Professor Salim Abdool Karim and his team showing CAPRISA’s Ethekweni research facility to UNAIDS Executive Director Michel Sidibé

In 2010 an announcement was made by the Centre for the AIDS Programme of Research in South Africa (CAPRISA) which rocked the AIDS world and promised hope for millions of women around the world.

The researchers discovered that the antiretroviral medicine tenofovir, when applied to the vagina in gel form, is effective in reducing HIV infections in women by up to 54%.

The discovery was made by Professor Salim Abdool Karim and the team at CAPRISA’s Ethekweni research facility. The centre is located in a historic building built in 1946, originally home to the Durban Chest Clinic, a state-run Tuberculosis facility.

In 2000 the local government built the new state of the art Prince Cyril Zulu Communicable Diseases clinic adjoining the old building which was designed specifically to minimize the risk of cross infection among patients.

It is the largest TB centre of its kind in South Africa, with specially designed ventilation to encourage an in out air flow, vast open waiting areas to reduce the risk of cross infection and huge skylights which enable the suns rays which destroy the TB.

The facility is located in central Durban, in the heart of the transport hub for public commuters by rail, bus or minibus taxis.

“This means that the clinic receives a lot of walk-in patients”, explained Santhana Gengiah, Study Coordinator at CAPRISA.  “Accessibility and convenience for clients is paramount”.

The venue provided the perfect location for Professor Karim and his team to set up their HIV research programme as the TB clinic which also has a sexually transmitted infection centre on the first floor, found that around 70% of the patients coming into the clinic also were testing positive for HIV.  

The CAPRISA eThekwini site comprises two sections, a Treatment Clinic for HIV-TB co-infected patients and an HIV prevention clinic.  The prevention section has hosted a number of notable microbicide scientific trials, including the CAPRISA 004 trial and the recently modified Vaginal and Oral Interventions to Control the Epidemic (VOICE) study.

Professor Salim Abdool Karim (left) and UNAIDS Executive Director Michel Sidibé

VOICE is an HIV prevention trial evaluation two antiretroviral based approaches for preventing sexual transmission of HIV in women––daily use of one of two different ARV tablets (tenofovir and Truvada) or of a vaginal gel. The Data and Safety Monitoring Board recommended that VOICE participants in the oral tenofovir arm of the study discontinue their use of the product as the trial was not able to demonstrate that the tablets were effective in preventing HIV in the women enrolled in the trial. VOICE will however continue to test the efficacy of the other oral tablet Truvada and the vaginal gel formulation of tenofovir.

The treatment section of the clinic is perhaps best known for the groundbreaking SAPiT trial, which provided essential evidence for HIV/TB treatment guidelines and informed the current World Health Organization guidelines on the treatment of TB in HIV-positive patients.

The Executive Director of UNAIDS Michel Sidibé recently paid a visit to both the CAPRISA and Prince Cyril Zulu sites, and was impressed by the innovative work being carried out in the name of science and service delivery.

“This is a great example of how scientific innovation meets implementation”, he said. “The scientific research being done here gives hope to millions of men, women and children who will lead a longer, healthier life because of these important discoveries”.

Credit: UNAIDS/P. Virot

The Lancet Infectious Diseases today published evidence from a World Health Organization-led study. The study showed that giving pregnant women living with HIV a combination of three antiretroviral (ARV) drugs from the last trimester, through delivery and six months of breastfeeding can reduce the risk of their babies being infected with HIV by more than 40%.

The study, named Kesho Bora which means ‘a better future’ in Swahili, was conducted between June 2005 and August 2008 in five sites in Burkina Faso, Kenya and South Africa. The randomized controlled trial aimed to assess the efficacy and safety of triple antiretroviral treatment to reduce mother-to-child transmission of HIV. This was compared to the use of single-dose nevirapine and zidovudine stopped after delivery, as had been recommended by the World Health Organization (WHO) since 2004.

Triple antiretroviral treatment given to pregnant women with a CD4 immune cell count of 200-500 cells/mm3 starting in their last trimester reduced mother-to-child transmission by 43% and reduced the risk of infection during breast-feeding by more than half. It was also shown to be safe for both mother and baby.

The WHO’s Department of Reproductive Health and Research worked in partnership on the study with the French National Agency for Research on AIDS and Viral Hepatitis (ANRS), the US Centers for Disease Control and Prevention (CDC) and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) of the National Institutes of Health.

After nearly 20 years of research, the results of the CAPRISA 004 trial provided the first evidence that the use of a vaginal microbicide could provide a safe and effective way to prevent HIV infection in women.

Following results from a South African study (CAPRISA 004) showing that a vaginal microbicide gel containing the antiretroviral drug tenofovir was 39% effective in reducing a woman’s risk of becoming infected with HIV during sex, WHO and UNAIDS convened a meeting in August 2010, just a month following the announcement, to review the implications of the CAPRISA 004 results and determine the appropriate next steps.

