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

BACKGROUND: Cisgender women represent over half of people living with HIV globally. However, current research efforts toward a cure for HIV focus predominantly on cisgender men. The under-representation of women in HIV cure clinical studies is particularly problematic given data suggesting that sex-dependent phenotypes limit scientific discovery. OBJECTIVE: We aimed to generate considerations to increase the meaningful involvement of women in HIV cure-related research. MATERIALS AND METHODS: We conducted in-depth interviews with biomedical researchers and community members to better understand factors that could increase the meaningful involvement of women in HIV cure clinical trials. Participants were affiliated with academia, industry, community advisory boards, and community-based organizations, and were identified using listings from the AIDS Clinical Trials Group and the Martin Delaney Collaboratories. We used conventional content analysis to analyze the qualitative data. RESULTS: We recruited 27 participants, of whom 11 were biomedical researchers and 16 were community members. Participants included 25 cisgender women, 1 transgender woman, and 1 cisgender man. Key considerations emerged, including the need to ensure that HIV cure studies reflect HIV epidemiologic trends and having accurate representation by sex and gender in HIV cure research. To increase the meaningful involvement of women, recommendations included instituting intentional enrollment goals, frequent and mandatory reporting on enrollment, and incentives for sites to enroll women. Additional themes included the need for agency and self-determination, attention to lived experiences, trauma and healing, and adequate support for women (e.g. logistical, psychosocial, mental, emotional, and physical). Participants noted that women would be willing to participate in HIV cure trials, related procedures (e.g. biopsies), and analytical treatment interruptions. They also expressed a desired for women-centered and holistic clinical trial designs that account for intersectionality. CONCLUSIONS: Our empirical inquiry extends recent calls to action to increase diversity of people involved in HIV cure research. Redressing the under-inclusion of women in HIV cure research is an urgent imperative. The entire field must mobilize and reform to achieve this goal. Meaningfully involving women across the gender spectrum in HIV cure research is needed to ensure that interventions are safe, effective, scalable, and acceptable for all people with HIV.

Willingness of Racially Diverse Young Adults Living with HIV to Participate in HIV Cure Research: A Cross-Sectional Survey in the United States.

Nearly half of new HIV cases in the United States are among youth. Little is known about the willingness of young adults living with HIV (YLWH) to participate in HIV cure-related research. In 2021, we recruited 271 YLWH aged 18-29 for an online survey. We asked questions about willingness to participate in HIV cure research, perceived risks and benefits, acceptable trade-offs, and perceptions on analytical treatment interruptions. We conducted descriptive analyses to summarize data and bivariate analyses to explore correlations by demographics. Most respondents (mean age = 26) identified as men (86%) and Black Americans (69%). YLWH expressed high willingness to consider participating in cell- and gene-based approaches (75%) and immune-based approaches (71%). Approximately 45% would be willing to let their viral load become detectable for a period of time during an HIV cure study, 27% would not be willing, and 28% did not know. The social risk most likely to deter participation was the possibility of transmitting HIV to sex partners while off HIV medications (65% of respondents would be deterred a great deal or a lot). Compared to the 25-29 age group (n = 192), the 18-24 age group (n = 79) was more likely to indicate that having to disclose HIV status would matter a great deal in considering participation in HIV cure research (38% vs. 21%, p = .003). Inclusion and engagement of YLWH are critical for advancing novel HIV curative agents. Our article concludes with possible considerations for engaging YLWH in HIV cure research. Physical, clinical, and social risks will need to be kept to a minimum, and research teams will need to proactively mitigate the possibility of transmitting HIV to sex partners while off HIV medications.

Living with COVID-19 and preparing for future pandemics: revisiting lessons from the HIV pandemic.

