“Women are not small men” Tackling underrepresentation of women in HIV clinical studies

For National Women and Girls HIV/AIDS Awareness Day in the USA, Sprout Health Solutions wants to take this opportunity to bring attention to one of the health inequalities affecting women around the world – underrepresentation in clinical studies.  In this blog, we look at the barriers to recruitment, enrolment, and retention of women in HIV treatment and prevention trials and explore ways that these barriers are being addressed.

Women and girls with HIV

Women and girls account for 51% of people living with HIV globally.¹ Yet women have been underrepresented in clinical studies including trials of antiretroviral treatment (19% women), vaccine (38% women) and cure (11% women).²

The serious consequences of underrepresentation of women

Clinical trials are fundamental for evaluating the efficacy and safety of new drugs and interventions. There can be sex differences in how HIV drugs are absorbed in the body (pharmacokinetics), and in the response to the drug (pharmacodynamics).³ It is important to understand what these differences are and whether they result in variances in the safety or effectiveness of treatment.

Using behavioral science to understand and tackle underrepresentation

There are many reasons for the underrepresentation of women in HIV clinical studies. We looked to the literature to identify barriers to the enrolment and retention of women in clinical studies. We used the Capability, Opportunity, Motivation and Behavior (COM-B)⁵ theoretical model to categorize these and identify strategies to address them.

Attitudes to female participants are changing

Attitudes and behaviors concerning the involvement of women in clinical studies are changing. In the past, women were often excluded because of concerns about fluctuating hormones and pregnancy, and it was widely believed that women would have the same response to drugs as men.³ In the 1990s, the FDA implemented a series of guidance documents, lifting a ban on women of child-rearing potential from taking part in early phase research.³ The FDA also recommended that clinical studies should be representative of the population who would eventually be prescribed the drug; and stated that new drug applications should present safety and efficacy data for relevant subgroups including sex, race and age.

Efforts to improve representation of women in HIV clinical trials

Efforts to increase representation of women living with HIV in clinical studies have included many of the strategies outlined above, including targeted recruitment from HIV clinics where more women receive care, partnering with community organizations in the design and conduct of trials, addressing women’s concerns about clinical research and making it easier for them to participate.⁹ Using digital technology to enhance recruitment, engagement and retention along with data collection and analytics may also help some women to complete study visits and tasks.

Conclusion

Representation of women in HIV clinical studies is improving, but efforts to keep the dialogue in the public eye and maintain the momentum will be key to achieve equitable access to clinical studies. Ensuring that clinical studies are designed to recruit and retain a specific number of women will provide data of the effects of treatment in women and facilitate comparisons by sex. The meaningful involvement of women living with HIV in the design and implementation of research and the use of behavior science to identify and address barriers to participation will also help enhance recruitment and retention.

 References

1. World Health Organization https://www.who.int/gho/hiv/epidemic_status/cases_adults_women_children_text/en/. Accessed 10. March, 2021.

2. Curno MJ, Rossi S, Hodges-Mameletzis I, Johnston R, Price MA, Heidari S. A Systematic Review of the Inclusion (or Exclusion) of Women in HIV Research: From Clinical Studies of Antiretrovirals and Vaccines to Cure Strategies. J Acquir Immune Defic Syndr. 2016;71(2):181-188.

3. Liu KA, Mager NA. Women’s involvement in clinical trials: historical perspective and future implications. Pharm Pract (Granada). 2016;14(1):708.

4. Sengupta S, Strauss RP, Miles MS, Roman-Isler M, Banks B, Corbie-Smith G. A conceptual model exploring the relationship between HIV stigma and implementing HIV clinical trials in rural communities of North Carolina. N C Med J. 2010;71(2):113-122.

5. Michie S, Atkins, L., West, R. . The behaviour change wheel: A guide to designing interventions. London: Silverback; 2014.

6. Cargill VA, Stone VE. HIV/AIDS: a minority health issue. Med Clin North Am. 2005;89(4):895-912.

7. Inan OT, Tenaerts, P., Prindiville, S.A. et al. Digitizing clinical trials. npj Digit Med. 2020;3.

8. Stone VE, Mauch MY, Steger KA. Provider attitudes regarding participation of women and persons of color in AIDS clinical trials. J Acquir Immune Defic Syndr Hum Retrovirol. 1998;19(3):245-253.

9. 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. J Womens Health (Larchmt). 2011;20(7):1043-1050.

10. Pahus L, Suehs CM, Halimi L, et al. Patient distrust in pharmaceutical companies: an explanation for women under-representation in respiratory clinical trials? BMC Med Ethics. 2020;21(1):72.

11. Scharff DP, , Matthews, K. J., Jackson, P. et al. More than Tuskegee: Understanding mistrust about research participation. J Health Care Poor Underserved. 2010;21:879-897.

12. Sullivan PS, Khosropour CM, Luisi N, et al. Bias in online recruitment and retention of racial and ethnic minority men who have sex with men. J Med Internet Res. 2011;13(2):e38.

13. Clark LT, Watkins L, Pina IL, et al. Increasing Diversity in Clinical Trials: Overcoming Critical Barriers. Curr Probl Cardiol. 2019;44(5):148-172.

14. Barnett J, Aguilar S, Brittner M, Bonuck K. Recruiting and retaining low-income, multi-ethnic women into randomized controlled trials: successful strategies and staffing. Contemp Clin Trials. 2012;33(5):925-932.