The meeting participants agreed on the below priority actions for follow-up:

• Additional safety studies;
• Effectiveness trial in South Africa to confirm the CAPRISA 004 BAT 24 dosing regimen;
• Effectiveness and safety trial of simplified dosing and HIV testing schedules;
• Implementation study in South Africa; and,
• Treatment outcome and resistance study.

To find out more, read the executive summary of the meeting report , or download the full report.

Credit: UNAIDS/A. Gutman

As the world marks International Women’s Day, there is growing concern that women and children are bearing the brunt of the AIDS epidemic. To turn the tide, UNAIDS, the International AIDS Society (IAS) and 14 other leading public and private sector organizations have teamed up to release a new scientific research agenda.

The report called, “Asking the Right Questions: Advancing an HIV Research Agenda for Women and Children” includes 20 specific recommendations to expand and improve responses to the HIV-related challenges facing women and children worldwide.

“With this roadmap, we can work together to remove the roadblocks to universal access to HIV prevention and treatment and move forward to a world where women and children are no longer left behind,” said UNAIDS Executive Director Mr Michel Sidibé.

HIV is the leading cause of death and disease among women of reproductive age. The majority of the estimated 33.4 million people living with HIV in 2008 were women and children.

The Agenda was developed through extensive consultation with investigators, clinicians, civil society and UN agencies and was supported by an expert-led mapping exercise and literature review.

IAS Executive Director Robin Gorna said, “This agenda defines priority research needed to greatly improve our knowledge about and capacity to prevent and treat HIV in women and children. Implementation of this research agenda is key to closing these knowledge and service gaps and to saving women’s and children’s lives.”

The report identifies priority research questions within four broad categories: 1) clinical research on preventing mother-to-child transmission and pediatric treatment, 2) clinical research on women’s treatment issues; 3) operations research for women and 4) operations and implementation research related to stopping mother-to-child transmission.

To address these challenges, the report recommends increased investment in research, greatly expanding data sharing on HIV and women and children, as well as greater efforts to separate clinical data by gender.

The full research agenda on women and children is available online at www.iasociety.org/ilf.aspx.

Geneva, 24 September 2009 – The World Health Organization (WHO) and the Joint United Nations Programme on HIV/AIDS (UNAIDS) are optimistic about the results, announced today, of the largest ever HIV vaccine clinical trial held to date.

The study results, representing a significant scientific advance, are the first demonstration that a vaccine can prevent HIV infection in a general adult population and are of great importance.

The two UN agencies congratulate both the principal investigators, sponsors and the trial volunteers who have made this encouraging result possible.

The RV144 HIV vaccine study results, revealing a 31.2% vaccine efficacy in preventing HIV infections are characterized as modestly protective. However, these results have instilled new hope in the HIV vaccine research field and promise that a safe and highly effective HIV vaccine may become available  for  populations throughout the world who are most in need of such a vaccine. No vaccine safety issues were observed in the trial.

Much more work, though, has to be done by the principal investigators and a large group of international collaborators to analyse the trial data, understand the protective mechanism, determine the duration of protection, and map next steps. Licensure at this point in time may not be possible solely on the basis of this study's results, and it remains to be seen if the two specific vaccine components in this particular regimen would be applicable to other parts of the world with diverse host genetic backgrounds and different HIV subtypes driving different regional sub-epidemics. Once an HIV vaccine does become available, it will need to be universally accessible by all persons at risk.

In addition, early HIV vaccines with modest levels of efficacy would most likely have to be used as complementary tools in combination with strategies to promote changes in behavioural and social norms, promotion of correct and consistent condom use, access to safe injection equipment, as well as male circumcision.

The Phase III trial, involving 16 395 adult male and female volunteers in Thailand, was a test- of-concept of a novel HIV vaccine regimen with two different candidate vaccines developed by Sanofi-Pasteur and the non-profit organization Global Solutions for Infectious Diseases. The trial was performed by the Thai Ministry of Public Health, sponsored by the United States Army Surgeon General and received funding from the United States National Institute for Allergy and Infectious Diseases and the United States Army Medical Research and Materiel Command, Department of Defense. 

WHO and UNAIDS began supportive work for this trial 18 years ago, in 1991, when Thailand was recommended as one of the WHO-sponsored countries in preparation for HIV vaccine trials and the development of the National AIDS Vaccine Plan. In particular, WHO and UNAIDS through their HIV Vaccine Advisory Committee (VAC) provided continuous technical guidance and advice for review, approval and implementation of the RV144 trial protocol. In 2006, VAC performed an external evaluation of the trial examining various ethical and community-related issues: this evaluation showed that the trial was being conducted at the highest scientific and ethical standards and with active community participation.

Moreover, WHO and UNAIDS, in collaboration with partners, such as the Global HIV Vaccine Enterprise have jointly developed numerous policy documents relating to access to care and treatment for trial participants, design and purpose of test of concept HIV vaccine trials as well as scientific parameters.

