Asymptomatic Rectal Bacterial Pathogens Show Large Prospective Relationships With HIV Incidence in a Cohort of Young Sexual and Gender Minorities: Implications for STI Screening and HIV Prevention.

Background: We estimated the predictive value of rectal (bacterial sexually transmitted infection [bSTI]) pathogen detection for future HIV seroconversion among young adult sexual and gender minorities (YSGMs) assigned male at birth (AMAB). Methods: Data were collected between March 2018 and August 2022 from RADAR, a longitudinal cohort study of YSGMs AMAB living in the Chicago metropolitan area (n = 1022). Rates of rectal bSTIs and the proportion of self-reported rectal bSTI symptoms are reported. We examined whether the presence of rectal bSTIs predicted HIV seroconversion using generalized estimating equations (GEEs). Results: Participants tested reactive for rectal Mycoplasma genitalium (MGen), Neisseria gonorrhoeae (NG), and Chlamydia trachomatis (CT) at a rate of 20.8 (95% CI, 18.4-23.5), 6.5 (95% CI, 5.0-8.2), and 8.4 (95% CI, 6.8-10.3) cases per 100 persons, respectively. There were no statistically significant pairwise differences in self-reported rectal bSTI symptoms between participants with self-collected swabs testing nonreactive vs reactive for rectal MGen (χ2 = 0.04; P = .84), NG (χ2 = 0.45; P = .37), or CT (χ2 = 0.39; P = .46). In multivariate GEE analysis, rectal NG (adjusted odds ratio, 5.11; 95% CI, 1.20-21.77) was a statistically significant predictor of HIV seroconversion after controlling for other bSTIs, demographics, and sexual risk behavior. Conclusions: Our findings provide a robust longitudinal estimation of the relationship between primarily asymptomatic rectal NG nucleic acid detection and HIV infection. These findings highlight the importance of asymptomatic screening for bSTIs and targeting biobehavioral intervention to prevent HIV infection among YSGMs with rectal bSTI agents detected.

Urine point-of-care tenofovir test demonstrates strong predictive clinical and research utility.

BACKGROUND: Preexposure prophylaxis (PrEP) significantly reduces HIV infection risk but is dependent on adherence. Available approaches to measuring adherence have limitations related to accuracy, cost, practicality, and timeliness. This study compared the performance of two methods implementable in clinics and research studies [interview and urine point of care (POC) assay] to the gold-standard for measuring recent and longer term adherence in dried blood spots (DBS). METHODS: Participants were recruited from RADAR, a cohort study of young MSM, or via online advertisements. At 3 monthly visits, an interviewer administered 7-day timeline follow-back (TLFB) questionnaire, DBS samples were tested for tenofovir-diphosphate (TFV-DP) to estimate average dosing over the prior month and emtricitabine-triphosphate (FTC-TP) to assess recent dosing (past 2-3 days), and a urine POC TFV test to qualitatively assess recent adherence (past 4 days). RESULTS: Eighty-three PrEP users contributed 163 observations. At visit 1, self-reported adherence was 86% (4+ doses in last 7 days), versus urine TFV (74%), DBS FTC-TP (76%), and DBS TFV-DP (69%). The objective measures of short-term adherence performed similarly well in predicting longer term adherence. In multivariable logistic regression analyses, the urine assay was a significant predictor of DBS TFV-DP (adjusted OR = 19.4, P  < 0.0001); self-report did not add significantly. CONCLUSION: The urine POC TFV assay had excellent predictive values for adherence and self-report did not add significantly to prediction. The POC assay provides results in several minutes to enable same-visit counseling, requires no specialized training, and is projected to be low-cost.

The Sexual Orientation Microaggression Inventory Short Form (SOMI-SF): Validation in Three Samples of Racially/Ethnically Diverse Sexual Minority Youth.

