Perceptions about doxycycline post-exposure prophylaxis (Doxy-PEP) as an STI-prevention strategy among gay and bisexual men (GBM) in the United States: Results from a qualitative study.

OBJECTIVE: To leverage qualitative data to explore gay and bisexual men's (GBM) perceptions about doxycycline post-exposure prophylaxis (Doxy-PEP). Doxy-PEP is a novel biomedical STI-prevention strategy that helps reduce the risk of acquiring bacterial STIs. Little is known about Doxy-PEP's acceptability in the U.S., nor how best to engage those most vulnerable to STIs in taking up this nascent prevention strategy. METHOD: Between July and September of 2023, 24 GBM from across the U.S. completed qualitative interviews about their perceptions regarding Doxy-PEP. Interviews were analyzed using a codebook approach to thematic analysis. RESULTS: Participants were generally interested in using Doxy-PEP, but were concerned about the potential for antibiotic resistance, side-effects, medication interactions to occur, along with stigmatizing discourse around its use. Meanwhile, participants were motivated by the simplicity of Doxy-PEP and the protection it could confer on both an individual and community-level- as well as its potential to reduce STI-related anxiety. Finally, participants desired additional information on Doxy-PEP to address their concerns. CONCLUSIONS: There is a need for clear guidelines and expanded public health messaging on Doxy-PEP in the U.S.

PrEP Uptake and Methamphetamine Use Patterns in a 4-Year U.S. National Prospective Cohort Study of Sexual and Gender Minority People, 2017-2022.

Methamphetamine use is on the rise among sexual and gender minority people who have sex with men (SGMSM), escalating their HIV risk. Despite pre-exposure prophylaxis (PrEP) being an effective biomedical HIV prevention tool, its uptake in relation to methamphetamine use patterns in SGMSM has not been studied. In a U.S. cohort study from 2017 to 2022, 6,253 HIV-negative SGMSM indicated for but not using PrEP were followed for four years. Methamphetamine use was categorized (i.e., newly initiated, persistently used, never used, used but quit), and PrEP uptake assessed using generalized estimating equation (GEE), adjusted for attrition. Participants had a median age of 29, with 51.9% White, 11.1% Black, 24.5% Latinx, and 12.5% other races/ethnicities. Over the four years, PrEP use increased from 16.3 to 27.2%. GEE models identified risk factors including housing instability and food insecurity. In contrast, older age, health insurance, clinical indications, and prior PrEP use increased uptake. Notably, Latinx participants were more likely to use PrEP than Whites. Regarding methamphetamine use, those who newly initiated it were more likely to use PrEP compared to non-users. However, those who quit methamphetamine and those who persistently used it had PrEP usage rates comparable to those of non-users. Though PrEP uptake increased, it remained low in SGMSM. Methamphetamine use was associated with PrEP uptake. Healthcare providers should assess methamphetamine use for harm reduction. Prioritizing younger, uninsured SGMSM and addressing basic needs can enhance PrEP uptake and reduce HIV vulnerabilities.

Sexual and Gender Minorities' Vaccine Uptake and Behavioral Change in Response to the Mpox Outbreak in the United States: August 2022 Through November 2022.

BACKGROUND: In the summer of 2022, the United States faced a nationwide outbreak of mpox, with cases concentrated in sexual and gender minorities who have sex with men. Understanding rates of mpox vaccine uptake and concomitant behavioral change is essential to guide the implementation of targeted public health responses to the potential reemergence of mpox. METHODS: Between August 2022 and November 2022, 8551 individuals recruited via geosocial networking apps completed a brief survey that assessed mpox vaccine uptake, intentions to get a mpox vaccine, and behavioral change. RESULTS: In August, 17.4% of participants reported having received at least 1 dose of the mpox vaccine. By November, this prevalence estimate was 35.0%. Black participants were significantly less likely to be vaccinated, and vaccine hesitancy increased among Black participants over time. Among those who had not yet received a vaccination, the intention to get vaccinated decreased over time. We observed trends that coincided with the evolving outbreak, such as decreased worry about mpox and less engagement in risk reduction behaviors over time. CONCLUSIONS: Despite a 2-fold increase in mpox vaccine uptake between August 2022 and November 2022 in sexual and gender minorities who have sex with men, disparities in vaccine uptake were observed among Black participants. Findings will guide the implementation of public health responses to the potential reemergence of mpox and other viral infectious diseases (eg, meningitis) with a specific focus on optimizing vaccine uptake in Black communities.