WHO and UNAIDS will work with the global HIV stakeholder community to further understand and resolve a range of questions related to the potential introduction of an HIV vaccine of moderate protective efficacy. This includes additional, in-depth trials in different populations with diverse host and virus genetic backgrounds.

Until a highly effective HIV vaccine becomes available UNAIDS and WHO underline the importance of effective and proven HIV prevention methods for all people. A comprehensive HIV prevention package includes, but is not limited to, behavioural interventions to reduce sexual risk practices, including correct and consistent male and female condom use, early and effective treatment for sexually transmitted infections, male circumcision in high HIV prevalence settings, harm reduction for injecting drug users, post-exposure prophylaxis with antiretroviral drugs, and interventions to prevent HIV transmission in health care settings. 

Vincent was one of the 3,316 DART participants and is also one of the main characters of The DART Story, a newly launched documentary film. Credit: Medical Research Council

Having 12 children and a very old mother to support, Vincent, middle-aged Ugandan single father living with HIV, knows that his death would spell disaster for the whole family. “If I had died, where would these people go?” said VincentN perched on a stool with his legs outstretched

Fortunately, Vincent has survived. He said it is DART that has saved his life. DART, the Development of Antiretroviral therapy in Africa, is the largest HIV treatment trial ever carried out on the world’s second most-populous continent.

The DART trial has recently reached a remarkable finding in HIV treatment: that taking HIV treatment does not have to be accompanied by regular laboratory tests, at least for the first two years.

James Hakim, professor of the University of Zimbabwe Medical School and co-principal investigator of DART, said the health economists in the DART team who have analyzed the trial data have concluded that a third more people could be successfully treated for HIV in Africa if expensive lab tests weren’t used routinely. “The challenge now is for policy-makers to widen availability of ART,” said the professor.

Before, it was believed that a person on HIV treatment should have regular tests, including CD 4 cell counts, a measure of how well the body’s immune system, which is damaged by HIV, is working.

The DART results show that 87% of people receiving HIV treatment without routine blood test monitoring were still alive and well after five years, only 3 percentage points less than in the group that had routine blood test monitoring. This finding suggests that many more people living with HIV in Africa could receive treatment for the same amount of money that is currently spent on routine lab tests used to monitor the effects of antiretroviral therapy.

It could also lead to antiretroviral therapy being delivered safely and effectively by trained and supervised health workers in remote communities where routine laboratory tests are not available due to high costs or poor resources.

Professor Peter Mugyenyi of the Joint Clinical Research Centre in Uganda, also a DART co-principal investigator, agreed that governments now have evidence that expensive blood tests aren’t needed routinely for HIV treatment to be successful and safe. “It also means that treatment could be delivered locally as long as health care workers have the right training, support and supervision,” said Peter, “This could make a huge difference to people who live in remote areas that are many days walk from the nearest hospital or laboratory.”

According to UNAIDS estimates HIV treatment only reached a third of the 9.7 million people in need at the end of 2007. In Africa alone, around 4 million people urgently need antiretroviral therapy but the resources are limited.

The DART Story

Aiming at finding a safe, simple and more economical way of carrying out HIV treatment, the DART trial began six years ago when treatment for people living with HIV was just starting to become more widely available in Uganda and Zimbabwe.

Vincent was one of the 3,316 DART participants that had severe or advanced HIV infection while not having previously had any antiretroviral therapy. He is also one of the main characters of The DART Story, a newly launched documentary film narrated by Annie Katuregye. The narrator herself, whose husband died of AIDS-related illnesses seventeen years ago at the age of 34, joined the DART trial in Uganda in 2003.

Annie Katuregye joined the DART trial in Uganda in 2003 and is the narrator of the film The DART Story. Credit: Medical Research Council

Like all the other DART participants, Annie and Vincent
randomly allocated to one of two groups. People in the first group received antiretroviral therapy and their doctor was given the results of blood tests done every three months to check for drug side-effects and measure their CD4 cell count. People in the second group had the same antiretroviral treatment and the same blood tests done, but their doctors did not see CD4 count results and only saw the results of safety tests if they were seriously abnormal. People in both groups received free medical care and free diagnostic tests for episodes of illness throughout the trial.

Besides the only 3-percentage-point difference in survival, 78% of the people who survived in the first group had developed no new AIDS-related illnesses, compared with 72% in the second group. No difference in the occurrence of side effects caused by antiretroviral treatment was found between the two groups.

Moreover, irrespective of group, the survival rate in the DART trial is amongst the best reported from any trial, antiretroviral therapy programme or study in Africa. Historical comparisons, based on data from follow-up of similar patients in Uganda who did not have access to antiretroviral treatment make it clear that few of the DART participants would have been alive after five years without treatment.