Introduction: The Sexual Orientation Microaggression Inventory (SOMI) has been used to measure sexual orientation-based microaggression experiences. However, at 19 items, the SOMI may be difficult to fit into survey batteries where microaggressions are not the primary predictor or the time researchers have with each participant is very limited. Methods: We sought to identify an eight-item short form of the SOMI (SOMI-SF) in a sample of sexual minority (SM) youth (N = 879) and confirm the validity and reliability of the SOMI-SF by administering both versions to separate cohorts of male-assigned (N = 533) and female-assigned (N = 430) at birth SM youth. Data was collected from April 2018 to May 2020. Results: We found high reliability (α > 0.80) and validity (significant association with SM victimization, depression symptoms, anxiety symptoms, and internalized stigma) in all three samples for the SOMI-SF. Conclusions: For researchers looking to conserve time and limit burden, the SOMI-SF is a high quality option for measuring sexual orientation microaggressions. Policy Implications: The greater ease of administering the SOMI-SF means that sexual orientation microaggressions can be measured in a greater number of contexts. With a growing literature linking these experiences to poorer health outcomes for SM populations, measuring these experiences quickly and accurately can improve our understanding of the mechanisms creating those links and impact policy necessary to alleviate them.

Stress and Depression Are Associated with Sexual Function and Satisfaction in Young Men Who Have Sex with Men.

Prior research suggests that better mental health and higher relationship quality are associated with better sexual function and satisfaction. Such insights can inform intervention development for mental, relationship, and sexual health concerns. This study examined the interactions among these variables in a racially and ethnically diverse group of young men who have sex with men (YMSM) in serious relationships (N = 348). Data were drawn from wave 5 of a longitudinal cohort study. We examined cross-sectional associations between depression and stress (predictors) and sexual function, sexual satisfaction, and anal discomfort (outcomes) and to what extent these associations were moderated by relationship quality. Higher endorsement of depression and stress was associated with worse sexual functioning, lower sexual satisfaction, and more anal discomfort. We also found that fewer negative interactions, stronger commitment, and higher relationship satisfaction were associated with better sexual functioning and higher sexual satisfaction. Higher relationship satisfaction and commitment were found to attenuate the association between stress and sexual satisfaction. Contrary to expectations, higher relationship satisfaction also showed a trend toward exacerbating the association between depression and sexual functioning. These results suggest that, for YMSM, high relationship satisfaction and commitment may protect sexual satisfaction from being negatively impacted by high stress. However, YMSM in highly satisfying relationships may experience poor sexual functioning associated with depression as particularly distressing. This study addressed a major gap in the literature by focusing on mental, relationship, and sexual health in a diverse sample. Future research should examine a wider range of sexual functioning outcomes and include minority stress in study design.

COVID-19 symptom severity predicts neutralizing antibody activity in a community-based serological study.

Serological testing for SARS-CoV-2 IgG antibodies is used to assess their presence in blood samples from exposed individuals and provides a measure of the magnitude of immune response to infection. The measurement of neutralizing antibodies (NAbs) in particular provides information about the severity of prior infection and level of protective immunity against re-infection. Much of the work investigating the association between prior infection severity and NAb levels has been conducted among clinical populations, and less is known about this relationship in the general population. Accordingly, we utilize data from a large (n = 790) community-based cohort of unvaccinated, seropositive participants. We analyzed the association between NAb response, measured via surrogate virus neutralization assay, with patterns of symptoms and household exposure. Our results indicate no detectable NAb activity in 63.8% of the seropositive participants (n = 504). Those with detectable NAb levels demonstrated a positive relationship between NAb activity and both self-reported previous symptom severity and household exposure. These findings are significant in light of recent concerns about degree of protective immunity conferred by prior infection or vaccination, and we highlight the value of community-based research for investigating variation in immune response.

Low Levels of Neutralizing Antibodies After Natural Infection With Severe Acute Respiratory Syndrome Coronavirus 2 in a Community-Based Serological Study.

BACKGROUND: Confidence in natural immunity after infection with severe acute respiratory syndrome coronavirus 2 is one reason for vaccine hesitancy. METHODS: We measured antibody-mediated neutralization of spike protein-ACE2 receptor binding in a large community-based sample of seropositive individuals who differed in severity of infection (N = 790). RESULTS: A total of 39.8% of infections were asymptomatic, 46.5% were symptomatic with no clinical care, 13.8% were symptomatic with clinical care, and 3.7% required hospitalization. Moderate/high neutralizing activity was present after 41.3% of clinically managed infections, in comparison with 7.9% of symptomatic and 1.9% of asymptomatic infections. CONCLUSIONS: Prior coronavirus disease 2019 infection does not guarantee a high level of antibody-mediated protection against reinfection in the general population.

mRNA intramuscular vaccination produces a robust IgG antibody response in advanced neuromuscular disease.

