Increasing the meaningful involvement of women in HIV cure-related research: a qualitative interview study in the United States

Figures & data

Table 1. IRB-approved interview guide—women’s involvement in HIV cure-related research (United States, 2022).

Introduction First, thank you so much for your time. What is your current position and involvement in HIV-related research? What about research focused on women? Can you please describe your involvement, if any, in HIV (including cure)-related research? Inclusion of Women in HIV (Including Cure) Clinical Research We’d love to hear your thoughts on how we should decide who is included in a HIV-related clinical trials. What are the primary requirements? How should we decide how many women versus men should be included? Can you please describe the common challenges to including women in HIV-related cure research? Meaningful Participation of Women in HIV (Including Cure) Research Can you think of clinical trial examples in HIV research that were fairly equitable by sex and gender? What needs to be done to facilitate more equitable inclusion of women in trials? Do you think scientific data should be disaggregated by sex and gender? Why/why not? We’d love to hear your thoughts on women’s willingness to test risky interventions? What might be some of the considerations? Do you think women would be willing to undergo invasive study procedures? What considerations should be taken about including people of child-bearing age? Women and HIV Treatment Interruptions Can you please share your thoughts on whether women would be willing to interrupt HIV treatment to help advance HIV cure research? What might be the primary considerations for women undergoing HIV treatment interruptions? What safeguards should be in place for women undergoing HIV treatment interruptions? Additional Considerations What responsibility should clinical research sites have in terms of providing additional assistance to women participating in clinical trials? Can you please share your thoughts on what additional factors should be considered during HIV cure-related trials involving women? What considerations should be taken with transgender and gender-diverse individuals in HIV cure-related research? Wrap Up and Closing Is there anything that you would like to add or things we should know that we haven’t yet discussed? Is there anyone else you can think of who we should try and speak with about this topic? Thank you for taking the time to answer these questions. Your participation greatly contributes to our understanding of how we can best engage women in HIV related clinical research. Please feel free to contact us at any time if you have any questions about this interview or the research project.

Table 2. Self-identified demographic characteristics of key participant interview participants (United States, 2022).

Participant ID number	Sex assigned at birth	Gender	Race	Ethnicity	Participant type
01	F	W	White/Caucasian	Non-Latinx	Biomedical Researcher
02	F	W	Black/African American	Non-Latinx	Community Member
03	F	W	White/Caucasian	Non-Latinx	Community Member
04	F	W	White/Caucasian	Latina	Community Member
05	F	W	White/Caucasian	Non-Latinx	Biomedical Researcher
06	F	W	White/Caucasian	Non-Latinx	Biomedical Researcher
07	F	W	White/Caucasian	Non-Latinx	Biomedical Researcher
08	F	W	Black/African American	Non-Latinx	Community Member
09	F	W	White/Caucasian	Non-Latinx	Community Member
10	F	W	White/Caucasian	Non-Latinx	Community Member
11	F	W	Black/African American	Non-Latinx	Community Member
12	M	F	Asian	Non-Latinx	Community Member
13	F	W	White/Caucasian	Non-Latinx	Community Member
14	F	W	African	Non-Latinx	Community Member
15	F	W	Black/African American	Non-Latinx	Community Member
15	M	M	White/Caucasian	Non-Latinx	Community Member
17	F	W	Black/African American	Non-Latinx	Community Member
18	F	W	Black/African American	Non-Latinx	Community Member
19	F	W	White/Caucasian	Non-Latinx	Biomedical Researcher
20	F	W	Black/African American	Non-Latinx	Community Member
21	F	W	Asian	Non-Latinx	Biomedical Researcher
22	F	W	White/Caucasian	Non-Latinx	Biomedical Researcher
23	F	W	White/Caucasian	Non-Latinx	Biomedical Researcher
24	F	W	Asian	Non-Latinx	Biomedical Researcher
25	F	W	White/Caucasian	Non-Latinx	Community Member
26	F	W	Eur-Asian	Non-Latinx	Biomedical Researcher
27	F	W	White/Caucasian	Non-Latinx	Biomedical Researcher

F = Female; M = Male or Man; W = Woman.

Table 3. Select quotes—meaningful women’s involvement in HIV cure-related research (United States, 2022).