Sponsored and funded by the UK Medical Research Council, the DART trial was collaboratively carried out by scientists and health care workers from Africa and the United Kingdom. With an original purpose of finding out whether the lab-based strategies used to deliver antiretroviral therapy to people with HIV infection in resource rich countries were essential in Africa, DART has hit its target.

Women and girls, who constitute half of all people living with HIV, are often underrepresented in biomedical HIV trials, particularly those assessing new treatment drugs or strategies.
Credit:UNAIDS/P.Virot

Women and girls, who constitute half of all people living with HIV, are often underrepresented in biomedical HIV trials, particularly those assessing new treatment drugs or strategies. When they are included, it may be in numbers that do not allow conclusions to be drawn about them. In spite of biological differences between men and women that can influence drug metabolism, research data may not be disaggregated, analyzed, and reported by sex.

One year ago today, a two-day meeting concluded which marked the beginning of the Women and HIV Trials initiative. This new forum opened a dialogue among peer academics, scientists and policymakers to challenge research norms underpinning the relative invisibility of women in clinical trial design, implementation, and reporting. The event was hosted by four partners, UNAIDS, the Global Coalition on Women and AIDS (GCWA), the International Centre for Research on Women (ICRW), and Tibotec.

A year on, the Women and HIV Trials initiative is generating interest at a global level. “The greatest success of the last year has been the simultaneous, multi-pronged approach to the challenge of the participation of women in HIV trials,” says Karen Manson of Tibotec, co-organizer of the original gathering.

“The Geneva meeting has catalysed many actions and initiatives - some directly the result of working groups that were established at the meeting but many others that are the indirect result of individuals being motivated to push for progress wherever possible.”

A number of strategic areas were identified during the initial 2007 consultation and formulated into an action plan implemented under the themes of: trial design, trial conduct, and reporting of results.

Trials designed with women in mind

In order to get an accurate picture of the participation of women in clinical trials, one of the activities of the last year has been to evaluate progress since 2000 in the proportion of women involved in later phase HIV clinical trials. The “score card” exercise found that publicly funded trials, such as the National Institute of Health (NIH)-sponsored trials in the USA, involve a significantly higher proportion of women participants than privately sponsored trials. The NIH commitment to adequate representation of women in their clinical trials follows on legislation in the USA on the inclusion of women and minorities in government sponsored trials.

“The progress seen in the US as a result of the Public Law revitalization act is indeed good news. However, clearly we still have far to go to meet these standards for HIV treatment trials” said Dr Sharon Walmsley, Professor of Medicine at the University of Toronto, Canada, who presented the results of this exercise at the International AIDS conference in Mexico in August 2008.

Trial recruitment and retention

Persuading women to join clinical trials can be difficult. Where women do enrol in trials, research shows that, due to a range of circumstances, they may drop out early. There is recognition that the involvement of community groups, including women’s groups, in trial design and implementation discussions can improve enrolment and retention. Reaching out to the places where women may gather or making existing trial sites more women-friendly, with child care and flexible schedules for instance, are ways to attract and retain women trial participants.

Trials run with needs of women met

Trial organizers have ethical responsibilities to participants. Clinic trial conduct can affect the health of research subjects. In HIV clinical trials, there is a duty to provide specific health care services, such as HIV prevention measures and access to antiretroviral treatment when it is indicated. For women participants, the health care package offered should also include sexual and reproductive health services, including regular pap smears for cervical cancer and screening for sexually transmitted infections.

“In defining the sexual and reproductive health care package to be provided to women in HIV trials, trial sponsors have the opportunity to do good and do well,” says Anna Forbes, Deputy Director, Global Campaign for Microbicides.

The Women and HIV Trials Initiative aims to stimulate people to think freshly about research practices.
Credit:UNAIDS/P.Virot

Forbes, a member of the “Women and HIV trials” initiative, is working with others to draw up guidance on the elements of a standardized sexual and reproductive health package for HIV trials. She underscored the important of providing acceptable contraceptive, reproductive, and sexual health care services—offered on-site when possible—to boost participant recruitment and retention and improve trial power by minimizing the rate of unintended pregnancies.

“Using trial resources to build sustainable access to such care after the trial is over (for example by training local public health staff and purchasing equipment that can be left for the community’s on-going use) also helps meet trials’ ethical responsibilities to reduce global disparities in access to health care whenever possible through trial conduct itself” says Forbes.

Trials that take into account the wider context of gender

The Women and HIV trials initiative has led to discussions on the role of clinical trials in exploring social factors, such as gender, that may explain differences in responses to an intervention being investigated. The International Center for Research on Women (ICRW) is taking the lead in promoting a social science perspective in trials.

At 2008 International AIDS Conference held in Mexico this summer, at which for the first time a number of satellites were held on “Women and HIV Trials”, ICRW launched a publication on the challenges of recruiting and retaining women in clinical trials.

