Sexual network characteristics, condomless anal intercourse, and the HIV care cascade among MSM living with controlled versus uncontrolled HIV infection in Lima, Peru: a population-based cross-sectional analysis.

Background: Despite high rates of HIV transmission among men who have sex with men (MSM) in Lima, Peru, limited data exist on the sexual network characteristics or risk factors for secondary HIV transmission among MSM with uncontrolled HIV infection. We report the frequency of serodiscordant, condomless anal intercourse (CAI) and associated sexual network characteristics among MSM in Lima with detectable HIV viremia and compare to those with undetectable viremia. Methods: This cross-sectional analysis includes MSM who tested positive for HIV-1 during screening for a trial of partner management and STI control (June 2022-January 2023). Participants were tested for HIV, gonorrhoea, chlamydia, and syphilis, and completed questionnaires on their demographic characteristics, sexual identity and behaviour, sexual network structures and engagement in HIV care. Findings: Of 665 MSM, 153 (23%) had detectable (>200 copies/mL) viremia. 75% (499/662) of men living with HIV were previously diagnosed, with 94% (n = 469/499) reporting that they were on ART, and 93% (n = 436/469) virally suppressed. 96% (n = 147/153) of men with detectable viremia reported serodiscordant CAI with at least one of their last three sexual partners, and 74% (n = 106/144) reported the same with all three of their recent partners. In contrast, 62% (n = 302/489) of men with undetectable viral load reported serodiscordant CAI with all of their last three partners (p < 0.01). Interpretation: 23% of men living with HIV in Peru had detectable viremia, of whom almost all (96%) reported recent serodiscordant CAI. The primary gap in the HIV care cascade lies in awareness of HIV serostatus, suggesting that improved access to HIV testing could be a key prevention strategy in Peru. Funding: Funding for this study was provided by NIH/NIMH grants R01 MH118973 (PI: Clark) and R25 MH087222 (PI: Clark).

Changes in Inflammatory Cytokine Levels in Rectal Mucosa Associated With Neisseria gonorrheae and/or Chlamydia trachomatis Infection and Treatment Among Men Who Have Sex With Men in Lima, Peru.

BACKGROUND: Neisseria gonorrheae and Chlamydia trachomatis are associated with mucosal inflammation and human immunodeficiency virus 1 (HIV-1) transmission. We assessed levels of inflammatory cytokines in men who have sex with men (MSM) with and without rectal gonorrhea and/or chlamydia in Lima, Peru. METHODS: We screened 605 MSM reporting condomless receptive anal intercourse for rectal N. gonorrheae/C. trachomatis using nucleic acid testing. We identified 101 cases of gonorrhea and/or chlamydia and randomly selected 50 N. gonorrheae/C. trachomatis positive cases and matched 52 negative controls. We measured levels of IL-1ß, IL-6, IL-8, and TNF-α in rectal secretions. Tests for HIV-1, rectal N. gonorrheae/C. trachomatis, and mucosal cytokines were repeated after 3 and 6 months. Cytokine levels in cases and uninfected controls were compared using Wilcoxon rank-sum tests and linear regression. RESULTS: MSM with gonorrhea/chlamydia had elevated levels of all cytokines in rectal mucosa compared with matched controls (all P values <.001). Following antibiotic treatment there were no significant differences in cytokine levels at 3- or 6-month follow-up evaluations (all P values >.05). DISCUSSION: Rectal gonorrhea/chlamydia infection is associated with transient mucosal inflammation and cytokine recruitment. Our data provide proof of concept for rectal sexually transmitted infection screening as an HIV prevention strategy for MSM. Clinical Trials Registration. NCT03010020.

Sexual network characteristics and partnership types among men who have sex with men diagnosed with syphilis, gonorrhoea and/or chlamydia in Lima, Peru.

OBJECTIVES: Sexual networks are known to structure sexually transmitted infection (STI) transmission among men who have sex with men (MSM). We sought to estimate the risks of STI diagnosis for various partnership types within these networks. METHODS: Our cross-sectional survey analysed data from 1376 MSM screened for a partner management intervention in Lima, Peru. Participants were tested for HIV, syphilis, gonorrhoea (NG) and chlamydia (CT) and completed surveys on their demographics, sexual identity/role, HIV status, partnership types and sexual network from the prior 90 days. χ2 and Wilcoxon rank-sum tests compared participants without an STI to those diagnosed with (1) syphilis, (2) NG and/or CT (NG/CT) and (3) syphilis and NG/CT coinfection (coinfection). RESULTS: 40.8% (n=561/1376) of participants were diagnosed with an STI (syphilis: 14.9%, NG/CT: 16.4%, coinfection: 9.5%). 47.9% of all participants were living with HIV and 8.9% were newly diagnosed. A greater proportion of participants with syphilis and coinfection were living with HIV (73.5%, p<0.001; 71.0%, p<0.001) compared with those with NG/CT (47.8%) or no STI (37.8%). Participants with syphilis more often reported sex-on-premises venues (SOPVs) as the location of their last sexual encounter (51.7%, p=0.038) while those with NG/CT tended to meet their last sexual partner online (72.8%, p=0.031). Respondents with coinfection were the only STI group more likely to report transactional sex than participants without an STI (31.3%, p=0.039). CONCLUSIONS: Sexual networks and partnership types of Peruvian MSM are associated with differential risks for STIs. Participants diagnosed with syphilis tended to meet single-encounter casual partners at SOPV, while MSM with NG/CT were younger and often contacted casual partners online. Coinfection had higher frequency of transactional sex. These findings suggest the potential importance of public health interventions through combined syphilis/HIV screening at SOPV, syphilis screening at routine clinic appointments for MSM living with HIV and directed advertisements and/or access to NG/CT testing through online platforms.

