and the increased risk of acquiring a drug-resistant strain. ‘It could be a double-edged sword,’ he says.

Sexual transmission of HIV according to viral load and antiretroviral therapy: systematic review and meta-analysis

Attia, Suzanna; Egger, Matthias; Müller, Monika; Zwahlen, Marcel; Low, Nicola

AIDS: 17 July 2009 - Volume 23 - Issue 11 - p 1397-1404

Objectives: To synthesize the evidence on the risk of HIV transmission through unprotected sexual intercourse according to viral load and treatment with combination antiretroviral therapy (ART).

Design: Systematic review and meta-analysis.

Methods: We searched Medline, Embase and conference abstracts from 1996-2009. We included longitudinal studies of serodiscordant couples reporting on HIV transmission according to plasma viral load or use of ART and used random-effects Poisson regression models to obtain summary transmission rates [with 95% confidence intervals, (CI)]. If there were no transmission events we estimated an upper 97.5% confidence limit.

Results: We identified 11 cohorts reporting on 5021 heterosexual couples and 461 HIV-transmission events. The rate of transmission overall from ART-treated patients was 0.46 (95% CI 0.19-1.09) per 100 person-years, based on five events. The transmission rate from a seropositive partner with viral load below 400 copies/ml on ART, based on two studies, was zero with an upper 97.5% confidence limit of 1.27 per 100 person-years, and 0.16 (95% CI 0.02-1.13) per 100 person-years if not on ART, based on five studies and one event. There were insufficient data to calculate rates according to the presence or absence of sexually transmitted infections, condom use, or vaginal or anal intercourse.

Conclusion: Studies of heterosexual discordant couples observed no transmission in patients treated with ART and with viral load below 400 copies/ml, but data were compatible with one transmission per 79 person-years. Further studies are needed to better define the risk of HIV transmission from patients on ART.

South Africa: Lesbians and HIV: Low risk but not no risk

JOHANNESBURG, 14 July 2009 (PlusNews) - Women who sleep with women (WSW) are not at risk of HIV transmission – or are they? AIDS advocates warn that it is time for a wake-up call about who is and is not at risk.

HIV prevention among WSW and lesbian women remains off the prevention agenda, said Beverley Palesa Ditsie, a founding member of the Gay and Lesbian Organization of the Witwatersrand.

"When it comes to same-sex relationships other than male-to-male, [HIV] transmission is something we think we don't have to talk about," she commented at the launch of a new book on same-sex sexuality and HIV, published by the Human Sciences Research Council.

Zethu Matebeni, a fellow at the University of Witwatersrand's Institute for Social and Economic Research (WISER), who spent three years studying Johannesburg's black lesbian community, agreed that myths about the risk of female-to-female transmission were not being adequately addressed.

Rape as punishment

No data exists on HIV prevalence among lesbian women or WSW globally or in South Africa, but limited research by the gay and lesbian organization, OUT, indicated that the high rates of HIV in the WSW interviewed could be attributed mainly to rape, transactional sex and sexual violence.

Lesbian women in South Africa are being raped by men who believe it will "cure" them of their sexual orientation; women in townships in Johannesburg and Cape Town report a rising tide of brutal homophobic attacks, murders, and the widespread use of "corrective" rape as a form of punishment, notes a report published earlier this year by the international NGO, ActionAid.

According to OUT's research, only about 40 percent of WSW knew their HIV status, which often carried the same burden of stigma and silence it would in any relationship, Matebeni told IRIN/PlusNews. "Some women say it makes your partners think you have been sleeping around when it's not the case."

She said negotiating safe sex could be difficult for women even in loving, consensual relationships. It was also difficult to access barrier methods like finger condoms or dental dams - thin squares of latex rubber placed over the vagina or anus during oral sex to prevent sexually transmitted infections.

"Often, we don't know how to talk about safer sex because there aren't protection methods and, of the ones that are out there, many of them are extremely unpleasant – they make you feel ugly, and feeling beautiful is very important in sex."

Matebeni called for more attention to the HIV-prevention needs of women in same-sex relationships.

Gender differences in immune response to HIV

From Kaiser News

New research showing that "a receptor molecule involved in the recognition of HIV-1 responds to the virus differently in women than in men," might "explain why HIV infection progresses faster to AIDS in women than in men with similar viral loads," the HealthDay/Greenville Daily Reflector reports. The study was conducted by researchers at the Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University and will be published in an upcoming issue of the journal Nature Medicine. Study authors also note that during the early stages of infection, women tend to have a stronger immune response to HIV than men, but then progress to AIDS more quickly. The different immune system response "then leads to differences in chronic T-cell activation, a known activator of disease progression, according to the researchers," the article states (7/13). Researcher Marcus Altfeld said the findings raise new questions about how sex hormones affect HIV in the body. "Focusing on immune activation separately from viral replication might give us new therapeutic approaches" to treating HIV, he added (AFP/Google News, 7/13).