Geeta Rao Gupta, the head of ICRW and a Steering Group member for the Women and HIV Trials initiative argues: “Clinical trials offer an unparalleled opportunity to collect and report social and behavioural data that can provide a more complete picture of the gender context of the HIV epidemic.”

Trials that report on sex differences

There are a number of differences in the way men’s and women’s bodies work. For example, body mass, hormonal cycles, and rates of metabolism are different by sex. However, when outcomes of trials come out in peer journals, these published scientific articles often do not report trial results by sex. This means that we remain blind to differences in drug levels and dosages in men and women.

The Women and HIV Trials Initiative aims to stimulate people to think freshly about research practices.

“When we set out to raise awareness and interest among a broad array of partners including researchers, community groups, national research sponsors, pharmaceutical companies, international regulatory authorities, and medical journal editors, we discovered there was a real surprise element,” notes UNAIDS Chief Scientific Adviser Catherine Hankins, a driving force behind the initiative.

“Many people told us that they had never thought about this issue before and had no idea that so little is known about sex differences in responses to drugs, including HIV medicines.”

To challenge this and pressure researchers designing trials, sponsors funding trials, and authors writing up trial results, the Women and HIV trials initiative is proposing a list of questions for the consideration of medical journal editors and peer reviewers as they assess trial manuscripts. They include two basic questions:

1. Is the study powered to draw conclusions about women? In simpler terms, are the numbers of women enrolled sufficient to allow for statistical analysis and the drawing of conclusions about possible sex differences?

2. Has the data been collected, disaggregated, analyzed, and reported by sex?

CONSORT (Consolidated Standards of Reporting Trials), whose guidelines are an essential reference for authors looking for guidance on how to write up their trial results for publication, has recently added a link on its website to the UNAIDS Women and HIV trials web page.

Next steps

Catherine Hankins reflects on the last year as a successful foundation for continued advocacy with a framework for action and the development of outreach materials - meeting report, brochure, score cards, website. “We have been creating momentum to change research norms so that women are better represented in HIV clinical trials and so that reporting of sex-specific results becomes routine,” she says. One of the important next steps for the Women and HIV Trials initiative, according to steering committee member Karen Manson, will be to demonstrate tangible results:

“Showing that more women are participating or having access to HIV clinical trials will be critical in breaking down the perception that it is an insurmountable challenge.”

Hankins sees a collaborative approach as the key to the consolidation and long-term success of this initiative:

“Our next step is to continue building a network of partners to advocate for placing women and adolescent girls at the centre of HIV clinical research.”

Through this, an impact on the wider epidemic is possible. As Director of the Global Coalition on Women and AIDS Kristan Schoultz states:  “If our response to AIDS isn’t working for women - and that includes our response from the clinical trials perspective - it’s basically not going to work at all.”

The meeting, sponsored by UNAIDS, the Global Coalition on Women and AIDS (GCWA), the International Center for Research on Women (ICRW) and the pharmaceutical company Tibotec, made recommendations in three core areas – policy and programmes, research and advocacy.

Health experts from international agencies, non-governmental and research organisations and universities as well as industry agreed on a series of steps aimed at ensuring that HIV trials and interventions are designed and implemented to reflect more closely the needs of women, who are increasingly affected by AIDS.

At the end of a two-day meeting at the UNAIDS Secretariat headquarters in Geneva, the group identified areas in which more research is required, including into the effect of sex differences on HIV interventions, and committed themselves to strengthening advocacy surrounding women and HIV trials amongst the donor community, governments and industry.

Describing the outcome as “heart warming”, Kathleen Cravero, Director of Crisis Prevention and Recovery at the United Nations Development Programme, said the issue of women and HIV was finally getting the attention it deserved. “I remember that not so long ago it was very hard to get anyone’s attention to that subject,” she told delegates.

Half of those living with HIV around the world are women, but the figure rises to over 60% in sub-Saharan Africa where infection rates are increasing amongst adolescents girls.

However, women are still under-represented in clinical trials for treatments and prevention strategies. The reasons are varied, and in part historical, but in developing countries they include cultural, social and economic factors, such as lack of empowerment for women.

This in turn requires that solutions to the problem go beyond strictly biomedical considerations to include structural issues, including poverty, delegates agreed.

The meeting, sponsored by UNAIDS, the Global Coalition on Women and AIDS (GCWA), the International Center for Research on Women (ICRW) and the pharmaceutical company Tibotec, made recommendations in three core areas – policy and programmes, research and advocacy.

The key themes identified were the overall issue of women’s involvement in trials, sex differences – gaps in knowledge, such as the varying effects of viral loads in men and women -- capacity building, opportunities for research, improving the dissemination of what is already known, adolescents, and sexual and reproductive health issues, including abortion and pregnancy in women living with HIV.

Half of those living with HIV around the world are women, but the figure rises to over 60% in sub-Saharan Africa where infection rates are increasing amongst adolescents girls.

