Including transgender populations in mathematical models for HIV treatment and prevention: current barriers and policy implications.

INTRODUCTION: Mathematical models of HIV have been uniquely important in directing and evaluating HIV policy. Transgender and nonbinary people are disproportionately impacted by HIV; however, few mathematical models of HIV transmission have been published that are inclusive of transgender and nonbinary populations. This commentary discusses current structural challenges to developing robust and accurate trans-inclusive models and identifies opportunities for future research and policy, with a focus on examples from the United States. DISCUSSION: As of April 2024, only seven published mathematical models of HIV transmission include transgender people. Existing models have several notable limitations and biases that limit their utility for informing public health intervention. Notably, no models include transgender men or nonbinary individuals, despite these populations being disproportionately impacted by HIV relative to cisgender populations. In addition, existing mathematical models of HIV transmission do not accurately represent the sexual network of transgender people. Data availability and quality remain a significant barrier to the development of accurate trans-inclusive mathematical models of HIV. Using a community-engaged approach, we developed a modelling framework that addresses the limitations of existing model and to highlight how data availability and quality limit the utility of mathematical models for transgender populations. CONCLUSIONS: Modelling is an important tool for HIV prevention planning and a key step towards informing public health interventions, programming and policies for transgender populations. Our modelling framework underscores the importance of accurate trans-inclusive data collection methodologies, since the relevance of these analyses for informing public health decision-making is strongly dependent on the validity of the model parameterization and calibration targets. Adopting gender-inclusive and gender-specific approaches starting from the development and data collection stages of research can provide insights into how interventions, programming and policies can distinguish unique health needs across all gender groups. Moreover, in light of the data structure limitations, designing longitudinal surveillance data systems and probability samples will be critical to fill key research gaps, highlight progress and provide additional rigour to the current evidence. Investments and initiatives like Ending the HIV Epidemic in the United States can be further expanded and are highly needed to prioritize and value transgender populations across funding structures, goals and outcome measures.

Recommendations on data sharing in HIV drug resistance research.

• Human immunodeficiency virus (HIV) drug resistance has implications for antiretroviral treatment strategies and for containing the HIV pandemic because the development of HIV drug resistance leads to the requirement for antiretroviral drugs that may be less effective, less well-tolerated, and more expensive than those used in first-line regimens. • HIV drug resistance studies are designed to determine which HIV mutations are selected by antiretroviral drugs and, in turn, how these mutations affect antiretroviral drug susceptibility and response to future antiretroviral treatment regimens. • Such studies collectively form a vital knowledge base essential for monitoring global HIV drug resistance trends, interpreting HIV genotypic tests, and updating HIV treatment guidelines. • Although HIV drug resistance data are collected in many studies, such data are often not publicly shared, prompting the need to recommend best practices to encourage and standardize HIV drug resistance data sharing. • In contrast to other viruses, sharing HIV sequences from phylogenetic studies of transmission dynamics requires additional precautions as HIV transmission is criminalized in many countries and regions. • Our recommendations are designed to ensure that the data that contribute to HIV drug resistance knowledge will be available without undue hardship to those publishing HIV drug resistance studies and without risk to people living with HIV.

A Quantitative Intersectionality Analysis of HIV/STI Prevention and Healthcare Access Among Transgender and Nonbinary People.

BACKGROUND: Transgender and nonbinary people experience substantial barriers to accessing healthcare, including prevention of HIV and other sexually transmitted infections (HIV/STI), due to structural inequities. We examined differences in insurance, HIV/STI prevalence, testing, and preexposure prophylaxis use among transgender and nonbinary people living in Washington State by race and ethnicity and gender. METHODS: We pooled data from five 2019-2021 Washington State HIV/STI surveillance data sources to obtain a large and diverse sample of 1648 transgender and nonbinary participants. We calculated the risk difference (RD) for each outcome and used Poisson regression to estimate a surrogate measure of additive interaction-attributable proportion (AP)-that measures the proportion of the excess prevalence of the outcome observed at the intersection of gendered and racialized experience, beyond that expected from gender or race and ethnicity alone. RESULTS: Participants reported overall high levels of poverty (29% incomes <$15,000 and 7% unstable housing). Certain groups, especially racial/ethnic minority transgender women, were disproportionately impacted by HIV/STIs (RDs from 20% to 43% and APs from 50% to 85%) and less likely to currently have insurance (RDs from 25% to 39% and APs from 74% to 93%) than that expected based on gendered or racialized experience alone. CONCLUSIONS: Our findings highlight the heterogeneity in insurance access, HIV/STI positivity, and prevention utilization within transgender communities. We observed that a large proportion of increased HIV/STI prevalence among racial/ethnic minority transgender women was attributable to the intersection of gender and race and ethnicity. Our findings highlight the importance of trans-inclusive models of HIV/STI prevention that address multilevel barriers rooted in cissexism and structural racism.

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.

Lessons learned from community engagement regarding phylodynamic research with molecular HIV surveillance data.