In April, 2020, just months into the COVID-19 pandemic, an international group of public health researchers published three lessons learned from the HIV pandemic for the response to COVID-19, which were to: anticipate health inequalities, create an enabling environment to support behavioural change, and engage a multidisciplinary effort. We revisit these lessons in light of more than 2 years' experience with the COVID-19 pandemic. With specific examples, we detail how inequalities have played out within and between countries, highlight factors that support or impede the creation of enabling environments, and note ongoing issues with the scarcity of integrated science and health system approaches. We argue that to better apply lessons learned as the COVID-19 pandemic matures and other infectious disease outbreaks emerge, it will be imperative to create dialogue among polarised perspectives, identify shared priorities, and draw on multidisciplinary evidence.

"I Would Absolutely Need to Know That My Partner Is Still Going to be Protected": Perceptions of HIV Cure-Related Research Among Diverse HIV Serodifferent Couples in the United States.

Most HIV cure studies remain in the early stage of investigation and may carry clinical risks to the participants and, in some cases, their partners. Surprisingly little sociobehavioral research has investigated the perceptions of couples-including HIV serodifferent couples-around HIV cure research, including factors that would influence recruitment and retention in trials. We conducted a qualitative study to explore perceptions of diverse HIV serodifferent partners in the United States. We recruited 10 diverse HIV serodifferent couples (20 participants). We found participants had learned to cope with the reality of HIV, including protections during sex, and ascribed both positive and negative meanings to an HIV cure. Partners expressed concern about each other's health and potentially caring for a sick partner and emphasized the importance of safety when participating in an HIV cure trial. They identified the need for partner protection measures during analytical treatment interruptions (ATIs) as an ethical imperative. Participants recounted experiences of HIV stigma due to being in HIV serodifferent relationships and viewed ATIs as leading to a detectable viral load, which could limit sexual expression, complicate disclosure decision making, and worsen HIV-related stigma. Our study's main contribution is to inform efforts to meaningfully engage diverse HIV serodifferent partners in HIV cure research in the United States. Our data suggest people with HIV make decisions to participate in research based on close ones in their life and underscore the critical importance of acknowledging relationship dynamics in decisions to participate in research.

"It comes altogether as one:" perceptions of analytical treatment interruptions and partner protections among racial, ethnic, sex and gender diverse HIV serodifferent couples in the United States.

BACKGROUND: Most HIV cure-related studies involve interrupting antiretroviral treatment to assess the efficacy of pharmacologic interventions - also known as analytical treatment interruptions (ATIs). ATIs imply the risk of passing HIV to sexual partners due to the loss of undetectable HIV status. There has been a notable lack of attention paid to perceptions of ATIs among racial, ethnic, sex and gender minorities, and HIV serodifferent couples. These populations are among those most impacted by HIV in the United States. Future HIV cure research paradigms should equitably include considerations from these groups. METHODS: From August - October 2020, we conducted in-depth interviews with 10 racial, ethnic, sex, and gender minority HIV serodifferent couples in geographically diverse regions of the United States to understand their perspectives about ATIs and partner protection measures to prevent secondary HIV transmissions because of participation in ATI studies. We used framework analysis to analyze the qualitative data. RESULTS: Of the 10 couples recruited, four identified as a gay couple, two as a gay and bisexual couple, two as a heterosexual couple, one as a gay and queer couple, and one as a queer couple. We found that HIV serodifferent couples in our study viewed ATIs as contradicting HIV treatment adherence messages. Couples expressed discomfort around ATIs in HIV cure research. They were concerned with the return of HIV detectability and worried ATIs might result in secondary HIV transmission. Participants were strongly in favor of using a range of partner protection measures during ATIs that included PrEP, HIV risk reduction counseling, and alternatives for penetrative sex practices. Couples also recommended that sex partners be consulted or involved as part of ATI trials. CONCLUSIONS: Our findings highlight new potential opportunities and strategies to mitigate risk of HIV transmission during ATIs among key groups historically under-represented in HIV cure research. Findings also underscore the relational aspects of ATI trials. We provide preliminary considerations for planning ATI trials with diverse HIV serodifferent partners. Future studies should continue to explore these issues among other types of partnerships, cultures, and socio-cultural settings.