New Lab Test Offers Better Prediction of Microbicide Safety

Newswise — Scientists at Albert Einstein College of Medicine of Yeshiva University have devised a laboratory test for predicting whether microbicides against HIV are safe for human use. The researchers have also discovered why several supposedly “safe” microbicides made women more susceptible to HIV infection. The study appears today in the online version of the Journal of Infectious Diseases.

For years, scientists have been trying to develop a topical vaginal microbicide for preventing transmission of HIV, the virus that causes AIDS. A safe and effective microbicide would help protect women in settings where male condoms are not used — a common situation in many cultures. The need for an HIV microbicide is especially urgent in Africa, where AIDS is the leading cause of death and where women account for six out of ten of those living with HIV.

Several microbicide gels have been assessed in clinical trials after passing laboratory and animal safety tests. But with just one exception, all the microbicides were found to be ineffective against HIV; and two of the gels — nonoxynol-9 and cellulose sulfate — actually increased the risk of HIV infection in women.

“Our goal was to develop assays that are predictive of safety before proceeding to clinical trials that typically cost millions of dollars, involve thousands of women, and take many years,” says study leader Betsy C. Herold, M.D., professor of pediatrics, of microbiology & immunology, and of obstetrics & gynecology and women’s health at Einstein.

In evaluating a microbicide’s safety, researchers look primarily for signs that the chemical inflames cells of the vaginal lining, or epithelium. That could cause more harm than good: When the epithelium becomes inflamed, T cells flock to the damaged area — which might actually encourage HIV infection, since T cells are the main targets of HIV.

Dr. Herold theorized that another mechanism may also compromise a microbicide’s safety. The cells of the vaginal epithelium normally are tightly packed together, forming an impermeable barrier to HIV. If a microbicide disrupts the barrier’s structural integrity, HIV would be able to slip through the gaps and infect circulating T cells.

To test this theory, Pedro Mesquita, a postdoctoral fellow in Dr. Herold’s lab, developed a model that mimicked the genital tract environment. It was composed of two chambers separated by a barrier of cultured human cells that form tight junctions. After treating the epithelial cells with different microbicides, the researchers tested the barrier’s permeability to HIV by placing HIV in the upper chamber, T cells in the lower chamber, and then monitoring the infection of the T cells over time.

When the epithelial barrier was treated with placebo, HIV was unable to pass through to the lower chamber, leaving the T cells uninfected. “But when we applied nonoxynol-9, the virus went right through the barrier and infected the T cells,” says Dr. Herold. This result was no surprise, since nonoxynol-9 is a detergent, a class of chemicals known to be disruptive to cells.

Read the rest

Tight junctions between genital tract epithelial cells provide an anatomic barrier and prevent HIV from reaching submucosal targets. Microbicides that disrupt the barrier increase the risk for HIV infection. This assay accurately predicts the safety of microbicides.

From Spain: Microbicides and Gender: An Open Debate

Planeta Salud organized a roundtable discussion in Barcelona on May 26th, 2009, to analyze and discuss the issues surrounding microbicides and their potential effects on gender, power roles and sexual health within a Spanish context.

The event was attended by more than twenty participants representing a variety of fields such as women’s rights, gender issues, HIV/AIDS prevention, immigrant populations and the health administration. The multidisciplinary nature of the audience permitted a wide range of comments, observations and critiques to be expressed, offering a panoramic look into the HIV prevention context.

Participants discussed a wide range of issues, including: the realities of sexual prevention today, how microbicide introduction can build on lessons learned from participants’ experiences, risk reduction approaches, how men and women can work together on HIV prevention, the challenges of products with partial efficacy, and the need for sufficient funding, training and integration of microbicides into existing programs.

Many participants expressed interest in rectal microbicides, providing an opportunity for discussion and distribution of IRMA materials.

Planeta Salud will follow up with further sessions, awareness-raising and meetings with political stakeholders.

Does sex in the early period after circumcision increase HIV-seroconversion risk?

Does sex in the early period after circumcision increase HIV-seroconversion risk? Pooled analysis of adult male circumcision clinical trials. AIDS, 29 June 2009, epub ahead of print.

