HIV-positive women in clinical trials: A gap in the facts

Sharon L Walmsley is one of a group of female physicians, experts and patient advocates who together set up Women for Positive Action, an organisation that campaigns for better inclusion of women’s needs into HIV research and care. Here she argues that women’s under-representation in clinical trials contributes to ignorance of issues affecting women, and how to address them.

Women currently represent half of all people who live with HIV globally, and that proportion is increasing in some world regions. Yet women are considerably under-represented in HIV clinical trials: since 2000, only 20% of participants in clinical trials of antiretroviral therapy (ART) were women and the proportion has declined in the past 8 years.¹

This leaves a significant gap in understanding of women and HIV, which is discussed in a recently published opinion piece by Women for Positive Action.²

The risk to the foetus of maternal medication in pregnancy, exemplified by thalidomide in the 1950s and 1960s, has dominated discussions about the enrolment of women into clinical trials. In the United States, the Food and Drug Administration forbade women from participating during the early stages of pregnancy following this tragedy. The repercussions meant that many women were precluded from clinical trials.

More recently, the need to include more women in clinical trials has been given greater attention in order to have sample sizes large enough to take participant’s sex into account. However, it is clear that the balance has not yet been achieved.

Low female representation in clinical trials over the past ten years is significant not only because half of all people living with HIV are female, but also because women may respond differently to both the disease and ART than men do. For example, women have been consistently shown to have lower viral loads than men at similar stages of HIV infection, most markedly early on, following HIV seroconversion.³ However, the cause and significance of viral load differences remain unclear.

In addition, it has been suggested that women may respond better to ART than men: in one study, women had better CD4-count responses to therapy and lower death rates, though they experienced more drug-related side-effects.⁴ However, existing studies don't provide a clear picture about the use of ART among women.

Women’s physical make-up is different to men’s: they have a lower body mass, higher body-fat content and hormonal differences. Adverse effects and the ability to tolerate certain antiretroviral drugs may differ in women. Birth control pills, hormone replacement therapy and pregnancy could also alter the effects of HIV medications. Without data investigating the impact of these on treatment in women with HIV, potential improvements to the lives of millions of women are impeded.

Some HIV clinical trials have been successful in increasing women’s participation. For example, 38% of participants in the STEP trial, which aimed to find a preventive HIV vaccine, were women.  

The GRACE Study⁵ was specifically designed to assess sex-based differences in the efficacy and safety of darunavir boosted with ritonavir (DRV/r), To achieve the recruitment goal of 420 patients (approximately 70% female), each study site was required to enrol three women before enrolling a man. Of the 429 people living with HIV enrolled, 287 were women.

Women living with HIV must also understand the importance of them volunteering to participate in clinical trials.

What we learn from women today can be applied to women's care in the future.

Professor Margaret Johnson, Royal Free Hospital, London

It reported similar treatment response rates between men and women, but over a third of women dropped out of the trial compared with under a quarter of men; some discontinuations may represent challenges unique to women in clinical trials. For future studies, the authors highlighted the importance of addressing the unique needs of women during the screening process and throughout, to optimise study retention

According to the founder and Chair of The Well Project, Dawn Averitt Bridge, “GRACE sets a new standard for how future HIV studies should be conducted, as we now know that treatment-experienced women…can and will successfully participate in clinical trials if the studies are designed and supported in the right way.”

Given these recent successes, how can we continue to ensure that more women are included in HIV clinical trials? Researchers, physicians and clinical trial sponsors all need to take action in order to address the imbalance.

Professor Jane Anderson, HIV consultant physician at Homerton University Hospital, London, elaborates: “The under-representation of women in HIV-related clinical trials falls into three main areas: the study design and protocol, increasing the participation of women in trials and raising awareness across the HIV field that more studies and data analysis is needed in women.”

Clinical researchers need to ensure equal sex representation in the early stages of drug development. At the same time, clinical trials should be designed to give meaningful data on sex-related differences and remove unfair barriers to female participation. For example, the provision of childcare and other social support can often be seen as unaffordable or unnecessary, but these can be critical to women’s participation.

Including women in the planning stages of clinical trials will allow these issues to be raised. Furthermore, physicians should work closely with investigators to support the inclusion of women, and clinical trial sponsors should find ways to collaborate with centres and investigators that treat a high proportion of HIV-positive women.

“More women should be involved in the planning and implementation of studies to ensure the needs of female participants are considered,” notes Professor Margaret Johnson, consultant physician at London’s Royal Free Hospital. “Women living with HIV must also understand the importance of them volunteering to participate in clinical trials. What we learn from women today can be applied to women’s care in the future.”

Beyond researchers and doctors, the national and supranational regulatory authorities can have a positive effect on women’s representation in clinical trials. Journals that publish HIV research and conference organisers also play significant roles in drawing attention to the importance of the issue: editors and organisers should encourage submissions focusing on women and include female health specialists on editorial and conference boards.

Improving women’s health is not only a women’s issue. As the GRACE study in the United States proved, by learning more about how women respond to HIV treatments and by improving their total quality of care, we can not only improve their quality of life but also that of their partners, children and communities.

Winnie Ssanyu-Sseruma of Christian Aid believes that “Encouraging the participation of community representatives in the planning and implementation of trials is vital. Community involvement at all levels is essential if we are to enrol more women in clinical trials.”

Leaders in medicine, research, public health and communities can improve the lives of women living with HIV, but specific data on the effects of treatments will be essential. Together, we need to ensure that women around the world can benefit from the knowledge gained through HIV clinical trials.

Further information

Women for Positive Action is a global initiative established in response to the need to address specific concerns of women living and working with HIV. The group is made up of healthcare professionals, women living with HIV, and community group representatives from across Canada, Europe and Latin America.

Women for Positive Action aims to empower, educate and support women with HIV and the professionals and community advocates/leaders involved in their treatment. The group explores issues facing women with HIV and provides meaningful education-based support to respond to these needs and to contribute towards an enhanced quality of life for women with HIV. For further information, please visit www.womenforpositiveaction.org.

Women for Positive Action acknowledge the contribution of Winnie Ssanyu-Sseruma in the preparation of this article.