SARS-CoV-2 vaccines protect against symptomatic and severe COVID-19. The BNT162b2/Pfizer and mRNA-1273/Moderna vaccines represent new vaccine technology relying on administration of mRNA encoding SARS-CoV-2 viral spike protein encased in lipid nanoparticles. The vaccines are administered as two doses into muscle, which elicits a strong response, typically within 14 days after the second dose. Neuromuscular diseases are characterized by the progressive loss of muscle and are often treated with chronic glucocorticoid steroids, both of which may contribute to a blunted immune response to vaccination. Here, we measured IgG antibody content and neutralizing antibody response after mRNA COVID-19 vaccination in non-ambulatory neuromuscular disease patients. After two doses of mRNA COVID-19 vaccine, median anti-receptor binding domain IgG and percent surrogate viral neutralization in non-ambulatory neuromuscular disease samples were significantly elevated similar to healthy vaccinated controls. As in healthy controls, COVID-19 vaccines produce greater antibody levels compared to those with a history of outpatient COVID-19 infection. This data documents that non-ambulatory neuromuscular disease patients respond well to two doses of mRNA COVID-19 vaccine despite low muscle mass and even chronic steroid use.

Geographic disparities in COVID-19 case rates are not reflected in seropositivity rates using a neighborhood survey in Chicago.

To date, COVID-19 case rates are disproportionately higher in Black and Latinx communities across the US, leading to more hospitalizations, and deaths in those communities. These differences in case rates are evident in comparisons of Chicago neighborhoods with differing race and/or ethnicities of their residents. Disparities could be due to neighborhoods with more adverse health outcomes associated with poverty and other social determinants of health experiencing higher prevalence of SARS-CoV-2 infection or due to greater morbidity and mortality resulting from equivalent SARS-CoV-2 infection prevalence. We surveyed five pairs of adjacent ZIP codes in Chicago with disparate COVID-19 case rates for highly specific and quantitative serologic evidence of any prior infection by SARS-CoV-2 to compare with their disparate COVID-19 case rates. Dried blood spot samples were self-collected at home by internet-recruited participants in summer 2020, shortly after Chicago's first wave of the COVID-19 pandemic. Pairs of neighboring ZIP codes with very different COVID-19 case rates had similar seropositivity rates for anti-SARS-CoV-2 receptor binding domain IgG antibodies. Overall, these findings of comparable exposure to SARS-CoV-2 across neighborhoods with very disparate COVID-19 case rates are consistent with social determinants of health, and the co-morbidities related to them, driving differences in COVID-19 rates across neighborhoods.

Cohabitation With a Known Coronavirus Disease 2019 Case Is Associated With Greater Antibody Concentration and Symptom Severity in a Community-Based Sample of Seropositive Adults.

In a community-based sample of seropositive adults (n = 1101), we found that seropositive individuals who lived with a known coronavirus disease 2019 (COVID-19) case exhibited higher blood anti-severe acute respiratory syndrome coronavirus 2 spike receptor-binding domain immunoglobulin G concentrations and greater symptom severity compared to seropositive individuals who did not live with a known COVID-19 case.

Comparison of IgG and neutralizing antibody responses after one or two doses of COVID-19 mRNA vaccine in previously infected and uninfected individuals.

BACKGROUND: Recent reports have suggested that among individuals previously infected with SARS-CoV-2, a single mRNA vaccine dose is sufficient to elicit high levels of immunity. METHODS: We compared anti-SARS-CoV-2 spike receptor binding domain (RBD) IgG antibody concentrations and antibody-mediated neutralization of spike-angiotensin-converting enzyme (ACE2) receptor binding in vitro following vaccination of non-hospitalized participants by sero-status and acute virus diagnosis history. Participants were analysed before and after mRNA vaccination (BNT162b2/Pfizer or mRNA-1273/Moderna) in a community-based, home-collected, longitudinal serosurvey in the Chicago area (USA); none reported hospitalization for COVID-19. Samples were collected in January and February 2021. Before vaccination, some reported prior positive acute viral diagnostic testing and were seropositive (COVID-19+); the others who did not report acute viral diagnostic testing were categorized as seropositive or seronegative based on anti-spike RBD IgG test results. FINDINGS: Of 307 unique vaccine recipients, 46 reported a prior COVID-19 diagnosis and were seropositive (COVID-19 +). Of the 261 with no history of acute viral diagnostic testing, 117 were seropositive and 144 seronegative before vaccination. The median age was 38 years (range 21-83) with 67 female and 33% male; 40% were non-White. Responses were evaluated after one (n = 142) or two (n = 191) doses of BNT162b2 or mRNA-1273 vaccine. After one dose, median post-vaccine IgG concentration and percent surrogate neutralization were each significantly higher among the COVID-19+ (median 48·2 µg/ml, IgG; > 99.9% neutralization) compared to the seropositives (3·6 µg /ml IgG; 56.5% neutralization) and seronegatives (2·6 µg /ml IgG; 38·3% neutralization). The latter two groups reached > 95% neutralization after the second vaccine dose. INTERPRETATION: After one dose of mRNA vaccine, individuals previously diagnosed with COVID-19 responded with high levels of anti-RBD IgG and surrogate neutralization of spike-ACE2 interaction. One dose of mRNA vaccine was not sufficient to generate comparably high responses among most persons previously infected with SARS-CoV-2 without a clinical COVID-19 diagnosis, nor among seronegative persons. FUNDING: National Science Foundation 2035114, NIH 3UL1TR001422-06S4, and Northwestern University Office of Research.