INTRODUCTION: The widespread implementation of molecular HIV surveillance (MHS) has resulted in an increased discussion about the ethical, human rights and public health implications of MHS. We narrate our process of pausing our research that uses data collected through MHS in response to these growing concerns and summarize the key lessons we learned through conversations with community members. METHODS: The original study aimed to describe HIV transmission patterns by age and race/ethnicity among men who have sex with men in King County, Washington, by applying probabilistic phylodynamic modelling methods to HIV-1 pol gene sequences collected through MHS. In September 2020, we paused the publication of this research to conduct community engagement: we held two public-facing online presentations, met with a national community coalition that included representatives of networks of people living with HIV, and invited two members of this coalition to provide feedback on our manuscript. During each of these meetings, we shared a brief presentation of our methods and findings and explicitly solicited feedback on the perceived public health benefit and potential harm of our analyses and results. RESULTS: Some community concerns about MHS in public health practice also apply to research using MHS data, namely those related to informed consent, inference of transmission directionality and criminalization. Other critiques were specific to our research study and included feedback about the use of phylogenetic analyses to study assortativity by race/ethnicity and the importance of considering the broader context of stigma and structural racism. We ultimately decided the potential harms of publishing our study-perpetuating racialized stigma about men who have sex with men and eroding the trust between phylogenetics researchers and communities of people living with HIV-outweighed the potential benefits. CONCLUSIONS: HIV phylogenetics research using data collected through MHS data is a powerful scientific technology with the potential to benefit and harm communities of people living with HIV. Addressing criminalization and including people living with HIV in decision-making processes have the potential to meaningfully address community concerns and strengthen the ethical justification for using MHS data in both research and public health practice. We close with specific opportunities for action and advocacy by researchers.

Mapping Community-Engaged Implementation Strategies with Transgender Scientists, Stakeholders, and Trans-Led Community Organizations.

PURPOSE OF REVIEW: Pre-exposure prophylaxis (PrEP) represents one of the most effective methods of prevention for HIV, but remains inequitable, leaving many transgender and nonbinary (trans) individuals unable to benefit from this resource. Deploying community-engaged PrEP implementation strategies for trans populations will be crucial for ending the HIV epidemic. RECENT FINDINGS: While most PrEP studies have progressed in addressing pertinent research questions about gender-affirming care and PrEP at the biomedical and clinical levels, research on how to best implement gender-affirming PrEP systems at the social, community, and structural levels remains outstanding. The science of community-engaged implementation to build gender-affirming PrEP systems must be more fully developed. Most published PrEP studies with trans people report on outcomes rather than processes, leaving out important lessons learned about how to design, integrate, and implement PrEP in tandem with gender-affirming care. The expertise of trans scientists, stakeholders, and trans-led community organizations is essential to building gender-affirming PrEP systems.

Heterogeneity in HIV/Sexually Transmitted Infection Prevalence and Prevention Among the Partners of Transgender and Nonbinary People.

BACKGROUND: Transgender and nonbinary (TNB) people are diverse in their sexual orientation and partnerships. We describe the epidemiology of HIV/sexually transmitted infection (STI) prevalence and prevention utilization among the partners of TNB people in Washington State. METHODS: We pooled data from five 2017 to 2021 cross-sectional HIV surveillance data sources to generate a large sample of TNB people and cisgender people who had a TNB partner in the past year. We described characteristics of recent partners of trans women, trans men, and nonbinary people and used Poisson regression to assess if having a TNB partner was associated with self-reported HIV/STIs prevalence, testing, and preexposure prophylaxis (PrEP) use. RESULTS: Our analysis included 360 trans women, 316 trans men, 963 nonbinary people, 2896 cis women, and 7540 cis men. Overall, 9% of sexual minority cis men, 13% of sexual minority cis women, and 36% of TNB participants reported having any TNB partners. There was significant heterogeneity in HIV/STI prevalence, testing, and PrEP use among the partners of TNB people by study participant gender and the gender of their sex partners. In regression models, having a TNB partner was associated with a higher likelihood of HIV/STI testing and PrEP use but was not associated with higher HIV prevalence. CONCLUSIONS: We observed significant heterogeneity in HIV/STI prevalence and preventative behaviors among the partners of TNB people. Given that TNB people are diverse in their sexual partnerships, there is a need to better understand individual-, dyad-, and structural-level factors that facilitate HIV/STI prevention across these diverse partnerships.

Addressing Ethical Challenges in US-Based HIV Phylogenetic Research.

In recent years, phylogenetic analysis of HIV sequence data has been used in research studies to investigate transmission patterns between individuals and groups, including analysis of data from HIV prevention clinical trials, in molecular epidemiology, and in public health surveillance programs. Phylogenetic analysis can provide valuable information to inform HIV prevention efforts, but it also has risks, including stigma and marginalization of groups, or potential identification of HIV transmission between individuals. In response to these concerns, an interdisciplinary working group was assembled to address ethical challenges in US-based HIV phylogenetic research. The working group developed recommendations regarding (1) study design; (2) data security, access, and sharing; (3) legal issues; (4) community engagement; and (5) communication and dissemination. The working group also identified areas for future research and scholarship to promote ethical conduct of HIV phylogenetic research.