Mehta SD, et al. (Division of Epidemiology and Biostatistics, School of Public Health, University of Illinois at Chicago, Chicago, Illinois, USA)

OBJECTIVE: To evaluate whether sexual intercourse soon after adult male circumcision affected HIV risk.

DESIGN: Combined analysis of data from African trials of men who were randomized to and underwent circumcision.

METHODS: We examined two associations: early sex (intercourse <42 days after circumcision) and HIV acquisition at 3 months for the Orange Farm and Kisumu trials and at 6 months for the Rakai and Kisumu trials and incomplete wound healing at 1 month and seroconversion at 3 and 6 months for the Kisumu trial and at 6 months for the Rakai trial.

RESULTS: Early sex was reported by 3.9% of participants in Kisumu, 5.4% in Rakai, and 22.5% in Orange Farm. HIV seroprevalence was 0.0% at 3 months and 1.9% at 6 months among 18-24-year-olds reporting early sex and 0.2% at 3 months and 0.6% at 6 months among those who did not report early sex. In pooled analyses, men reporting early sex did not have higher HIV infection risk at 3 or 6 months. In Kisumu, 16 (1.3%) men had incomplete wound healing at the 30-day visit. One (6.3%) of these seroconverted at 3 months compared with 2 (0.2%) of 1246 men with complete wound healing (P = 0.075). No association was observed between incomplete wound healing and seroconversion for Rakai participants.

CONCLUSION: Most men delayed intercourse after circumcision. Early sex after circumcision was not associated with HIV risk, although the study power was limited. Nevertheless, men should delay intercourse to limit the potential for increased HIV risk until complete wound healing.

PMID: 19571722 [PubMed - as supplied by publisher]

[IRMA reminds readers that circumcised men in these trials were 50 to 60 percent less likely to get HIV from having (what is presumed to be mostly) vaginal sex. This does not mean that circumcised men cannot get or transmit HIV. It only means that they are about half as likely as uncircumcised men to get HIV from having vaginal sex with a woman who has HIV.

Trial data have not shown that circumcision makes a man less likely to transmit HIV to his partner through vaginal sex. In fact, one trial showed the opposite. This trial enrolled Ugandan married couples in which the husbands were HIV-positive and wives were HIV-negative. The wives of the men who got circumcised in this trial appeared to be at greater risk of getting HIV than the women married to uncircumcised men. The increased risk may have occurred when couples started having sex again before the skin on the man’s penis had fully healed (become keratinised) – a process that takes about six weeks.

Trial data also do not show whether circumcision lowers the risk of transmission for either men or women during unprotected anal sex.]

For more on male circumcision.

For more on what male circumcision means for women.

HIV serosorting and the risk of STIs in MSM

[Presented at SÖDAK 2009: The German-Austrian-Swiss AIDS Congress, June 24-27 2009]

Marcus ULRICH and Axel J. SCHMIDT (Robert Koch Institut)

Objectives: We aimed to quantify the frequency and effectiveness of HIV risk management strategies and tactics other than condom use among men who have sex with men (MSM) in Germany and their impact on the frequency of sexually transmitted infections (STI).

Methods: For a cross-sectional survey a self-administered questionnaire was distributed via German MSM websites and medical practices in 2006. The majority (87%) of 6,833 analyzed participants were recruited online. We analyzed risk management of participants who reported HIVserosorting as a strategy (premeditated, planned) or as a tactic (depending on the situation) and explored the impact of HIV serosorting on the incidence of self-reported bacterial STIs by comparing serosorters with participants who reported other forms of risk management.

Results: HIV status has a large impact on the way how HIV serosorting is implemented. While HIV serosorting used strategically and tactically seems to be very similar in HIV positive MSM, there are distinct differences between HIV negative strategic and tactic serosorting. Except for HIV negative strategic serosorters, serosorting is associated with reduced condom use, higher partner numbers and a two to four fold increased risk of being diagnosed with bacterial STIs.

Discussion: HIV serosorting within primary relationships as well as with casual partners has emerged as a common risk management strategy and tactic in MSM. Apart from the problems of unambiguous communication about HIV status and the reliability of an HIV negative serostatus information, HIV serosorting as practiced currently by MSM in Germany is often used as an alternative to condoms, contributes to high incidences of STIs and hence elevated per-contact-risks for HIV transmission. Exclusive emphasis on HIV testing may encourage HIV serosorting, and thus may not solve the problems of HIV prevention, mainly because it lacks a comprehensive sexual risk reduction strategy for ART-naïve MSM diagnosed with HIV.