Implementation Strategies for Creating Inclusive, All-Women HIV Care Environments: Perspectives From Trans and Cis Women.

INTRODUCTION: Transgender (trans) women in the United States have disproportionately high rates of HIV acquisition, yet there remains a dearth of culturally appropriate and gender affirming HIV care services for them. Trans women often are aggregated with men who have sex with men based on biological essentialism and behaviorally defined characteristics, even though they have more in common with cisgender (cis) women, such as gender identity and psychosocial factors that influence HIV risk. As a result, trans women often are rendered invisible and underserved in the HIV response. We explore the feasibility of constructing inclusive, all-women HIV care environments as a way to redress the dearth of appropriate services for trans women living with HIV and to affirm their gender identity as women. METHODS: Thirty-eight women living with HIV and five providers participated in a qualitative focus group and interview study between April 2016 and January 2017, exploring the desirability and practicality of including trans women in HIV treatment and support services traditionally focused on cis women. Transcripts were coded and template analysis was employed to discern key themes. RESULTS: Participants identified concrete strategies for implementation of inclusive, all-women HIV care related to representation and visibility of trans women, community input, education and training, aspects of the clinic environment, and flexibility and creativity. The impact of trauma and the need for safety and gender affirmation were emphasized throughout. CONCLUSIONS: Trans and cis women found the idea of inclusive, all-women's HIV care environments attractive and feasible, notwithstanding cultural and structural challenges to creating them.

HIV and women in the USA: what we know and where to go from here.

New diagnoses of HIV infection have decreased among women in the USA overall, but marked racial and geographical disparities persist. The federal government has announced an initiative that aims to decrease the number of new infections in the nation by 90% within the next 10 years. With this in mind, we highlight important recent developments concerning HIV epidemiology, comorbidities, treatment, and prevention among women in the USA. We conclude that, to end the US HIV epidemic, substantially greater inclusion of US women in clinical research will be required, as will better prevention and treatment efforts, with universal access to health care and other supportive services that enable women to exercise agency in their own HIV prevention and care. Ending the epidemic will also require eliminating the race, class, and gender inequities, as well as the discrimination and structural violence, that have promoted and maintained the distribution of HIV in the USA, and that will, if unchecked, continue to fuel the epidemic in the future.

Altruism: Scoping review of the literature and future directions for HIV cure-related research.

INTRODUCTION: The question of what motivates people to participate in research is particularly salient in the HIV field. While participation in HIV research was driven by survival in the 1980's and early 1990's, access to novel therapies became the primary motivator with the advent of combination antiretroviral therapy (cART) in the late 1990s. In the HIV cure-related research context, the concept of altruism has remained insufficiently studied. METHODS: We conducted a scoping review to better contextualize and understand how altruism is or could be operationalized in HIV cure-related research. We drew from the fields of altruism in general, clinical research, cancer, and HIV clinical research-including the HIV prevention, treatment, and cure-related research fields. DISCUSSION: Altruism as a key motivating factor for participation in clinical research has often been intertwined with the desire for personal benefit. The cancer field informs us that reasons for participation usually are multi-faceted and complex. The HIV prevention field offers ways to organize altruism-either by the types of benefits achieved (e.g., societal versus personal), or the origin of the values that motivate research participation. The HIV treatment literature reveals the critical role of clinical interactions in fostering altruism. There remains a dearth of in-depth knowledge regarding reasons surrounding research participation and the types of altruism displayed in HIV cure-related clinical research. CONCLUSION: Lessons learned from various research fields can guide questions which will inform the assessment of altruism in future HIV cure-related research.

We Are All Women: Barriers and Facilitators to Inclusion of Transgender Women in HIV Treatment and Support Services Designed for Cisgender Women.