Themes	Sub-Themes	Participant number	Participant type	Quotations
Inclusion of Women in HIV (Including Cure) Clinical Research
Perceptions on Inclusion of Women in HIV Clinical Research
Need to ensure broad representation by sex and gender		27	Biomedical Researcher	Honestly, we’ve known for a long time that physiologically, men and women and people of different genders have different immune system, different physiologic biology of HIV in terms of their virus host interactions, they also have different socio-economic realities… So it’s extremely important for us to involve many different types of people, including people of different sexes and genders.
Need clear definition around sex or gender		12	Community Member	Most of the research today is still done with binary gender in mind, male or female, and really doesn’t capture some of the gender identity and expressions on the spectrum. I think that it’s really important, if we are looking at these demographic informations, that we reflect accurate gender identity or gender expressions of participants. So in addition to transgender women, there are transgender men. Also, there are some who identify as non-binary, and they don’t consider themselves on the spectrum
Common Challenges to Including Women in HIV Cure Clinical Research
Engagement and outreach-level challenges	Paternalism	19	Biostatistician	There’s a paternalism… And so women are never approached and not asked… the theme I have heard over the years when having the wonderful opportunity to hear members of the community… is, "I was never asked, I was never approached, I was never aware."
Meaningful Participation of Women in HIV (Including Cure) Research
Successful and Less Successful Clinical Trial Examples
Successful examples	GRACE study	03	Community Member	The GRACE study, done almost 15 years ago now, really demonstrated that it was possible to recruit women in the US in a treatment study. GRACE stood for Gender, Race, and Clinical Experience, which really resonated and meant something to women—to us. One of the amazing things about the GRACE study is that it enrolled nearly 70% women and 87% people of color. It was pretty astonishing in the US at the time and it really dispelled the myth that enrolling women domestically wasn’t possible.
Less successful examples	DESCOVY pre-exposure prophylaxis trial	18	Community Member	Let’s just be real and talk about what a tragic mistake and bad decision not including cisgender women in the DESCOVY trial was, right? … Now there’s a whole new trial rolling out that is inclusive, actually has a separate track specifically for cis women, and had to have the inclusion of these women from the beginning, from before the protocol was finalized, before the protocol was written, submitted, and approved for study. All of that had to be done creating a whole different way of engaging the community so that there was accountability on top of the advisory work that’s supposed to be done. And having more of a partner approach to how this study is going to roll out is what has happened as a result of not including women in the first place.
Steps to Facilitate More Equitable Participation of Women
Protocol-level solutions	Socio-behavioral and mental health component	18	Community Member	It has to have a very robust social, behavioral and mental health approach to the overall enterprise for cure research. That it cannot just be about cells and drugs in bodies, that it really has to be understanding what cure means, how it might play out.
Institution-level solutions	Representation at clinic level	01	Biomedical Researcher	Representation matters. If we have a clinic where 90% of the doctor are white men, women will not be motivated to even show up and enroll. Having representation at every stage from the nurse to the doctor will be important.
Disaggregating Scientific Data by Sex and Gender
Frequent mis-categorizations and misclassification by gender		16	Community Member	People report a category of trans or non-binary, which, it’s not disaggregating transgender men versus women. It’s not disaggregating transgender or non-binary people. It’s just kind of lumping them together into a category, which is not ideal, or that doesn’t seem ideal to me. It would be far better to actually identify transgender men and women and non-binary people separately… One uses the term transgender spectrum. Just sort of lack of standardization of terminology.
Testing Interventions in Women
Sex is an important variable		22	Biomedical Researcher	The data broadly indicates that sex is one host factor that will have to be considered, and it has top level implications for a bunch of interventions, including histone modification and latency reversal agents, which are impacted by estrogen in vitro potently, including anti-exhaustion therapies like anti-PD1 [programmed-death-1], which in the cancer literature have been shown to have sex differential efficacy, so one would predict that they might have the same difference in efficacy here. Then vaccines, which in that case, maybe females will do better, because female responses to vaccination are generally somewhat more robust. For block and lock, we really don’t have much data… if it’s silencing and it’s histone modification or chromatin modification, there are lots of differences in how those are managed on the cellular level between male cells and female cells.
Willingness to Undergo Invasive Procedures (e.g. Biopsies)