On adolescent participation in trials, which is becoming a crucial issue given mounting infection rates in some parts of the world in this age-group, the group felt that more needed to be known about the benefits and drawbacks before clear recommendations could be made.

Targets for advocacy would include regulatory agencies, which would be encouraged to insist on the inclusion of more women in trials, research agencies and donors such as the Global Fund, medical journals and industry. The latter would be asked to set targets for the inclusion of women in testing.

Some future tasks were assigned amongst various organisations taking part in the meeting, attended by over 50 experts in various aspects of the AIDS response. The Global Coalition, for example, agreed to look into structural intervention issues, while UNAIDS will address the question of good participation practice (GPP).

It was suggested that the World Health Organisation, UNAIDS and the United Nations Population Fund (UNFPA) could call a special meeting to debate questions surrounding couples where one partner is HIV positive and the other not, often called sero-discordant couples, and issues such as fertility and pre-exposure prophylaxis.

The group, which will be issuing a full report on the outcome of the meeting, will also look into presenting a “report card” on HIV trials, assessing the degree to which they have included women.

All photo credit: UNAIDS/O.O'Hanlon

Read part 1 - Meeting ethical concerns over HIV trials
Read part 2 - The role of women in HIV trials
Read part 3 - Experts meet on women and HIV clinic trials
Read more on the meeting - Women and HIV research

Related information:

More on biomedical research

External links:

HIV Prevention Research: A Comprehensive Timeline

Publications:

Ethical considerations in biomedical HIV prevention trials (pdf, 750kb)
Good participatory practice - Guidelines for biomedical HIV prevention trials (pdf, 704 Kb)

Meeting at UNAIDS in Geneva, health experts said
that cultural and social barriers can still stop women
taking part in HIV trials in sufficient numbers, while
too little is known about the effects of biological
differences between the sexes in such areas as the
impact of HIV drugs.

Women and adolescent girls are on the frontline in the AIDS epidemic but getting them the special treatments, HIV prevention strategies and protection they need will require a varied, multi-disciplined response -- medical, social and economic, health specialists agreed.

Meeting at UNAIDS in Geneva, health experts from international agencies, non-governmental organisations (NGOs), research institutions and the private sector, said that cultural and social barriers can still stop women taking part in HIV trials in sufficient numbers, while too little is known about the effects of biological differences between the sexes in such areas as the impact of HIV drugs.

Winding up the first of two days of discussions on Monday 10 December, Kristan Schoultz, Director of the Global Coalition on Women and AIDS, said delegates had made a thorough review of the challenges and difficulties and the moment had come to start putting forward proposals for solutions.

“I think we have determined some of the challenges we face, (now) we need to tease out of this a way forward,” she said.

The route lay beyond a strict interpretation of the conference’s theme – “Making HIV Trials Work for Women and Girl Adolescents” -- and should include economic and social changes to address background factors such as poverty and empowerment.

“We need to highlight the difference between sex
and gender differences. Gender also brings in
social, cultural and economic issues as opposed to
the straight biological issues,” said Geeta Rao Gupta,
President, the International Center for Research on
Women (ICRW).

“We need to highlight the difference between sex and gender differences. Gender also brings in social, cultural and economic issues as opposed to the straight biological issues,” said Geeta Rao Gupta, President, the International Center for Research on Women (ICRW).

Although women account for some 50% of people infected with HIV worldwide, in sub-Saharan Africa the figure is around 60% and amongst some ethnic minorities in developed countries women also account for a disproportionate percentage. In parts of southern Africa, girl adolescents are some four times more likely to become infected with HIV than males of the same age.

For years after AIDS was first recognized in the early 1980s, medical research continued to be largely male orientated. Clinical trials involving women of child-bearing age had been banned in the United States in the late 1970s, in part because of the thalidomide scandals, and the restriction was not lifted until the early 1990s. In addition, the epidemic was initially thought largely a disease affecting men who had sex with men.

“The current research emphasis being put on microbicides for women is an illustration of the way in which priorities have changed,” said Roberta Jean Black, tropical microbicides team leader of the U.S. National Institutes of Health.

“The current research emphasis being put on
microbicides for women is an illustration of the way
in which priorities have changed,” said Roberta
Jean Black, tropical microbicides team leader of
the U.S. National Institutes of Health.

“Some of these inequalities simply represented misunderstandings of the disease and its evolution…We have responded successfully but the work is not done,” she added.

“The existing strategy was not designed with the percentage (of women) in mind. This is an iniquitous state of affairs,” declared Julie McHugh, company group chairman, virology, Tibotec.

More needs to be known about the progress of HIV in women.

“We are looking for answers for women. We now have women in menopause with HIV and we do not know anything about it,” said Heidi Nass, Director, Education and Policy Advocacy, Health HIV Care Program, University of Wisconsin. “We have seen the list (of things to do) a million times, it would be really nice to come out with action,” she added.