COVID-19 mRNA Vaccination Generates Greater Immunoglobulin G Levels in Women Compared to Men.

We investigated whether the antibody response to coronavirus disease 2019 (COVID-19) mRNA vaccination is similar in women and men. In a community cohort without prior COVID-19, first vaccine dose produced higher immunoglobulin G (IgG) levels and percent inhibition of spike-ACE2 receptor binding, a surrogate measure of virus neutralization, in women compared to men (7.0 µg/mL, 51.6% vs 3.3 µg/mL, 36.4%). After 2 doses, IgG levels remained significantly higher for women (30.4 µg/mL) compared to men (20.6 µg/mL), while percent inhibition was similar (98.4% vs 97.7%). Sex-specific antibody response to mRNA vaccination informs future efforts to understand vaccine protection and side effects.

Predicting suicidality using a computer adaptive test: Two longitudinal studies of sexual and gender minority youth.

OBJECTIVE: Over the past decade, rates of death by suicide have increased among youth. Efficient and effective screening approaches are needed for suicide prevention. Sexual and gender minority youth (SGMY) experience profound disparities, but little is known about subgroups and risk assessments need to be validated. This study tested the psychometric properties and predictive value of a highly efficient computerized adaptive test for suicide risk (CAT-SS) among SGMY. METHODS: Participants in two cohort studies of SGMY completed the CAT-SS and validated measures of suicidality in 2018 (n = 1,073) and at their follow-up visit 6 months later (n = 936). Tests of psychometrics and predictive validity were performed. RESULTS: Younger, assigned female at birth, nonmonosexual (e.g., bisexual; relative to monosexual), and gender nonconforming or nongender binary (relative to cisgender and transgender) participants had significantly higher CAT-SS scores. None of the CAT-SS items met the threshold for differential item functioning. In longitudinal analyses, prediction of suicidality moved from poor to good accuracy once CAT-SS was included in the model. CAT-SS significantly improved prediction of suicidality over-and-above reported suicidality at a prior wave. CONCLUSIONS: The current study validated CAT-SS as a brief predictor of suicide risk in the disproportionately affected population of SGMY. Screening of SGMY in clinical and community settings using CAT-SS could allow for the identification of participants that need services to reduce their risk of future suicide. Results support the need for particular attention to suicide prevention among SGMY who are teenagers, assigned female at birth, nonmonosexual, and gender nonconforming or nongender binary. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Exposure to SARS-CoV-2 within the household is associated with greater symptom severity and stronger antibody responses in a community-based sample of seropositive adults.

Magnitude of SARS-CoV-2 virus exposure may contribute to symptom severity. In a sample of seropositive adults (n=1101), we found that individuals who lived with a known COVID-19 case exhibited greater symptom severity and IgG concentrations compared to individuals who were seropositive but did not live with a known case (P<0.0001).

Patterns and persistence of SARS-CoV-2 IgG antibodies in Chicago to monitor COVID-19 exposure.