Women willing to undergo invasive procedures	Adequate compensation needed	02	Community Member	So one thing that I've learned about the HIV community is that the HIV community is willing to be involved in research to help the next person, right? If it’s going to help the next person down the line, then I'm willing to do it. But presentation matters, compensation matters. I'm definitely not going to let you do a biopsy for a gift card. You can forget that. But if it’s something that’s going to make a difference for my family that I'm trying to take care of, then yes, I would consider it. So it depends on the woman. It depends on how the information is presented and it depends on the compensation and that’s just as real as I know how to be about it.
Deterrents	Prior physical abuse	14	Community Member	She cannot have someone touching her body when she’s asleep. Most of this is not even to do with the fear of that, but a lot of women have had abuses. They’ve had rape, they’ve been sexually violated and for some of them, these are triggers. These are issues that you need to talk about.
People of Child-Bearing Potential
Double barrier of contraception acting as a deterrent		09	Community Member	One thing that always bothers me is when they request two forms of birth control. I think that’s a little overboard for a lot of people. That’s just not something that’s going to happen when you’re married and on birth control… I'm not going to go through the extra step and ask my partner to also put on a condom, because in addition to everything that we’re already doing, I have to have two forms of birth control for this study… I don’t have an issue with one form of birth control because I understand that you don’t want anything occurring to the baby, but when they go to the two forms of birth control, that always irritates me a bit.
Women and HIV Treatment Interruptions
Women’s Willingness to Interrupt HIV Treatment
Willing to undergo HIV treatment interruption	Skipping pills occasionally	02	Community Member	I actually was looking into a treatment interruption study… It doesn’t have as much to do with the cure research as it does with me personally, which is that I've been skipping pills anyway… I've been skipping just because of life. Life is doing what life is doing right now. And so for me, my thought was, "If I'm already missing medication, maybe I can get involved in this treatment interruption study." It benefits me because then I don’t feel guilty about skipping my meds, but then it also benefits science because I'm participating in this research. So that again is how is it being presented, right? Or how are you asking me if I'm interested in this and are you listening to my reasons for why I want to be involved? … So that way, if I know that you’re going to be checking my viral load and you’re going to be watching out for what’s going on.
Not willing to undergo HIV treatment interruption	Ritualistic relationship with ART pills	10	Community Member	I have to say, my relationship to my pills may be unusual in that I love my pills. I've had blessing ceremonies for my pills. When I take my pills, I see my friends in a circle, praying for me and my pills. So it’s like I have a very consciously chosen choreographed relationship to my pills. And that’s very unusual. Most people’s relationship to their pills is… “This is a daily reminder that I'm stigmatized. This is a daily reminder that there’s something wrong with me."
Enrollment of Women in ATI-Inclusive Trials
Need to understand partnership dynamics		02	Community Member	I definitely feel like if you’re going to involve a woman in treatment interruption, then you need to make sure what’s her current partnership status. Does she have a partner? Is that partner HIV positive or negative? Is that partner on PrEP? What are their thoughts around U = U [Undetectable = Untransmittable] and the potential interruption of that? So there definitely needs to be a sexual health context and conversation, especially if the woman is in a sero-discordant relationship. So at that point, it’s not just a woman conversation, it’s a whole relationship conversation. What’s her support system look like? If she has other family members that are heavily invested and involved in keeping her healthy, like say for example, in the Black community, we tend to be multi-generational as far as living arrangements, parents, grandparents, grandchildren. If my mother is living with me, is it going to freak her out to know that I'm not taking my medication? How do I have that conversation with her? So those are things that need to be considered. The overall lifestyle of a woman needs to be considered.
Transgender and Gender-Diverse Individuals
Role of hormones		07	Biomedical Researcher	Inclusion obviously is the biggest issue, and being able to really answer questions around treatment interruption and cure research in this population, particularly, if they’re taking hormone therapy, because it does seem like hormones are playing a role here in terms of the immunology and virology
Needs for trauma-informed research		18	Community Member	There’s a certain level of built-in trauma, a desire to be seen, known, and felt as fully human, that people of trans experience have been denied mostly all their lives. Most people of trans experience at some point in their lives, if not most of the lives, have been denied that full recognition of their humanity… And come at me with that kind of compassion and empathy and humility and understanding and respect and see me and hear me in my full humanity. And then we can talk about the rest.