Transgender women share more in common with cisgender women, with respect to sociocultural context and factors influencing HIV risk and outcomes, than they do with "men who have sex with men", a behavioral risk category in which they often are included. However, it is not yet clear whether both transgender and cisgender women would find integrated, all-women HIV programs and services desirable and beneficial. We Are All Women was a qualitative study conducted in the San Francisco Bay Area from April 2016 to January 2017, using a conceptual framework based on gender affirmation and trauma-informed care, to explore barriers and facilitators to inclusion of transgender women in HIV treatment and support services traditionally focused on cisgender women. Thirty-eight women (10 trans, 25 cis, and 3 "other" gender) participated in six semistructured, facilitated focus groups. In addition, five HIV care providers participated in semistructured, in-depth interviews. Both trans and cis women identified the desire for gender affirmation, a feeling of safety (specifically space without men), and potential community building within a care and healing context as powerful facilitators of an inclusive all-women care environment. At the same time, they recognized that tensions do exist between idealized visions of such an environment, deep-seated sentiments and behaviors among some cis women toward trans women, and the practical realities of creating the optimal spaces for all women. Opportunities for dialog between trans and cis women to mitigate gender-associated phobias and misperceptions are a valuable first step in creating HIV care environments that serve all women.

A tale of two cascades: promoting a standardized tool for monitoring progress in HIV prevention.

INTRODUCTION: To achieve significant progress in global HIV prevention from 2020 onward, it is essential to ensure that appropriate programmes are being delivered with high quality and sufficient intensity and scale and then taken up by the people who most need and want them in order to have both individual and public health impact. Yet, currently, there is no standard way of assessing this. Available HIV prevention indicators do not provide a logical set of measures that combine to show reduction in HIV incidence and allow for comparison of success (or failure) of HIV prevention programmes and for monitoring progress in meeting global targets. To redress this, attention increasingly has turned to the prospects of devising an HIV prevention cascade, similar to the now-standard HIV treatment cascade; but this has proven to be a controversial enterprise, chiefly due to the complexity of primary prevention. DISCUSSION: We address a number of core issues attendant with devising prevention cascades, including: determining the population of interest and accounting for the variability and fluidity of HIV-related risk within it; the fact that there are multiple HIV prevention methods, and many people are exposed to a package of them, rather than a single method; and choosing the final step (outcome) in the cascade. We propose two unifying models of prevention cascades-one more appropriate for programme managers and monitors and the other for researchers and programme developers-and note their relationship. We also provide some considerations related to cascade data quality and improvement. CONCLUSIONS: The HIV prevention field has been grappling for years with the idea of developing a standardised way to regularly assess progress and to monitor and improve programmes accordingly. The cascade provides the potential to do this, but it is complicated and highly nuanced. We believe the two models proposed here reflect emerging consensus among the range of stakeholders who have been engaging in this discussion and who are dedicated to achieving global HIV prevention goals by ensuring the most appropriate and effective programmes and methods are supported.

Cognitive testing of an instrument to evaluate acceptability and use of pre-exposure prophylaxis products among women.

Given the range of pre-exposure prophylaxis (PrEP) products currently being tested to prevent HIV in women, a standardized Acceptability and Use of PrEP Products Among Women Tool may facilitate comparisons of product acceptability and use across different geographies, trials, and users. We conducted three rounds of cognitive interviewing over 2 months in 2016, with 28 South African women who had experience participating in a range of PrEP product trials. The final instrument contained 41 items, including five new items that improved construct validity and 22 items modified for clarity. Changes were made due to unclear wording, difficulty answering, participant embarrassment, low response variability, and administrative formatting. Cognitive interviewing provided a means to address issues that would have inhibited this tool's ability to accurately collect data otherwise. This rapid, low-cost study provided valuable insight into participants' understanding of questions and demonstrated the utility of cognitive interviewing in international clinical trials.

The Dose Response: Perceptions of People Living with HIV in the United States on Alternatives to Oral Daily Antiretroviral Therapy.