BACKGROUNDEstimates of seroprevalence to SARS-CoV-2 vary widely and may influence vaccination response. We ascertained IgG levels across a single US metropolitan site, Chicago, from June 2020 through December 2020.METHODSParticipants (n = 7935) were recruited through electronic advertising and received materials for a self-sampled dried-blood spot assay through the mail or a minimal contact in-person method. IgG against the receptor-binding domain of SARS-CoV-2 was measured using an established highly sensitive and highly specific assay.RESULTSOverall seroprevalence was 17.9%, with no significant difference between method of contact. Only 2.5% of participants reported having had a diagnosis of COVID-19 based on virus detection, consistent with a 7-fold greater exposure to SARS-CoV-2 measured by serology than that detected by viral testing. The range of IgG level observed in seropositive participants from this community survey overlapped with the range of IgG levels associated with COVID-19 cases having a documented positive PCR test. From a subset of those who participated in repeat testing, half of seropositive individuals retained detectable antibodies for 3 to 4 months.CONCLUSIONQuantitative IgG measurements with a highly specific and sensitive assay indicated more widespread exposure to SARS-CoV-2 than observed by viral testing. The range of IgG concentrations produced from these asymptomatic exposures was similar to IgG levels occurring after documented nonhospitalized COVID-19, which were considerably lower than those produced from hospitalized COVID-19 cases. The differing ranges of IgG response, coupled with the rate of decay of antibodies, may influence response to subsequent viral exposure and vaccine.FundingNational Science Foundation grant 2035114, NIH grant 3UL1TR001422-06S4, NIH National Center for Advancing Translational Sciences grants UL1 TR001422 and UL1 TR002389, Dixon Family Foundation, Northwestern University Cancer Center (NIH grant P30 CA060553), and Walder Foundation's Chicago Coronavirus Assessment Network.

Patterns and persistence of SARS-CoV-2 IgG antibodies in Chicago to monitor COVID-19 exposure.

Background: Estimates of seroprevalence to SARS-CoV-2 vary widely and may influence vaccination response. We ascertained IgG levels across a single US metropolitan site, Chicago, from June 2020 through December 2020. Methods: Participants (n=7935) were recruited through electronic advertising and received materials for a self-sampled dried blood spot assay through the mail or a minimal contact in person method. IgG to the receptor binding domain of SARS-CoV-2 was measured using an established highly sensitive and highly specific assay. Results: Overall seroprevalence was 17.9%, with no significant difference between method of contact. Only 2.5% of participants reported having had a diagnosis of COVID-19 based on virus detection, consistent with a 7-fold greater exposure to SARS-CoV-2 measured by serology than detected by viral testing. The range of IgG level observed in seropositive participants from this community survey overlapped with the range of IgG levels associated with COVID-19 cases having a documented positive PCR positive test. From a subset of those who participated in repeat testing, half of seropositive individuals retained detectable antibodies for 3-4 months. Conclusions: Quantitative IgG measurements with a highly specific and sensitive assay indicate more widespread exposure to SARS-CoV-2 than observed by viral testing. The range of IgG concentration produced from these asymptomatic exposures is similar to IgG levels occurring after documented non-hospitalized COVID-19, which is considerably lower than that produced from hospitalized COVID-19 cases. The differing ranges of IgG response, coupled with the rate of decay of antibodies, may influence response to subsequent viral exposure and vaccine.

High Burden of Mental Health Problems, Substance Use, Violence, and Related Psychosocial Factors in Transgender, Non-Binary, and Gender Diverse Youth and Young Adults.

Transgender and gender diverse (TGD) people are disproportionately impacted by various health issues and associated risk factors, but little is known about differences in these outcomes between gender identities within the TGD population. This study characterized the health of a diverse sample of TGD youth and young adults. Data were taken from the baseline visit of two longitudinal studies in the Chicago area, RADAR (N = 1079, M age = 20.8 years) and FAB 400 (N = 488, M age = 19.57 years), which are cohorts of young sexual and gender minorities assigned male at birth (AMAB) and assigned female at birth (AFAB), respectively. There was a combined sample of 214 TGD (128 AFAB, 86 AMAB) individuals across cohorts. We examined differences between gender identities in self-reported health and related psychosocial variables, and compared TGD youth and their cisgender sexual minority peers from their cohort of origin on all variables. Among TGD youth, we found high rates of depression and suicidality (ideation, plan, attempt), violence (trauma, victimization, childhood sexual abuse), and substance use (cigarette, alcohol, illicit drug use). With the exception of depression, transgender women and non-binary AMAB youth reported worse health outcomes than transgender men and non-binary AFAB youth. Non-binary AMAB youth reported the highest rates of certain outcomes, including traumatic experiences and suicidal ideation. TGD youth generally reported worse outcomes than cisgender sexual minority youth; these differences were less pronounced among AFAB youth. Findings point to the diversity of experiences within the TGD population and critical needs for intervention approaches to mitigate health disparities.