'You have to trust their word': transmasculine experiences with sex partners and safety during the early COVID-19 outbreak.

The early months of the SARS-CoV2 pandemic exacerbated health disparities for vulnerable populations, including transgender (trans) communities, creating unique challenges for navigating sex and dating. This paper aims to expand upon the current literature regarding transmasculine populations by capturing their lived experiences during this critical time. We interviewed 20 assigned female sex at birth (AFAB) adults of the transmasculine spectrum - men, nonbinary, and transmasculine individuals - about their social and sexual experiences in the USA in May and June 2020. Transcripts were analysed using an inductive thematic approach. We found that sex drive decreased and uncertainty about health risks increased. Some participants found alternate ways to date and hook-up that reduced their COVID-19 risk, such as engaging in online sex (e.g. sexting, dating apps). Others expressed discomfort using virtual platforms for both personal/work and sexual lives, along with nuanced feelings around being objectified, compared to pornography, and fetishised as trans bodies. COVID-related shutdowns of queer spaces also amplified pre-existing concerns about interpersonal safety and rejection. When seeking new partners, participants sought behavioural characteristics that instilled trust. Future public health communications can take advantage of safety and sexual health strategies already present in trans communities to bolster wellbeing in trans lives.

Changes in Health Insurance During COVID-19 Among a U.S. National Cohort of Cisgender Gay and Bisexual Men and Transgender Individuals.

The extant data suggest that LGBT communities were disproportionately impacted by the economic ramifications of the pandemic and were more likely to report being uninsured throughout the first two years of the pandemic. Additionally, these groups are at heightened vulnerability for several health conditions that require insurance to manage or prevent. Thus, there is a need to assess changes in pandemic-era insurance coverage among these populations. This study uses data collected as part of the Together 5,000 study, a U.S. national, internet-based cohort study of cisgender men, trans men, and trans women who have sex with men. We analyze insurance data across three different assessments between 2019 and 2021, exploring changes in insurance coverage and type. Among our sample, 6.4% lost their insurance in 2020 because of the pandemic. Insurance loss was associated with living in a state that had not expanded Medicaid, race/ethnicity, employment status, and income. Among those who lost their insurance in early 2020, most (59.2%) reported gaining insurance by 2021, with those living in non-expanded states less likely to gain insurance. Finally, those who were uninsured prior to the pandemic were less likely to report gaining insurance by 2021, when compared to those uninsured as a result of the pandemic. This suggests that there are uninsured cisgender gay and bisexual men and transgender individuals that continue to go unreached by policies to assuage uninsurance. Further policy intervention is needed to address uninsurance among LGBT individuals, which has important implications for addressing health disparities among these populations.

Experiences of police-related stress among a U.S. national cohort of gay and bisexual men.

Marginalized groups (including people of Color and sexual minorities) have been over-policed and specifically targeted based on their race/ethnicity and identity. The deleterious effects of over-policing marginalized groups include overrepresentation in the carceral system, experiencing higher rates of violence from police, and extend to affect mental health and stress levels. This study examines police-related stress among a U.S. national cohort of gay and bisexual men (collected in late 2020 and early 2021) and its association with race/ethnicity, age, human immunodeficiency virus (HIV) status, income, and other characteristics of interest. Our results show that the odds of reporting extreme police-related stress were 2.7 (95% confidence interval [CI] [2.08, 3.41]) times higher for Black individuals than for their White counterparts. Odds were also significantly greater for those who have experienced race-based (odds ratio [OR] = 2.26, 95% CI [1.81-2.82] or identity-based discrimination (OR = 2.05, 95% CI [1.66, 2.54]). Our findings demonstrate variation in police-related stress among a cohort of gay and bisexual men; with men of Color and low-income men among the most affected by police-related stress. For this population, police-related stress should be considered for its potential deleterious effect on HIV vulnerability and reporting violent crimes to police (including intimate partner violence and hate crimes).

Changes in Cost and Insurance Challenges to Cover PrEP Between 2019 and 2021.