There are two concurrent and novel major research pathways toward strategies for HIV control: (1) long-acting antiretroviral therapy (ART) formulations and (2) research aimed at conferring sustained ART-free HIV remission, considered a step toward an HIV cure. The importance of perspectives from people living with HIV on the development of new modalities is high, but data are lacking. We administered an online survey in which respondents selected their likelihood of participation or nonparticipation in HIV cure/remission research based on potential risks and perceived benefits of these new modalities. We also tested the correlation between perceptions of potential risks and benefits with preferences of virologic control strategies and/or responses to scenario choices, while controlling for respondent characteristics. Of the 282 eligible respondents, 42% would be willing to switch from oral daily ART to long-acting ART injectables or implantables taken at 6-month intervals, and 24% to a hypothetical ART-free remission strategy. We found statistically significant gender differences in perceptions of risk and preferences of HIV control strategies, and possible psychosocial factors that could mediate willingness to switch to novel HIV treatment or remission options. Our study yielded data on possible desirable product characteristics for future HIV treatment and remission options. Findings also revealed differences in motivations and preferences across gender and other sociodemographic characteristics that may be actionable as part of research recruitment efforts. The diversity of participant perspectives reveals the need to provide a variety of therapeutic options to people living with HIV and to acknowledge their diverse experiential expertise when developing novel HIV therapies.

Getting to Zero Begins With Getting to Ten.

BACKGROUND STATEMENT: The global "90-90-90" targets introduced by UNAIDS in 2014-90% of people living with HIV will know their HIV status; 90% of those will be on antiretroviral treatment; and 90% of those will achieve viral suppression by 2020-have become more than a useful heuristic device, and now are the predominant framework for monitoring progress in the HIV response. Although this allows for important reflection on where HIV treatment gaps and opportunities exist in any particular context and globally, it deflects attention away from other very important aspects of HIV epidemics and their often-disproportionate impact on specific populations. Most significantly, it begs the question, what about the other 10-10-10? APPROACH: This article takes a critical look at the 90-90-90 targets and what is known about the 10-10-10 left behind to highlight some core issues and attendant questions that should be prioritized if we really intend to "get to zero." FINDINGS AND CONCLUSIONS: These issues include how the targets are measured in the first place, the limitations of focusing the global response only on antiretroviral treatment and only on people already living with HIV, and the need for more, basic social research to address the range of factors underlying disparities in who are and are not reached in the 90-90-90 framework.

Applying the Behavioural and Social Sciences Research (BSSR) Functional Framework to HIV Cure Research.

INTRODUCTION: The search for an HIV cure involves important behavioural and social processes that complement the domains of biomedicine. However, the field has yet to tap into the full potential of behavioural and social sciences research (BSSR). In this article, we apply Gaist and Stirratt's BSSR Functional Framework to the field of HIV cure research. DISCUSSION: The BSSR Functional Framework describes four key research domains: (1) basic BSSR (understanding basic behavioural and social factors), (2) elemental BSSR (advancing behavioural and social interventions), (3) supportive BSSR (strengthening biomedically focused clinical trials), and (4) integrative BSSR (building multi-disciplinary combination approaches for real-world implementation). In revisiting and applying the BSSR Functional Framework, we clarify the importance of BSSR in HIV cure research by drawing attention to such things as: how language and communication affect the meaning of "cure" to people living with HIV (PLHIV) and broader communities; how cure affects the identity and social position of PLHIV; counselling and support interventions to address the psychosocial needs and concerns of study participants related to analytical treatment interruptions (ATIs); risk reduction in the course of ATI study participation; motivation, acceptability, and decision-making processes of potential study participants related to different cure strategies; HIV care providers' perceptions and attitudes about their patients' participation in cure research; potential social harms or adverse social events associated with cure research participation; and the scalability of a proven cure strategy in the context of further advances in HIV prevention and treatment. We also discuss the BSSR Functional Framework in the context of ATIs, which involve processes at the confluence of the BSSR domains. CONCLUSIONS: To move HIV cure regimens through the translational research pathway, attention will need to be paid to both biomedical and socio-behavioural elements. BSSR can contribute an improved understanding of the human and social dimensions related to HIV cure research and the eventual application of HIV cure regimens. The BSSR Functional Framework provides a way to identify advances, gaps and opportunities to craft an integrated, multi-disciplinary approach at all stages of cure research to ensure the real-world applicability of any strategy that shows promise.

