Fewer than a quarter of the population participating in clinical trials of antiretroviral drugs are women, potentially limiting the possibility of generalization of findings, according to a systematic review published in the February 1 Journal of acquired immunodeficiency syndromes.
The authors state that gender differences in prevalence, incidence, symptoms, and disease progression as well as outcomes were noted across a range of diseases. Differences in pharmacokinetics (how drugs are absorbed and distributed in the body) and pharmacodynamics (the effect of a drug on the body) can result in differences in side effects and response to treatment.
In addition gender differences in power, personal relationships, life experiences and systemic learning in the health field can influence people at risk of infection, health seeking behavior and use of health services.
Limited participation of women is a concern for clinical trials across a wide range of disease areas, but the problem appears to be particularly acute in HIV patients.
The researchers evaluated the clinical trials of antiretroviral drugs (from any stage) that were published in eight major medical journals. In order to examine evolution over time, three time periods were selected: 1994-1997, 2001-2004, and 2008-2011.
In 387 separate studies with 95,305 participants, only 23% of the participants were female. The mean proportion in each individual study was 19%. The average has improved over time - from 9% in the mid-nineties to 22% more recently.
Research conducted in higher income countries has a smaller number of female subjects as well as female gender involved in these studies.
Studies funded by universities and charitable foundations have recruited more women than pharmaceutical companies and public bodies. Although the US National Institutes of Health have been legally obliged since 1993 to fund only studies that will allow for gender comparisons, significantly, the third of the studies funded by them in part had only 20% of female participants.
The researchers also examined 53 clinical trials of vaccines for HIV prevention. An average of 38% of the participants were women. However in 104 studies work towards a cure for HIV, the average female participation rate was only 11%, with more than a quarter of studies not recruiting women at all despite both sexes being eligible.
"Our study showed a persistent underrepresentation of women in HIV clinical trials," the authors write. "Only with sufficient knowledge of sex and gender, differences and similarities can evidence-based treatment, prevention, care and delivery be delivered to both men and women living with or at risk for HIV in a optimal way."
They note barriers that limit women's participation in studies - safety concerns especially regarding unborn children, requirements for contraceptive use while taking part in the study, the need to take care of the family and take care of responsibilities honoring time commitments is challenging, and socioeconomic inequalities, as well as important, low schooling and lack of understanding of what the studies represent.
The authors also point to a Phase III clinical trial in the United States that has been defined to address these barriers, where 67% of the participants were women (mainly women of color). Clinics with a large number of female patients (mainly in the deep South) were selected as study sites, even if they had less experience of performing clinical trials; study sites had quotas requiring more female subjects than male participants; an experienced patient lawyer worked with clinics on personalized recruitment strategies; awareness activities were conducted; community groups were contracted with the reimbursement of transportation costs and host was publicized and registration criteria; were ample.
However, those who conducted this trial reflected that they should have given as much attention to retention strategies as to initial recruitment - personalized support to help women continue to collaborate with their health may have better retention in this study.
Translated by Cláudio Souza, from the original by Roger Pebody in Women under-represented in HIV clinical trials in 12 February 2016