INTRODUCTION: Pre-Exposure Prophylaxis (PrEP) use continues lag estimated need among gay and bisexual men in the United States. Studies report that challenges paying for PrEP may undermine continued use. Our study aimed to measure these challenges over time. METHODS: Data were taken from a US national cohort study of cisgender gay and bisexual men and transgender individuals aged 16-49 years. We analyzed data from PrEP-using participants between 2019 and 2021 and observed cost-related and insurance-related challenges participants experienced while on PrEP across time points. We report McNemar and Cochrane Q test statistics to compare differences between groups by year(s). RESULTS: In 2019, 16.5% (n = 828/5013) of participants were on PrEP; by 2020, 21% (n = 995/4727) were on PrEP, and by 2021, 24.5% (n = 1133/4617) were on PrEP. The proportion of those experiencing challenges paying for PrEP care decreased significantly across time points for clinical appointments, laboratory work, and prescriptions. Those experiencing insurance and copay approval issues did not change significantly. Although not statistically significant, the only proportion that increased over time was those reporting PrEP-related insurance approval issues. In a post hoc analysis, we found that those reporting PrEP use in the past year who were not currently on PrEP were significantly more likely to report experiencing most PrEP challenges, when compared with current PrEP users. DISCUSSION: We found significant reductions in insurance and cost-related challenges between 2019 and 2021. However, those who discontinued PrEP within the past year reported greater challenges paying for PrEP, suggesting that cost and insurance issues may undermine PrEP persistence.

The Impact of the COVID-19 Pandemic on HIV-Positive Men Who Have Sex With Men: (Dis)connection to Social, Sexual, and Health Networks.

The COVID-19 pandemic has disproportionately affected HIV-positive cisgender men who have sex with men (MSM). Between May and June in 2020, we conducted one-on-one semi-structured qualitative interviews with 20 HIV-positive MSM aiming to describe their (dis)connection to social, sexual, and health networks during the COVID-19 pandemic. All participants relied on social support networks to manage pandemic-based distress, using computer-mediated communication as well as physical proximity. To connect to sexual networks, this sample described adaptations to their partner selection strategies, such as enumerating harm reduction approaches. To connect to health networks, participants depended on reassuring providers, resourceful case managers, telehealth, and streamlined access to their antiretroviral therapy (ART) medications. Nonetheless, stay-at-home recommendations reduced community connection, sexual activity, and healthcare access for many participants, and perceptions of these losses were shaped by psychosocial burdens (e.g., loneliness), structural burdens (e.g., environmental barriers, financial difficulties), and health-protective factors (e.g., hopeful outlook, adherence to a regular routine). The COVID-19 pandemic appears to have exacerbated health-related issues for HIV-positive MSM. Given the ongoing COVID-19 mutations, community-based organizations, clinicians, and researchers might use these findings to modify HIV prevention and intervention efforts.

Health and Access to Gender-Affirming Care During COVID-19: Experiences of transmasculine individuals and men assigned female sex at birth.

Since the onset of the COVID-19 pandemic, global research has suggested that the pandemic has negatively affected lesbian, gay, bisexual, transgender, and queer or questioning (LGBTQ) populations, including by limiting health care access. There is little research on the impact of COVID-19 among transmasculine persons and men assigned female sex at birth (AFAB) in the United States, who face unique health care challenges outside of the pandemic context. Between May and June of 2020, 20 transmasculine individuals and AFAB men who have sex with men participated in semi-structured interviews about their experiences during the early months of the COVID-19 pandemic. Participants were asked how the pandemic affected their access to health care, overall health, and well-being. Interviews were analyzed using an inductive, thematic approach. Participants reported reduced access to in-person health care, which in some cases meant overdue hormone-related bloodwork and unmet health care needs. Most participants reported that they were able to maintain their testosterone regimen, although some were concerned about future access, citing anxiety about potential shortages. Three participants reported canceled or deferred gender-affirming procedures, which they were uncertain would be rescheduled soon. Participants generally reported that the expansion of telehealth improved access to care, particularly for gender-affirming psychotherapy that was otherwise inaccessible or inconvenient prior to the pandemic. Other salient themes include the pandemic's impact on health behaviors and daily routines. Although the COVID-19 pandemic created new challenges for maintaining health, it also expanded access to gender-affirming health care, largely through the expansion of telehealth. Our findings provide new insights for supporting the health of transmasculine individuals and AFAB men.

Why Are Patients Switching from Tenofovir Disoproxil Fumarate/Emtricitabine (Truvada) to Tenofovir Alafenamide/Emtricitabine (Descovy) for Pre-Exposure Prophylaxis?