Gaps in understanding

There are many gaps in our understanding of HIV and how it evolves in women and the difference that gender can make, participants agreed. For example, CD4 tends to be higher in women, yet there appears to be no significant impact on the progress of the disease.

Most trials are not designed to detect sex
differences. “We are relying on safety trials from the
(rich, developed) north, and carried out on men,”
said Catherine Hankins, Chief Scientific Adviser to
UNAIDS.

But the difference can lead to delays in the timing of treatment for women. When it comes to mother-to-child-transmission (MTCT), this can have the unfortunate result that women who are not deemed sick, and are therefore not treated, are far more likely to infect their children than those who were inside the treatment threshold.

Most trials are not designed to detect sex differences. “We are relying on safety trials from the (rich, developed) north, and carried out on men,” said Catherine Hankins, Chief Scientific Adviser to UNAIDS.

There are also indications that some treatments have significant toxicity for women. Nevirapine, for example, can produce rashes and hepatic complaints. Toxicity can be one reason why women tend to abandon trials more often than men and is another area in which more research is needed.

Biologically different

Even if there are no side effects, it is possible that existing treatments may not be the best possible way of tackling HIV in women. Women are biologically different, so they need specific research.

Women in poorer countries can face a host of barriers to taking part in clinical trials. They may fear it will suggest that they are ill and lead to them being stigmatised, they could need permission from their partners or family – most people at risk are in long-term partnerships -- and they may not want to use contraception or they may fear for their future fertility.

Male circumcision provides no protection for women, although there could be secondary benefits for women, but more needs to be learned.

Difficult considerations

The whole question of trials for adolescents was thick with difficulties. Even a standard definition of what constitutes an adolescent is difficult to establish.

“Communities are very sensitive about involving young girls in trials for fear that they are promoting sexual activity,” said Gita Ramjee, Director, HIV/AIDS Lead Programme and HIV Prevention Research Unit, South African Medical Research Council.

Summing up the changes needed to help women and adolescent girls, Isabelle de Zoysa, senior adviser on HIV/AIDS at the World Health Organisation said: “We are looking how we move through gender unbiased, through gender sensitive to gender transforming.”

The conference, ‘Making HIV Trials Work for Women and Adolescent Girls’, takes place in Geneva on 10 – 11 December 2007. The meeting is co-sponsored by UNAIDS, the Global Coalition on Women and AIDS, the International Centre for Research on Women (ICRW), and Tibotec.

The conference, ‘Making HIV Trials Work for
Women and Adolescent Girls’, is co-sponsored by
UNAIDS, the Global Coalition on Women and AIDS,
the International Centre for Research on Women
(ICRW), and Tibotec.

Specialists on AIDS and women’s health are meeting in Geneva from December 10-11 to review the latest developments in research into preventing and treating HIV among women and adolescent girls from HIV infection, and to make recommendations on priorities and strategies.

The conference, ‘Making HIV Trials Work for Women and Adolescent Girls’, is co-sponsored by UNAIDS, the Global Coalition on Women and AIDS, the International Centre for Research on Women (ICRW), and Tibotec. The Global Coalition is an alliance of civil society groups, networks of women living with HIV and U.N. agencies; ICRW presses for women’s needs to be integrated into the design and implementation of programmes and policies; and Tibotec is an international pharmaceuticals company.

In the last of three articles focusing on HIV clinical trials ahead of the conference, senior representatives of the sponsoring organisations were asked about the challenges of getting women involved in sufficient numbers in HIV trials, the current state of research into prevention and treatment strategies for women and what they hoped the two-day meeting could achieve.

Catherine Hankins, Chief Scientific Adviser to UNAIDS, was asked why the conference was being held now?

Hankins: Although great strides have been made in recent years to include women as participants in HIV treatment and prevention trials in adequate numbers to draw conclusions relevant for them, challenges remain in recruitment, retention, study design, pregnancy, and meaningful engagement of women in trial design, conduct, and monitoring.  It is also clear that adolescent girls who are at very high risk of HIV exposure in some settings must participate in trials before the final results of efficacy in adults are known so that licensing of an effective product can proceed for both adolescents and adults at the same time. This conference focuses on the progress thus far, the challenges ahead, and solutions.

Question: Women make up an increasing percentage of people living with HIV, particularly in Africa. Do current international research programmes adequately reflect this?

Hankins: Yes, many of the Phase III efficacy trials underway for HIV prevention are taking place where incidence in women is highest – sub-Saharan Africa. These include microbicide trials, PrEP trials, trials of herpes simplex-2 suppression, and the vaccines trials.

Catherine Hankins: "Combination prevention is key.
This means increasing the choices that women and
girls have to use synergistically at different times of
their lives and in different circumstances to protect
themselves from HIV".