If We Build It, Will They Come? Perceptions of HIV Cure-Related Research by People Living with HIV in Four U.S. Cities: A Qualitative Focus Group Study.

Global interest and investment in the search for an HIV cure has increased. Research has focused on what experts refer to as a sterilizing or eradicating cure, where HIV is eliminated from the body, and on what is often called a functional cure, where HIV remains, kept durably suppressed in the absence of antiretroviral treatment and therapy (ART). Many believe that a functional cure is likely to be found first. HIV cure studies will require active participation by people living with HIV (PLWHIV). Their desires and perceptions will be important to effectively recruit study participants and for the uptake of any future strategy that demonstrates safety and efficacy. The perspectives of PLWHIV are essential to advancing HIV cure research, and they should be taken into consideration as biomedical research advances. We conducted 10 focus groups in four U.S. cities, eliciting perspectives of PLWHIV on HIV cure and cure research. Most participants conceived of a cure as eradicating, and felt favorably toward it. In addition to the physical benefits of a potential cure, participants valued the possible de-stigmatization related to no longer living with HIV, liberation from concerns about transmitting HIV, and freedom from the burden of daily medication. Many participants did not regard a functional cure as an improvement over controlling HIV through ART, were distrustful about viral rebound potential, and noted concerns about medical complications and accompanying psychological distress. Some felt that the risks of HIV cure research were not worth taking. Many were skeptical about science's ability to eliminate HIV from the body.

Towards an integrated primary and secondary HIV prevention continuum for the United States: a cyclical process model.

INTRODUCTION: Every new HIV infection is preventable and every HIV-related death is avoidable. As many jurisdictions around the world endeavour to end HIV as an epidemic, missed HIV prevention and treatment opportunities must be regarded as public health emergencies, and efforts to quickly fill gaps in service provision for all people living with and vulnerable to HIV infection must be prioritized. DISCUSSION: We present a novel, comprehensive, primary and secondary HIV prevention continuum model for the United States as a conceptual framework to identify key steps in reducing HIV incidence and improving health outcomes among those vulnerable to, as well as those living with, HIV infection. We further discuss potential approaches to address gaps in data required for programme planning, implementation and evaluation across the elements of the HIV prevention continuum. CONCLUSIONS: Our model conceptualizes opportunities to monitor and quantify primary HIV prevention efforts and, importantly, illustrates the interplay between an outcomes-oriented primary HIV prevention process and the HIV care continuum to move aggressively forward in reaching ambitious reductions in HIV incidence. To optimize the utility of this outcomes-oriented HIV prevention continuum, a key gap to be addressed includes the creation and increased coordination of data relevant to HIV prevention across sectors.

Towards Multidisciplinary HIV-Cure Research: Integrating Social Science with Biomedical Research.

The quest for a cure for HIV remains a timely and key challenge for the HIV research community. Despite significant scientific advances, current HIV therapy regimens do not completely eliminate the negative impact of HIV on the immune system; and the economic impact of treating all people infected with HIV globally, for the duration of their lifetimes, presents significant challenges. This article discusses, from a multidisciplinary approach, critical social, behavioral, ethical, and economic issues permeating the HIV-cure research agenda. As part of a search for an HIV cure, both the perspective of patients/participants and clinical researchers should be taken into account. In addition, continued efforts should be made to involve and educate the broader community.