Safety differences between tenofovir alafenamide/emtricitabine (TAF) and tenofovir disoproxil fumarate/emtricitabine (TDF/FTC)-formulated pre-exposure prophylaxis (PrEP) appear to have little clinical significance for most PrEP users. Furthermore, generic TDF-formulated PrEP is projected to decrease the price of PrEP. Thus, efforts to shift PrEP users to TAF-formulated PrEP should be considered in light of their potential to undermine efforts to scale-up PrEP nationally. Data are taken from Together 5,000, a US national cohort study predominantly composed of cisgender gay and bisexual men. In 2019-2020, 5034 participants completed their 24-month assessment, which measured whether participants were switching from TDF (Truvada) to TAF (Descovy) for PrEP, and why. Of those reporting PrEP-use (n = 1009), 277 reported using Descovy for PrEP, and 223 provided a reason for switching to Descovy. A content analysis was used to code participant's reasons for switching. Over half (56%) of participants reported that their doctor recommended switching to Descovy. Without mentioning a provider recommendation, 32% of participants reported that perceived improved safety of Descovy, compared with Truvada, motivated their decision to change their prescription. Other factors cited included the smaller size of the pill and "newness" of Descovy. Further, several participants mentioned negative advertising about Truvada as rationale for switching. Although scientific consensus supports the safety of both TDF/FTC and TAF, our results suggest that current messaging through physicians and other sources have emphasized superior safety of TAF-implying that TDF/FTC may not be safe in the long term. Efforts to shift users onto TAF may undermine public perception of TDF-formulated PrEP.

How Has HIV Pre-Exposure Prophylaxis (PrEP) Changed Sex? A Review of Research in a New Era of Bio-behavioral HIV Prevention.

In 2012, the U.S. FDA approved the first drug for use as HIV Pre-Exposure Prophylaxis (PrEP), which is nearly 99% effective when taken as prescribed. Although the manifest function of PrEP is to prevent HIV infection in the event of exposure, the drug has also had a significant impact on various facets of sexuality. In this review, we focus on research that emerged in the near decade since PrEP's approval, with a specific focus on the ways in which different elements of sex and sexuality have been impacted by gay, bisexual, and other men who have sex with men (GBMSM), cisgender women, and transgender individuals. We highlight evidence showing how PrEP has enhanced sexual self-esteem, improved sexual pleasure, reduced sexual anxiety, and has increased sexual agency for those taking it. For many, PrEP also serves as a gateway to improve routine health and increase sexual health-care utilization. Additionally, we review the question of whether PrEP is associated with increased sexual risk taking (i.e. risk compensation), and note that, although some data are mixed, PrEP is not intended as an intervention to reduce condomless anal sex or STIs: it aims to prevent HIV. Finally, our review highlights that, although the volume of research on PrEP among GBMSM is robust, it is underdeveloped for cisgender women and transgender populations and insufficient for inclusion in such a review for cisgender heterosexual men was. PrEP research with these populations is an important direction for future research. Finally, from 2012 to 2019, a single PrEP formulation and delivery method was FDA approved (oral emtricitabine/tenofovir disoproxil fumarate). As additional drug formulations (ie.g., emtricitabine/tenofovir alafenamide) and delivery methods (e.g., microbiocides, vaginal ring, injectable) come to market, it will be important to examine how these, too, impact the spectrum of sexuality.

Barriers and Facilitators to Pre-exposure Prophylaxis Uptake Among Black Women: A Qualitative Analysis Guided by a Socioecological Model.

ABSTRACT: Black women experience disparities in HIV incidence. Pre-exposure prophylaxis (PrEP) is a once-daily pill that can prevent HIV transmission. To enhance PrEP uptake among Black women, it is essential to examine their perceptions of PrEP. In 2018, 33 Black women in New York City completed interviews about their attitudes, knowledge, and perceived barriers and facilitators to PrEP use. Emergent themes were organized using a socioecological model. Participants identified barriers at the sociocultural level, including stigma, medical mistrust, and health care avoidance. At the community level, health care access issues and limited community knowledge were reported. Partner-level barriers included trust in partners and meaning attributed to PrEP use within the context of monogamy. Individual-level barriers included low perceived risk and concerns about PrEP's safety and efficacy. Our findings can inform future PrEP research with Black women, as well as PrEP implementation efforts aimed at increasing uptake among this population.

Breaking Bad Patents: Learning from HIV/AIDS to make COVID-19 treatments accessible.