Table 4. Summary of considerations for increasing the meaningful women’s involvement in HIV Cure-Related research.

Inclusion of Women in HIV (Including Cure) Clinical Research Inclusion of Women in HIV (Including Cure) Clinical Studies:. Researchers should ensure broad representation, clear definitions, and accurate capture of gender identities. Inclusion can also be driven by the local and global epidemiology, scientific questions, and proactive enrollment goals. Common Challenges to Including Women in HIV Cure Clinical Research: There are multiple common challenges to including women in HIV cure research, including protocol-level challenges, medical and practical-level challenges, psychosocial challenges and institutional challenges. Research teams should prioritize to proactively reduce as many of these common challenges as possible, and design and implement HIV cure trials through the lenses of intersectionality.

Meaningful Participation of Women in HIV (Including Cure) Research Successful Trial Examples: The following were highlighted in some trials as successful tools in enrolling women in trials: the insistence and requirement to include women, respectful and holistic engagement of women, focus on scientific issues that matter for women, and trial design specific to a population aimed at answering a scientific question. Steps to Facilitate More Equitable Participation of Women: Protocol-level strategies were including women in research planning stages, having more lenient eligibility criteria, preparing clear enrollment plans for women, setting very intentional enrollment goals and implementing enrollment freezes when necessary. Implementation strategies include having frequent recruitment updates to research teams, reducing trial burdens as much as possible, and valuing women’s unique lived experiences. Institution-level strategies include involving sites that have adequate infrastructure and populations, recruiting women where they receive HIV care, involving primary care doctors, and having representation of women at all levels. Community engagement and outreach-related strategies include involving peer navigators, outreach workers or case managers, involving community members and CBOs as partners, using simple language, and sharing research results back to the community. Disaggregating Scientific Data by Sex and Gender: Data disaggregation by sex should occur as early as possible in the research process.There should be more standardized requirements for scientific abstracts and publications, and peer reviewers should recognize their role in making sure diligent reporting occurs. Data disaggregation is important to close scientific gaps and disparities, to help answer scientific questions, and to make people feel included in research. Testing Interventions in Women: Biological sex is an important variable when testing HIV cure interventions, particularly for host-directed therapies. Willingness to Undergo Invasive Procedures (e.g. biopsies): Women may be willing to undergo biopsies, and several factors affect willingness to donate biopsies (e.g. information about why biopsies are needed, level of invasiness, frequency, level of pain or pain medications involved, sedation, recovery time, and compensation for biopsies and for research-related injuries). People Who Can Bear Children: People should be given autonomy to make decisions with informed consent, and there should be robust pre-clinical data to understand potential reproductive risks. Researchers should follow recommendations to make contraceptive requiremens more person- and women-centered^54—for example, thinking carefully about these requirements for people from the LGTBQAI + community.

Women and HIV Treatment Interruptions Women’s Willingness to Interrupt HIV Treatment: Facilitators to HIV treatment interruptions included frequent clinical monitoring, helping ensure representation of women, and long-term side effects of study interventions. Potential ATI concerns were viral rebound, CD4 count decrease, inflammation, immune activation, health regression, contradicting ART adherence messages, having to relearn ART adherence after an ATI, changes in ART regimens, and challenges for women trying to conceive. Considerations for Women Undergoing ATIs centered around avoiding risks related to pregnancy and/or breast/chest-feeding, establishing relationships of trust and mechanisms for communication, involving primary care doctors in conversations, and adopting a holistic approach to ATIs (e.g. mental health checks). Considerations related to partner protections included understanding partnership status, offering adequate counseling and disclosure support, and adopting principles of trauma-informed research.

Additional Considerations Logistical Aspects for Women: Logistical considerations included offering transportation, childcare, customized support, flexibility with study visits (including home visits), meaningful financial incentives, minimized paperwork, birth control, mental health support, and linkages with CBOs who can offer wrap-around services outside of clinical trials if needed. Transgender and Gender Diverse Individuals: Attention should be paid to the role of sex hormones and gender-affirming care, as well as social factors (e.g. discrimination, stigma, stress, violence, economic vulnerabilities).

Namiba A, Kwardem L, Dhairyawan R, et al. From presumptive exclusion towards fair inclusion: perspectives on the involvement of women living with HIV in clinical trials, including stakeholders’ views. Ther Adv Infect Dis. 2022;9:20499361221075454.

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