Meta-Analysis Shows Women Are Under-Represented in HIV Clinical Trials

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Less than a quarter of people taking part in clinical trials for antiretroviral medications are women, potentially limiting the generalizability of findings, according to a systematic review published in the February 1 edition of the Journal of Acquired Immune Deficiency Syndromes.

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The authors said that gender differences in prevalence, incidence, symptoms, disease progression, and outcomes have been 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. Moreover gender differences in power, personal relationships, life experiences, and health literacy can influence people’s 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 severe in HIV.

The researchers searched for clinical trials of antiretroviral medications (of any phase) that were published in 8 major medical journals. In order to examine evolution over time, 3 time periods were selected: 1994-1997, 2001-2004, and 2008-2011.

In 387 separate studies with a total of 95,305 participants, only 23% of participants were female. The average proportion of women in each individual study was 19%. However, the average has improved over time -- from 9% in the mid-1990s to 22% more recently.

Research conducted in higher-income countries included fewer women. Studies funded by universities and charitable foundations recruited more women than pharmaceutical companies and public agencies. Although the U.S. National Institutes of Health (NIH) has been legally obligated since 1993 to only fund studies which will allow meaningful gender comparisons, in the third of the studies which the NIH partly funded only 20% of participants were women.

The researchers also examined 53 clinical trials of vaccines for HIV prevention. An average of 38% of participants were women. However, in 104 studies working towards a cure for HIV, the average rate of female participation was only 11%, with over a quarter of studies recruiting no women at all despite both sexes being eligible.

"Our study showed a persistent under-representation of women in HIV clinical trials," comment the authors. "Only with sufficient knowledge of sex and gender differences and similarities can optimal and evidence-based treatment, prevention, and care be delivered to both women and men living with or at risk for HIV."

They noted barriers limiting women’s participation in studies -- safety concerns, especially in relation to unborn children, requirements to use contraceptives while taking part, family and caregiving responsibilities making time commitments challenging, socio-economic inequalities, low education, and lack of understanding of what trials are.

The authors also point to a Phase 3 clinical trial in the U.S. (GRACE) which set out to address these barriers and in which 67% of participants were women (mostly women of color). Clinics with large numbers of female patients (primarily in the deep south) were selected as study sites even if they had less experience in running clinical trials. Study sites had quotas requiring more female than male participants, an experienced patient advocate worked with clinics on tailored recruitment strategies, outreach activities were conducted, and community groups were engaged. Enrollment criteria were broad and the reimbursement of transportation and childcare costs was publicized.

Nonetheless, the researchers running this trial reflected that they should have given as much attention to retention strategies as to initial recruitment -- individualized support to help women continue to engage with healthcare might have improved retention in this study.

2/12/16

References

MJ Curno, S Rossi, I Hodges-Mameletzis, 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 71(2):181-188. February 1, 2016.

R Falcon, DA Bridge, J Currier, 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 20(7):1043-1050. July 2011.