The COVID-19 pandemic has brought renewed attention to the topic of challenging drug patents in the interest of public health. Pharmaceutical companies have already begun to patent existing medicines for the treatment and prevention of SARS-CoV-2, affording them exclusive manufacturing rights over vital medicines. Advocates have raised concerns regarding the pricing of COVID-19 drugs, as well as patent monopolies on the manufacture of COVID-19 treatments. The HIV/AIDS pandemic provides a useful lens through which we can analyse existing pathways for challenging pharmaceutical patents in the context of global pandemic. In this article, we review three legal pathways for overriding and seizing patents on medicines by describing cases in which they were employed to make antiretroviral drugs more accessible to people living with HIV. Last, we highlight the weaknesses inherent in these pathways and offer advocacy and policy suggestions for how to strengthen these pathways to improve access to COVID-19 treatments as they become available in the United States and globally.

Marketing of Tenofovir Disoproxil Fumarate (TDF) Lawsuits and Social Media Misinformation Campaigns' Impact on PrEP Uptake Among Gender and Sexual Minority Individuals.

There has been an influx of ads on social media seeking plaintiffs in lawsuits for harms/side-effects caused by tenofovir disoproxil fumarate/Emtricitabine (TDF/FTC, Truvada) for PrEP. Community groups and researchers have suggested these ads may be undermining efforts to disseminate PrEP to key populations. In October 2019, we began assessing the impact of injury lawsuit ads on social media platforms in an ongoing U.S. national cohort study of HIV-negative cis men, trans men, and trans women who have sex with men. Although assessments are ongoing, given the alarming nature of our findings, we report data collected as of March 2020 (n = 2078). Most (59.9%) said they had seen ads for TDF-related lawsuits on social media. Twenty-eight percent said they would probably or definitely not start PrEP and 22.1% said they would not stay on PrEP (were they on it) as a result of seeing these ads. Next, 38.2% agreed or strongly agreed that seeing these ads made them think that TDF/FTC for PrEP was not safe. Black, Latinx, and/or multiracial individuals were most likely to be negatively impacted by the ads including perceptions that these ads made them think PrEP is not safe. In contrast, past year experience taking PrEP was positively associated with intentions to start and/or stay on PrEP despite seeing the ads. Due to forthcoming affordable/generic options, TDF/FTC is projected to become the most scalable option for disseminating PrEP to key populations. Results suggest that ads for TDF lawsuits on social media are having a negative impact on individual PrEP decision-making. Our findings highlight the urgency for accurate and balanced messaging on the benefits and risks of PrEP, so that individuals can make informed choices about whether PrEP is right for them.

Experiences Receiving HIV-Positive Results by Phone: Acceptability and Implications for Clinical and Behavioral Research.

Improving HIV testing rates and increasing early detection among men who have sex with men (MSM) are critical strategies for enhancing overall health and decreasing HIV transmission. Remote testing and phone delivery of HIV test results may reduce barriers such as geographic isolation or HIV-related stigma. In 2018-19, 50 MSM completed qualitative interviews about their experience receiving a positive HIV test result via phone through their participation in a research study that included remote HIV testing. Interview topics included the acceptability of, and concerns about, phone delivery of HIV results, as well as suggestions for improvement. Interviews were transcribed, coded, and analysed using an inductive thematic approach. Overall, participants reported high acceptability of phone delivery of HIV-positive results. Participants praised the support and information provided by study staff. Benefits identified included increased convenience compared to in-person medical visits, allowing participants to emotionally process their test results privately, as well as receiving the results from supportive and responsive staff members. A few participants indicated drawbacks to phone-based HIV test result delivery, such as logistical concerns about receiving a phone call during the day (e.g., while at work), reduced confidentiality, and the lack of in-person emotional support. Overall, participants described phone delivery of positive HIV-results as acceptable. At-home testing with phone delivery has the potential to increase HIV testing access, especially to geographically isolated or medically underserved patients.

Insurance- and medical provider-related barriers and facilitators to staying on PrEP: results from a qualitative study.

Pre-exposure prophylaxis (PrEP) is a highly effective biobehavioral strategy for preventing HIV acquisition. Although PrEP uptake has increased steadily, discontinuation rates are high among members of key populations like gay and bisexual men (GBM). Understanding the challenges that arise for PrEP users is key to better PrEP implementation and sustained use over time. We report on barriers that arose for PrEP-using GBM, as well as facilitating factors that aided PrEP persistence, with the goal of informing PrEP implementation efforts. In 2015-2016, 103 PrEP-using GBM in NYC completed qualitative interviews about their engagement with PrEP, including their experiences navigating PrEP-related medical care. Interviews were transcribed verbatim, coded, and analyzed thematically. Over half of participants (53%) received their PrEP-related care from their primary care provider (PCP), one-third (33%) from a community-based health clinic, and 13% from multiple medical providers. Emergent themes regarding the barriers and facilitators to PrEP persistence fell into two categories: insurance- and medical appointment-related barriers and facilitators to continued PrEP use. The experiences of PrEP-using GBM can provide useful insights for providers, program developers, and policymakers aiming to improve the implementation of PrEP. To support PrEP persistence, reliable insurance coverage, cost-assistance, and easy appointment scheduling are key to maintenance. Removing insurance- and appointment-related barriers to persistence may prove essential for sustaining use among GBM.

