Each year, the U.S. Department of Health and Human Services Office on Women’s Health (OWH) brings together local, state, federal, and national organizations nationwide to raise awareness and show support for women and girls who are at risk for or have HIV. This year’s theme, You. Me. WE. Changing the face of HIV, focuses on the role that everyone can play in HIV prevention to improve the quality of HIV treatment and care for women and girls and eliminate HIV.

This occasion provides a special opportunity for the National Institutes of Health (NIH) Office of AIDS Research (OAR) to reflect on its role as the coordinator of the NIH HIV research portfolio and consider whether the NIH can take any additional steps to advance HIV/AIDS health research for women and girls.

Although HIV diagnoses among women in the United States have declined in recent years, HIV/AIDS remains a public health concern for women and girls; some racial and ethnic minority populations, such as women of color, are disproportionately affected.¹ Social determinants of health—such as stigma, poverty, medical mistrust, and fear of discrimination—often stand in the way of getting access to testing and treatment. 

At the end of 2018, across the United States and six dependent areas, 245,154 female adults and adolescents were living with diagnosed HIV infection: 58 percent were Black/African American; 20 percent were Hispanic/Latino, and 16 percent were white.²  HIV/AIDS poses a special risk for transgender women, who frequently experience discrimination and stigma and may have health care providers who lack in-depth knowledge of transgender issues. A systematic review and meta-analysis, reported in 2019, estimated that 14.1 percent of trans women in the United States have HIV.^3,4 

Promising research has yielded a number of breakthrough prevention options, and additional studies are underway to expand the suite of choice-based HIV prevention tools for women. As noted in my blogs HIV Prevention Forward: Choices for the Future and A Big Step Forward in the Expansion of HIV Prevention Choices for Women, these tools include long-acting injectable medication, an insertable vaginal ring, multipurpose prevention technologies, and new vaccination approaches. 

To ensure that the OAR is pursuing the best path forward with supporting the HIV/AIDS research agenda for all women and girls, I turned to my colleague Dr. Janine Austin Clayton, the Director of the NIH Office of Research on Women’s Health (ORWH). OAR and ORWH are located in the Division of Program Coordination, Planning, and Strategic Initiatives in the NIH Office of the Director. In her Director’s Message for Women’s History Month, Exceptional Individuals and Strong Collaborations Drive Advances in Women’s Health, Dr. Clayton describes activities that are essential to making progress in women’s health. I asked Dr. Clayton to narrow the focus and specifically discuss HIV/AIDS research. Here are some highlights from our conversation:

Dr. Goodenow: What unique concerns do girls and women face when it comes to HIV/AIDS?

Dr. Clayton: Globally, women (particularly young women) account for over half of HIV diagnoses; young women are twice as likely as young men to acquire HIV.⁵ Biological factors (components of the vaginal microbiome and sex differences in innate immunity)⁶ are compounded by social factors (stigma, social norms, and barriers to accessing sexual and reproductive health services) that create gendered inequalities and shape women’s and girls’ HIV risk.⁷ 

Risk for HIV exposure⁸ and potential downstream health outcomes^9,10 are influenced by many complex factors, particularly for women. Experiences of violence, economic opportunities (or lack thereof), and negotiating skills needed to achieve safe sexual encounters and needle cleaning with drug-use partners are all powerful influences.¹¹ Living at, near, or below the poverty line and, for women of color, the intersection of other issues of marginalization also come into play. For people of color, structural racism and systemic inequality diminish the ability to practice HIV risk-reduction strategies.^12,13 

In the United States, despite the overall declines in new diagnoses, Black women account for more than half of new HIV infections among women.¹⁴ Members of understudied, underrepresented, and underreported (U3) populations are diagnosed with HIV at disproportionately high rates. U3 groups include rural women;¹⁵ transgender women;¹⁶ women living at, near, or below the poverty line;¹⁷ and Black and Latina women.¹⁸ To help meet these distinctive research needs, the ORWH U3 Administrative Supplement Program targets interdisciplinary, transdisciplinary, and multidisciplinary research focused on the effects of sex and gender influences at the intersection of several social determinants of human health and illness. In addition to supplemental funding, educational resources for investigators—such as the recent webinar on mass incarceration, housing, and HIV/sexually transmitted infection risk—are important elements of the U3 program.  

Dr. Goodenow: Are you optimistic about the NIH research underway and the recent progress and findings?