Very High HIV Incidence and Associated Risk Factors in a Longitudinal Cohort Study of Diverse Adolescent and Young Adult Men Who Have Sex with Men and Transgender Women.

To report HIV incidence and associated factors among young men who have sex with men (YMSM) and transgender women (TW). Data were collected February 2015 to July 2018 in the RADAR longitudinal cohort study of YMSM/TW aged 16-29 years (N = 1093). Data included tests for HIV and rectal STIs and self-reported sexual behaviors and networks characteristics. HIV incidence rates were 2.91 per 100 person years (44 seroconversions among 1513 person years). Incidence was significantly higher in Black participants than white (IRR 8.81; 95% CI 2.72-45.26) and Latinx (IRR 3.15; 1.49-7.28) participants, but no significant differences by gender identity were found. Testing positive for rectal STIs (HR 2.50; 95% CI 1.27-4.92) and sex with a partner from a high HIV incidence community area (HR 2.46; 95% CI 1.19-5.07) were associated with higher incidence. HIV incidence was very high and Black YMSM/TW experienced higher HIV incidence attributable to partner race and geographic residence. Rectal STIs were associated with increased HIV incidence.

High Rate of Discontinuation May Diminish PrEP Coverage Among Young Men Who Have Sex with Men.

Understanding pre-exposure prophylaxis (PrEP) discontinuation is key to maximizing its effectiveness at the individual and population levels. Data came from the RADAR cohort study of MSM aged 16-29 years, 2015-2017. Participants included those who reported past 6-month PrEP use and discontinued its use by the interview date. Of the 197 participants who had used PrEP in the past 6 months, 65 discontinued use. Primary reasons for PrEP discontinuation included trouble getting to doctor's appointments (14, 21.5%) and issues related to insurance coverage or loss (13, 20.0%). Few (21%) who discontinued spoke to their doctor first, which has important implications for future long acting formulations.

Threefold Increase in PrEP Uptake Over Time with High Adherence Among Young Men Who Have Sex With Men in Chicago.

The goal of this work is to better understand utilization and uptake of pre-exposure prophylaxis (PrEP) among young men who have sex with men (YMSM) and transgender women (TGW). We assessed trends and correlates of PrEP use and adherence across three time points of longitudinal data collection among 885 YMSM and TGW (aged 16-29) from the RADAR cohort in Chicago, 2015-2017. Past 6-month PrEP use increased across three visits: from 6.6 to 17.5%. In multivariable models, past 6-month PrEP use was significantly associated with participation in condomless sex, having more sexual partners, and older age. At least three-quarters of current PrEP users reported being ≥ 90% adherent to PrEP medication across all visits. Past 6-month PrEP use increased over time with those who participated in high-risk HIV behaviors also those most likely to have taken PrEP. As PrEP uptake continues to rise, more research will be needed to understand predictors of PrEP usage, as well as patterns of sexual behavior change following uptake.

Geographic and Individual Associations with PrEP Stigma: Results from the RADAR Cohort of Diverse Young Men Who have Sex with Men and Transgender Women.

Increasing the uptake of pre-exposure prophylaxis (PrEP) to prevent HIV acquisition among at-risk populations, such as young men who have sex with men (YMSM), is of vital importance to slowing the HIV epidemic. Stigma and negative injunctive norms, such as the so called "Truvada Whore" phenomenon, hamper this effort. We examined the prevalence and types of PrEP stigma and injunctive norm beliefs among YMSM and transgender women and associated individual and geospatial factors. A newly created measure of PrEP Stigma and Positive Attitudes was administered to 620 participants in an ongoing longitudinal cohort study. Results indicated lower stigma among White, compared to Black and Latino participants, and among participants not identifying as male. Prior knowledge about PrEP was associated with lower stigma and higher positive attitudes. PrEP stigma had significant geospatial clustering and hotspots were identified in neighborhoods with high HIV incidence and concentration of racial minorities, whereas coldspots were identified in areas with high HIV incidence and low LGBT stigma. These results provide important information about PrEP attitudes and how PrEP stigma differs between individuals and across communities.