Slides from the presentation (in German)

Rectal Microbicide Development - An African Perspective - IAS 2009

Please plan to join IRMA and colleagues for this exciting satellite session on Sunday, July 19 in Cape Town, South Africa

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Heterosexual Anal Intercourse among Community and Clinical Settings in Cape Town, South Africa

Seth Kalichman (1), Leickness Simbayi (2), Demetria Cain (1) and Sean Jooste (2)

1 University of Connecticut, United States
2 HSRC Cape Town, South Africa

Sex Transm Infect. Published Online First: 7 May 2009. doi:10.1136/sti.2008.035287
Copyright © 2009 by the BMJ Publishing Group Ltd. Accepted 28 April 2009.

Abstract

Background: Anal intercourse is an efficient mode of HIV transmission and may play a role in heterosexual HIV epidemics of southern Africa. However, little information is available on the anal sex practices of heterosexuals in South Africa.

Purpose: To examine the occurrence of anal intercourse in samples drawn from community and clinic settings.

Methods: Anonymous surveys collected from convenience samples of 2593 men and 1818 women in two townships and one large city STI clinic in Cape Town. Measures included demographics, HIV risk history, substance use, and three month retrospective sexual behavior.

Results: A total of 14% (n = 360) men and 10% (n = 172) women reported engaging in anal intercourse in the past three months. Men used condoms during 67% and women 50% of anal intercourse occasions. Anal intercourse was associated with younger age, being unmarried,having a history of STIs, exchanging sex, using substances, having been tested for HIV, and testing HIV positive.

Conclusions: Anal intercourse is reported relatively less frequently than unprotected vaginal intercourse among heterosexuals. The low prevalence of anal intercourse among heterosexuals may be offset by its greater efficiency for transmitting HIV. Anal sex should be discussed in heterosexual HIV prevention programming.

The HPV Vaccine for Men: Yes or No?

IRMA would love to hear your thoughts and comments...

1. Last month, IRMA member Robert Reinhard shared the news story from Bloomberg that "Merck's Guardasil May Not Be Cost Effective in Boys", wondering whther the Harvard study mentioned in the article sufficiently addressed cost effectiveness and use of the HPV vaccine for MSM, even allowing for the ambiguity of what that group looks like in populations <26>

"Vaccinating all boys with Merck & Co.’s Gardasil, used to prevent cervical cancer, may be less cost effective than for girls, a study said.

The improvement in quality and length of life may not be worth the cost of vaccinating boys with Gardasil to protect against the spread of the sexually transmitted virus that causes cancers of the cervix, anus and penis, according to an analysis by Harvard researchers. The study was presented today to advisers to the U.S. Centers for Disease Control and Prevention. Health officials should focus on vaccinating girls, said the study authors.

The research differs from Merck’s analysis of boys and young men up to age 26 that found vaccinating them with Gardasil was cost effective. Vaccinating males may help prevent them from spreading the cancer-causing human papillomavirus, or HPV, to women as well as protect them against genital warts and pre- cancerous lesions, Merck said. CDC’s Advisory Committee on Immunization Practices plans to vote in October about whether Gardasil should routinely be given to boys."

2. IRMA member Mark Hubbard then shared the presentation from Dr. Anna Giuliano on HPV in Males: The Future of Vaccination to Prevent Cancer, making a case for male vaccination.

3. Finally, a recent article from Xtra, the Canadian gay and lebian newspaper, reports that a University of California, San Francisco study funded by Merck found that vaccination for males is cost effective. The article reports:

"Palefsky [the lead researcher from the UCSF study] says the vaccine would still make an effective preventative health tool for everyone because the same strains of HPV that cause most cervical cancers in women also cause a majority of anal cancers in men.

“They’re entirely the same,” he says. “That’s why we’re optimistic that if boys do get vaccinated with the same vaccine that girls are using, it should prevent a substantial number of anal cancers.”

HPV is sexually transmitted. The US Centers for Disease Control suggests that gay men are as many as 17 times more likely to develop anal cancer than are heterosexual men.

“On a per-individual basis the risk is clearly much higher in MSM than the general population,” says Palefsky. “That’s presumably due to anal sex, though we also know that you don’t have to have anal sex to get anal HPV infection.”

What are YOUR thoughts? HPV vaccine for all men? Gay men and other MSM only? Provided to boys or adults? Still for girls only?

Follow the IAS 2009 Live - Via Blog

IAS 2009 Live tracks the latest developments from the 5th IAS Conference on HIV Pathogenesis, Treatment and Prevention. We'll highlight new research and information on http://www.ias2009.org/ along with news reports from Cape Town. Scientists and community and policy leaders will also blog about their observations.