Dr. Clayton: Even with known sex differences,⁶ women remain underrepresented and understudied in HIV research.¹⁹ However, I am proud of the role NIH has played in HIV/AIDS research and optimistic about recent advances. A few notable examples include the following:

• Research supported in part by NIH has found racial, ethnic, and geographic variability in women’s attitudes toward pre-exposure prophylaxis (PrEP), illuminating important areas for future research.^20,21 
• The AIDS Clinical Trials Group’s A5366, also known as the Moxie Study, was the first HIV cure study conducted entirely with women.²² 
• The HIV Prevention Trials Network’s study titled Integrating HIV Prevention, Gender-Affirmative Medical Care, and Peer Health Navigation to Prevent HIV Acquisition and HIV Transmission for Transgender Women in the Americas is proactively engaging with transgender women—a population that is disproportionately impacted by HIV and experiences unique barriers to prevention and care. 

Dr. Goodenow: In an ideal world, what should the HIV/AIDS prevention toolkit offer to girls and women who come from diverse backgrounds, traditions, and social circumstances?

Dr. Clayton: An ideal HIV prevention toolkit will provide women with choices of rigorously tested, evidence-based prevention modalities developed in partnership with women and girls from diverse backgrounds, traditions, and social circumstances. This toolkit should include woman-controlled options, such as vaginal rings, and pharmaceutical options, such as PrEP, as well as social and structural interventions aimed at the social determinants that put women at risk for HIV acquisition. Treatment as prevention (TasP) and the concept known as Undetectable = Untransmittable (U=U) will also play important roles in the HIV/AIDS prevention toolkit for girls and women.

Dr. Goodenow: Can you talk about the programs at NIH that are paving the way to address health disparities that put women at greater risk for HIV/AIDS and other health conditions?

Dr. Clayton: In all studies—and especially those in which disproportionately affected women are looked at—it is important that women be involved appropriately and equitably—as participants, as investigators, as community advisers, and at every point along the research continuum. 

As we mentioned earlier, in recognition of the need to attend to social determinants of health in prevention and intervention strategies and to attend to the contextual complexity of the lived experience of women, ORWH’s U3 program supports rigorous research on questions that are relevant to the health of women, including populations of women that experience health disparities or are otherwise socially or medically vulnerable.  

ORWH efforts support and complement those of the recently launched NIH UNITE initiative, which is focused on ending structural racism and promoting racial equity and inclusion in the health research field. Greater equity, diversity, and inclusion in health research expands the range of scientific perspectives and innovations that can accelerate progress to better the health of all, including the prevention, treatment, and—we hope—cure for HIV/AIDS. 

NIH policies on sex as a biological variable (SABV) and inclusion have distinct yet harmonious functions. The NIH SABV policy expects that SABV will be factored into research designs, analyses, and reporting in vertebrate animal and human studies. Such consideration increases rigor and transparency, which in turn improves the replicability and robustness of findings. Additionally, NIH requires that all clinical research applications address the inclusion of women, racial and ethnic minorities, and individuals of all ages and that NIH-defined Phase 3 clinical trials include plans related to the valid analysis of study results by sex/gender, race, and ethnicity. Investigators must provide annual updates on their progress in meeting enrollment goals, including providing the number of individuals enrolled in clinical studies, broken out by sex/gender, race, and ethnicity. NIH requires reporting of results of valid analyses by sex/gender and race/ethnicity in ClinicalTrials.gov for applicable NIH-defined Phase 3 Clinical Trials started after December 2017 per the 21st Century Cures Act. 

ORWH has a suite of free e-learning offerings to aid in the implementation of the policies, including Sex as a Biological Variable: A Primer, Bench to Bedside: Integrating Sex and Gender to Improve Human Health, and Introduction: Sex- and Gender-Related Differences in Health. The updated NIH Inclusion Outreach Toolkit is also available to better inform and enhance the engagement, recruitment, and retention of clinical trial participants. 

Dr. Goodenow: Looking at SABV to inform our understanding of HIV/AIDS, do you think we’re currently doing enough of this research at NIH to examine the impact of HIV/AIDS on women and girls?

Dr. Clayton: Until all applicable studies and clinical trials consider SABV and the data are disaggregated and reported by sex, more work needs to be done. That said, we see encouraging progress being made on multiple fronts in HIV/AIDS research. Here are just a few examples:

• Since 2017, ORWH has funded nine HIV-focused U3 supplements; we encourage the submission of proposals that explore the influence of HIV-related stigmas on U3 populations and communities (https://grants.nih.gov/grants/guide/notice-files/NOT-OD-20-156.html).
• Two recipients of the Intersection of Sex and Gender Influences on Health and Disease R01 are exploring sex differences in HIV.
• The National Institute of Allergy and Infectious Diseases recently awarded nine supplements to support research on reaching cisgender heterosexual women with PrEP. 
• On June 15, 2021, the Sex and Gender in Health and Disease scientific interest group will feature Alberto Bosque, Ph.D., discussing his research on the influence of sex hormones and hormonal replacement therapies on HIV cure strategies. (Registration is not required.) 