Question: So what are the most promising lines of investigation? Is enough being done to find effective prevention tools and treatment for women?

Hankins: The first to report (already in 2008) will be the Carraguard microbicide trial and the herpes simplex-2 suppression trials. A number of other trials are underway but we are in this for the long haul. The amazingly consistent compelling results of the male circumcision trials may not be repeated for other HIV prevention products at quite the same efficacy level. Combination prevention is key. This means increasing the choices that women and girls have to use synergistically at different times of their lives and in different circumstances to protect themselves from HIV.

Question: What do you see coming out of this conference?

Hankins: Strong steps toward defining a research agenda, recommendations for policy and programmatic actions, and an advocacy strategy.

Kristan Schoultz, Director of the Global Coalition on Women and AIDS, was asked how the situation regarding women and AIDS had evolved since the coalition, which was launched by UNAIDS in 2004, and what she felt the coalition had achieved?

Schoultz: GCWA - together with women's groups and partners across the globe – has worked to put women's issues high on the agenda of top international AIDS forums.  In 2006, U.N. Member states renewed and strengthened their commitments to scale up AIDS responses, and to address obstacles and barriers to access, particularly for women and girls.   The ways in which gender inequalities and gender dynamics affect  individual choices and behaviours are better understood and the issues facing women in a world of AIDS are more prominent in global and national advocacy. 

However, the situation of women and girls in the AIDS response continues to be a major concern.  We see rising rates of HIV infection among women in some regions and national AIDS responses have yet to sufficiently address the challenges and constraints women face in their everyday lives.  We need to see more concerted work towards legal frameworks which secure women's rights, more funding for concrete programmes that benefit women, and greater participation of women's organizations in national decisions on AIDS programmes and budgets.

Kristan Schoultz: "Trials may need to investigate
the socioeconomic position of women and offer
support to potential trial participants".

Schoultz: Within any trial, three issues must be addessed:  scientific justification, safety, and benefits for the community.  With respect to women, challenges all essentially relate to safety and benefit.  While women comprise a growing share of HIV infections every year, they are still underrepresented in HIV clinical trials which test the safety and efficacy of drugs.  Drugs tested only on men can be dangerous for women.  To get the gender-specific data that are needed, vaccine trials will need to enrol enough women and men to detect gender differences. Drugs work differently with female chemistry, and furthermore, drugs to help those conditions that emerge only in women may never be tested.  From a medical viewpoint, women do not reap as much from advances in medical technology. At present, more women are now being enrolled in clinical trials.  But many of the factors that affect women’s access to health services -- decision-making on health care, their social responsibilities, stigma associated with high-risk behavior, the threat of violence -- are the same barriers to their involvement in clinical trials.  Simple factors, such as physical access to the location of the study, availability of child or family care, inhibit their participation.  Trials may need to investigate the socioeconomic position of women and offer support to potential trial participants.

A huge challenge for women and adolescent girls is exercising their autonomy in participating in trials.  The process of enrollment, securing informed consent, and protecting them from the risks that can result from research participation is fraught with deeply embedded social norms which are largely biased towards males.  Gender-sensitive approaches are key when designing consent and recruitment procedures and risk-reduction interventions in HIV clinical trials.

Question: What contribution can this conference make?

Schoultz: UNAIDS and the Global Coalition on Women and AIDS are keen to have guidance on the links and complications of sex and gender on HIV treatments.  We hope this meeting will deepen our understanding of these intersections in various clinical research areas.  We hope that this meeting will help get HIV clinical trials done right for women.

Julie McHugh: "Twenty five years of this epidemic
has taught us that women and girls are at the heart
of any successful response to HIV".

Julie McHugh, Company Group Chairman, Tibotec, was asked about what are currently the most promising avenues of research in HIV anywhere and for her company in particular.

McHugh: There has been a renewed push across the AIDS field recently with new treatments coming to patients with high genetic barriers to resistance, and superior efficacy and tolerability.  This is an area that Tibotec is actively engaged in. Equally important are the development of new technologies and approaches that will simplify prevention and treatment approaches - in the fields of microbicides and Pre Exposure Prophylaxis particularly.  But the key challenge for anyone concerned about reversing the global AIDS epidemic is making sure we have genuine partnerships between communities, international agencies, NGOs and the private sector to bring these new advances to women and girls. Highlighting this urgent need is the rationale for us holding this forum in Geneva.

Question: Do you feel that enough is being invested in HIV research worldwide?

McHugh: On the one hand, you could say that there is never enough being invested or conducted in HIV research. However, signficant increases in resources and commitments have been made in recent years across the public and private sectors. What we have to do is to ensure that these resources are most effectively used - and again, this calls for more enlightened and long term partnerships between sectors.

McHugh: We want to raise awareness with policy makers and researchers of the importance of placing women and girls at the centre of HIV research. Twenty five years of this epidemic has taught us that women and girls are at the heart of any successful response to HIV.