5 October 2015
Women found under-represented in HIV clinical trials
Researchers have found that some conditions and diseases impact men and women differently, such as the following:
- cardiovascular disease
- autoimmune diseases (in which the immune system attacks the body)
The ways in which the above conditions and diseases affect men and women differently include the following:
- one gender may be more prone to developing certain conditions
- the course of illness
Researchers have also found that certain social factors can affect a person’s ability to access and use health services, such as the following:
- economic power
- health literacy
- life experience
In light of this information, studying the impact of gender on the prevention and treatment of illness is important.
A group of American and European researchers have conducted an extensive review of hundreds of published HIV clinical trials to assess the participation rate of women. They found that women are generally under-represented in such trials. They also underscore possible remedies.
The researchers scoured the biomedical literature for clinical trial information regarding studies in three subject areas:
- anti-HIV drugs
- vaccines to prevent HIV infection
- HIV cure research
For each subject area they searched within particular periods of time, as follows:
- 1994 to 1997
- 2001 to 2004
- 2008 to 2011
Vaccines to prevent HIV infection
- 2001 to 2012
HIV cure research
- 1995 to 2012
Results—Clinical trials of anti-HIV drugs
Researchers reviewed data from 387 clinical trials that had enrolled 95,305 participants collectively. In total, about 23% of participants (22,098) were women. However, the proportion of women within each clinical trial varied considerably from 0% to 95%, with an average of 19%.
The researchers also found that 11 clinical trials only recruited males, even though there was no formal restriction based on gender.
Over the periods of time reviewed, researchers found that the proportion of women enrolled in clinical trials increased significantly, as follows:
- 1994 to 1997 – 9% of participants were women
- 2001 to 2004 – 18% of participants were women
- 2008 to 2011 – 22% of participants were women
Most (81%) clinical trials of anti-HIV drugs were conducted in high-income countries. The researchers found that studies conducted in low- and middle-income countries were more likely to have a greater proportion of women—about 50%—compared to clinical trials held in high-income countries, which had about 18% of female participants.
Results—Vaccines to prevent HIV
For this subject area, researchers focused on 53 clinical trials with an overall total of 33,073 participants. Among these participants, 31% (10,303) were women. The proportion of women in each clinical trial varied considerably, from a low of 6% to a high of 67%, with an average figure of 38%.
As with the analysis of trials of anti-HIV drugs, researchers found that there was a significant increase in the participation of women over time in HIV vaccine studies. Furthermore, clinical trials of HIV preventive vaccines that were conducted in low-income countries (a total of four trials) had proportionally less women (23%) than similar trials held in high-income countries (a total of 38), where the female participation rate reached almost 40%.
Results—HIV cure research
Researchers focused on 104 studies with a total of 15,655 participants, of whom 3,356 (about 21%) were women. The proportion of women enrolled in these studies also varied considerably from one study to another—from 0% to 89% (with an average of 11% female participation). Strikingly, 29 studies (28%) that engaged in cure research did not enroll any women.
The vast majority of cure research studies (94) were held in high-income countries. Studies conducted in low- and middle-income countries were more likely to have more women (an average of 22%) compared to trials held solely in high-income countries, where the participation of women was about 10%.
Bear in mind
1. Although the proportion of women enrolled in HIV clinical trials has generally been increasing, it is still too low.
2. The proportion of female participants was lowest in HIV cure clinical trials, about 11%. The researchers stated that cure research is “an emerging line of enquiry, suggesting that cure studies are more experimental in nature, which in turn may explain—though not justify—the low numbers of women.”
3. Other analyses of gender done over the past 15 years have also found low proportions of women enrolled in HIV clinical trials.
4. Studies concerning anti-HIV drugs or cure research done in low- and middle-income countries generally had greater proportions of women participating than studies done in high-income countries. In contrast, HIV vaccine studies had the opposite distribution of women.
The researchers suspect that this distribution of gender in the different subject areas may reflect the epidemiology of HIV; certain populations are likely to be infected in different regions. For instance, in high-income countries HIV disproportionally affects gay and bisexual men, while in many parts of sub-Saharan Africa HIV is generally more common among heterosexuals and evenly distributed between genders. The researchers stated that this distribution of HIV between genders in different regions and the gender imbalance in many clinical trials “may reflect the ease of the motivation of men and women to participate in clinical studies with [anti-HIV drugs] and/or curative strategies in their respective countries/regions.”
Specific barriers to women’s enrollment
Researchers who have studied women’s participation in clinical trials in other health conditions have found that barriers to female participation in clinical trials may be related to the following:
- poor socioeconomic conditions
- gender inequality
- low levels of education
The research team that performed the present analysis of gender and HIV clinical trials advanced the following reasons that likely hinder women’s participation in such trials:
- not understanding what clinical trials are about
- lack of awareness of clinical trial recruitment
- misunderstanding the required time commitment
- cost issues (such as transportation, childcare)
- concerns about pregnancy and the potential that the drugs used in a clinical trial may affect the health of the fetus
One HIV clinical trial with a large proportion of women that was conducted in the recent era is called Grace. This trial involved the use of darunavir (Prezista)-based anti-HIV therapy (ART) and was sponsored by the Janssen pharmaceutical company. When they designed Grace, researchers took into account potential barriers to women’s participation. Specific study sites (clinics) were selected and there was an effort to engage with female community members and advisors. The planning that went into Grace could provide useful ideas for future clinical HIV trials.
Another study called Waves, sponsored by Gilead Sciences, was able to recruit and retain more than 500 HIV-positive women for its comparison of different ART regimens.
A call to action
The researchers closed their report with the following statement aimed at scientists, funding agencies and biomedical journals:
“All research stakeholders need to be actively engaged in order to achieve progress towards satisfactory gender balance and meaningful sex- and gender-based analysis in research. In their infancy, trials must be designed with this goal in mind, including recruitment quotas and context-specific planning. Reviewers of funding applications and publications should ensure that adequate female representation has been addressed. Journal editors should enact a strict policy for reporting female representation and, lastly, funding bodies should require and enforce adequate female representation.”
Clinical trials – what you need to know – Canadian HIV Trials Network (CTN) and the Canadian AIDS Society (CAS)
—Sean R. Hosein
- Curno MJ, Rossi S, Hodges-Mameletzis I, et al. A systematic review of the inclusion (or exclusion) of women in HIV research: from clinical studies of antiretrovirals and vaccines to cure strategies. Journal of Acquired Immune Deficiency Syndromes. 2015; in press.
- Falcon R, Bridge DA, Currier J, et al. Recruitment and retention of diverse populations in antiretroviral clinical trials: practical applications from the gender, race and clinical experience study. Journal of Women’s Health. 2011 Jul;20(7):1043-50.
- Squires K, Kityo C, Hodder S, et al. Elvitegravir (EVG)/cobicistat (COBI)/emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) is superior to ritonavir (RTV) boosted atazanavir (ATV) plus FTC/TDF in treatment naïve women with HIV-1 infection (WAVES Study). In: Program and Abstracts of the 8th IAS Conference on HIV Pathogenesis, Treatment and Prevention, 19-22 July 2015. Abstract MOLBPE08.