NIH continues to support and amplify research that examines HIV/AIDS in women and girls. Every woman living with or at risk for HIV needs and deserves the best research possible. NIH policies, resources for investigators, and targeted research funding work to help make this possible. 

Dr. Goodenow: Thank you, Janine, for this very informative conversation. 

The NIH OAR remains vigilant with efforts to advance the NIH HIV/AIDS research agenda to improve health outcomes for all people and will keep your input in mind as we push forward.

Maureen M. Goodenow, Ph.D.
NIH Associate Director for AIDS Research and
Director, NIH Office of AIDS Research

Janine Austin Clayton, M.D., FARVO
NIH Associate Director for Research on Women’s Health and
Director, NIH Office of Research on Women’s Health 

¹ Adimora AA, et al. HIV and women in the USA: what we know and where to go from here. The Lancet. 2021;397(10279): 1107–1115.

² Centers for Disease Control and Prevention. Diagnoses of HIV Infection in the United States and Dependent Areas, 2018: Women.

³ Becasen JS, et al. Estimating the prevalence of HIV and sexual behaviors among the U.S. transgender population: a systematic review and meta-analysis, 2006–2017. Am J Public Health (N Y). 2019;109(1): e1–e8.

⁴ Centers for Disease Control and Prevention. HIV and Transgender People. April 2019.

⁵ Geretti A, et al. Out of focus: tailoring the cascade of care to the needs of women living with HIV. HIV Medicine. 2017;18(S2): 3–17.

⁶ Scully EP. Sex differences in HIV infection. Curr HIV/AIDS Rep. 2018;15(2): 136–146.

⁷ The Lancet HIV. For the HIV epidemic to end so must gender inequality. The Lancet HIV. 2019;6(7): e411.

⁸ Bartz D, et al. Clinical advances in sex- and gender-informed medicine to improve the health of all: a review. JAMA Internal Medicine. 2020;180(4): 574–583.

⁹ Geter A, et al. Trends of racial and ethnic disparities in virologic suppression among women in the HIV Outpatient Study, USA, 2010–2015. PLoS One. 2018;13(1): e0189973.

¹⁰ Nwangwu-Ike, N, et al. Racial and ethnic differences in viral suppression among HIV-positive women in care. J Acquir Immune Defic Syndr. 2018;79(2): e56–e68.

¹¹ Li Y, et al. Intimate partner violence and HIV infection among women: a systematic review and meta-analysis. J Int AIDS Soc. 2014;17(1): 18845.

¹² Edwards AE, Collins CB Jr. Exploring the influence of social determinants on HIV risk behaviors and the potential application of structural interventions to prevent HIV in women. J Health Dispar Res Pract. 2014;7(Si2): 141–155.

¹³ Rao D, Andrasik MP, Lipira L. HIV stigma among black women in the United States: intersectionality, support, resilience. Am J Public Health. 2018;108(4): 446–448.

¹⁴ Bradley ELP, et al. Disparities in incidence of human immunodeficiency virus infection among black and white women—United States, 2010–2016. MMWR Morb Mortal Wkly Rep. 2019;68(18): 416–418.

¹⁵ Reif S, et al. State of HIV in the U.S. Deep South. J Community Health. 2017;42(5): 844–853.

¹⁶ Kalichman SC, et al. Transgender women and HIV-related health disparities: falling off the HIV treatment cascade. Sex Health. 2017;14(5): 469–476.

¹⁷ Breskin A, Adimora AA, Westreich D. Women and HIV in the United States. PLoS One. 2017;12(2): e0172367.

¹⁸ Adimora AA, Cole SR, Eron JJ. U.S. black women and human immunodeficiency virus prevention: time for new approaches to clinical trials. Clin Infect Dis. 2017;65(2): 324–327.

¹⁹ Curno MJ, 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. J Acquir Immune Defic Syndr. 2016;71(2): 181–188.

²⁰ Nydegger LA, Dickson-Gomez J, Ko TK. Structural and syndemic barriers to PrEP adoption among Black women at high risk for HIV: a qualitative exploration. Cult Health Sex. 2020 Mar 26: 1–15.

²¹ Willie TC, et al. Racial and ethnic differences in women’s HIV risk and attitudes towards pre-exposure prophylaxis (PrEP) in the context of the substance use, violence, and depression syndemic. AIDS Care. 2021;33(2): 219–228.

²² Dubé K, et al. Participant perspectives in an HIV cure-related trial conducted exclusively in women in the United States: results from AIDS Clinical Trials Group 5366. AIDS Res Hum Retroviruses. 2020;36(4): 268–282.