Sociocultural influences on attitudes towards pre-exposure prophylaxis (PrEP), history of PrEP use, and future PrEP use in HIV-vulnerable cisgender men who have sex with men across the U.S.

Despite its proven effectiveness in reducing HIV transmission, pre-exposure prophylaxis (PrEP) use remains low. This study used data from a 2017-2018 U.S. national cohort to investigate social influences on PrEP experience and future PrEP use among cisgender men who have sex with men. We used descriptive statistics and multivariable logistic analyses to examine social influences (e.g., how participants heard about PrEP and number of persons they knew taking PrEP) associated with each previous PrEP use and intentions to use PrEP. Among participants who knew of PrEP, commonly reported ways of first hearing about PrEP were through social media (27.4%) and friends (26.8%). These were also cited top influences on participants' current attitudes toward PrEP (friends 23.5%, social media 22.1%). Multivariable logistic regression analyses found that knowing more people taking PrEP was associated with increased odds of previously using PrEP and intending to use PrEP. Friends and social media were common and influential sources of information regarding PrEP. Results suggest that tapping into these social connections may effectively disseminate public health messaging about PrEP and encourage use among key populations to reduce HIV burden.

A Web-Based Study of HIV Prevention in the Era of Pre-Exposure Prophylaxis Among Vulnerable HIV-Negative Gay and Bisexual Men, Transmen, and Transwomen Who Have Sex With Men: Protocol for an Observational Cohort Study.

BACKGROUND: Gay, bisexual, and other men who have sex with men continue to bear a large burden of the HIV epidemic in the United States and are among the only populations with increasing incidence in recent years. OBJECTIVE: The Together 5000 (T5K) Study aimed to enroll a US-based, racially diverse sample of HIV-negative men, transmen, and transwomen who are not on pre-exposure prophylaxis (PrEP) into an observational cohort to inform the design, implementation, scale-up, and evaluation of HIV prevention programs. METHODS: We used internet-based strategies to enroll a large, racially diverse national sample of HIV-negative men, transmen, and transwomen aged 16 to 49 years at high risk of HIV acquisition via sexual networking apps. Study participants are contacted every 6 months (in between annual surveys) for a brief survey on HIV testing, HIV diagnosis, and PrEP use (ie, attempts to access, PrEP initiation, and PrEP discontinuation). Participants complete annual self-administered at-home HIV testing and Web-based surveys. Using baseline serologic data and self-reported HIV testing history, we reconstructed a cohort of persons who were HIV negative at 12 months before baseline to estimate HIV incidence leading up to cohort enrollment. RESULTS: The study sample included 8777 participants from all 50 US states, Puerto Rico, and Guam; 50.91% (4468/8777) were persons of color and 25.30% (2221/8777) were young individuals aged 16 to 24 years. Per eligibility criteria, all T5K participants reported having sex with >2 male partners in the 90 days before enrollment, self-reported not having been diagnosed with HIV, and were not actively taking PrEP. In addition, 79.39% (6968/8777) reported >2 insertive condomless anal sex (CAS) acts, 61.02% (5356/8777) reported >1 receptive CAS acts in the past 90 days. Furthermore, most (7525/8777, 85.74%) reported never having taken PrEP. In total, 70.25% (6166/8777) were sent a self-administered at-home HIV test kit and 82.29% (5074/6166) of those sent a kit returned a sample for testing. The HIV incidence rate during the 12-month period leading up to enrollment was estimated to be 2.41 (95% CI 2.02-2.90) per 100 person-years. CONCLUSIONS: A large, national, and racially diverse fully Web-based cohort of HIV-negative men, transmen, and transwomen at high risk for HIV seroconversion has successfully been recruited into longitudinal follow-up. This cohort is at high risk for HIV acquisition and can provide important insights related to the real-world uptake, impact, and equity of HIV prevention interventions in the United States. Participants can be invited to participate in trials aimed at testing strategies to improve the uptake of and engagement in these interventions. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/13715.