Both/And: Mixed methods analysis of network composition, communication patterns, and socio-economic support within social networks of transgender women involved in sex work in Lima, Peru.

INTRODUCTION: Social networks contribute to normative reinforcement of HIV prevention strategies, knowledge sharing, and social capital, but little research has characterized the social networks of transgender women (TW) in Latin America. We conducted a mixed methods analysis of three network clusters of TW in Lima, Peru, to evaluate network composition, types of support exchanged, and patterns of communication. METHODS: We recruited TW residing in or affiliated with three "casas trans" (houses shared among TW) in Lima between April-May 2018. Eligible participants were 18 or older, self-reported HIV-negative, and reported recent intercourse with a cis-male partner. Participants completed demographic questionnaires, social network interviews, and semi-structured interviews to assess egocentric network structures, support exchanged, and communication patterns. Quantitative and qualitative data were analyzed using Stata v14.1 and Atlas.ti, respectively. RESULTS: Of 20 TW, median age was 26 years and 100% reported involvement in commercial sex work. Respondents identified 161 individuals they interacted with in the past month (alters), of whom 33% were TW and 52% family members. 70% of respondents reported receiving emotional support from family, while 30% received financial support and instrumental support from family. Of the 13 (65%) respondents who nominated someone as a source of HIV prevention support (HPS), the majority (69%) nominated other TW. In a GEE regression analysis adjusted for respondent education and region of birth, being a family member was associated with lower likelihood of providing financial support (aOR 0.21, CI 0.08-0.54), instrumental support (aOR 0.16, CI 0.06-0.39), and HPS (aOR 0.18, CI 0.05-0.64). In qualitative interviews, most respondents identified a cis-female family member as their most trusted and closest network member, but other TW were more often considered sources of day-to-day support, including HPS. CONCLUSION: TW have diverse social networks where other TW are key sources of knowledge sharing and support, and family members may also represent important and influential components. Within these complex networks, TW may selectively solicit and provide support from different network alters according to specific contexts and needs. HIV prevention messaging could consider incorporating network-based interventions with TW community input and outreach efforts for supportive family members.

Both/And: Mixed methods analysis of network composition, communication patterns, and socio-economic support within social networks of transgender women in Lima, Peru.

Introduction: Social networks contribute to normative reinforcement of HIV prevention strategies, knowledge sharing, and social capital, but little research has characterized the social networks of transgender women (TW) in Latin America. We conducted a mixed methods analysis of three network clusters of TW in Lima, Peru, to evaluate network composition, types of support exchanged, and patterns of communication. Methods: We recruited TW residing in or affiliated with three "casas trans" (houses shared among TW) in Lima between April-May 2018. Eligible participants were 18 or older, self-reported HIV-negative, and reported recent intercourse with a cis-male partner. Participants completed demographic questionnaires, social network interviews, and semi-structured interviews to assess egocentric network structures, support exchanged, and communication patterns. Quantitative and qualitative data were analyzed using Stata v14.1 and Atlas.ti, respectively. Results: Of 20 TW, median age was 26 years and 100% reported involvement in commercial sex work. Respondents identified 161 individuals they interacted with in the past month (alters), of whom 33% were TW and 52% family members. 70% of respondents reported receiving emotional support from family, while 30% received financial support and instrumental support from family. Of the 13 (65%) respondents who nominated someone as a source of HIV prevention support (HPS), the majority (69%) nominated other TW. In a GEE regression analysis adjusted for respondent education and region of birth, being a family member was associated with lower likelihood of providing financial support (aOR 0.21, CI 0.08-0.54), instrumental support (aOR 0.16, CI 0.06-0.39), and HPS (aOR 0.18, CI 0.05-0.64). In qualitative interviews, most respondents identified a cis-female family member as their most trusted and closest network member, but other TW were more often considered sources of day-to-day support, including HPS. Conclusion: TW have diverse social networks where other TW are key sources of knowledge sharing and support, and family members may also represent important and influential components. Within these complex networks, TW may selectively solicit and provide support from different network alters according to specific contexts and needs. HIV prevention messaging could consider incorporating network-based interventions with TW community input and outreach efforts for supportive family members.

Gender-affirming hormone therapy decreases d-dimer but worsens insulin sensitivity in transgender women.

OBJECTIVES: Gender-affirming hormonal therapies (GAHT) and HIV increase cardiovascular risk for transgender women (TW), yet there is a paucity of data quantifying cardiometabolic changes following GAHT initiation, particularly among TW with HIV. METHODS: The Féminas study enrolled TW from October 2016 to March 2017 in Lima, Peru. Participants reported sexual activity that was high risk for HIV acquisition or transmission. All were tested for HIV/ sexually transmitted infection and were given access to GAHT (oestradiol valerate and spironolactone), HIV pre-exposure prophylaxis (PrEP) or antiretroviral therapy (ART) for 12 months. Biomarker measurement was done on stored serum, whereas fasting glucose and lipids were measured in real time. RESULTS: In all, 170 TW (32 with HIV, 138 without HIV) had median age 27 years and 70% prior GAHT use. At baseline, PCSK9, sCD14, sCD163, IL-6, sTNFRI/II, CRP and EN-RAGE levels were significantly higher in TW with HIV than in TW without HIV. High-density lipoprotein and total cholesterol were lower and insulin and glucose parameters were similar. All TW with HIV started ART, but only five achieved virological suppression at any time. No TW without HIV initiated PrEP. Over 6 months, all participants initiated GAHT and had worsening insulin, glucose and HOMA-IR. Large d-dimer decreases also occurred. Similar changes occurred in TW with and without HIV. CONCLUSIONS: In this unique cohort of TW, GAHT decreased d-dimer but worsened insulin sensitivity. Because PrEP uptake and ART adherence were very low, observed effects are primarily attributed to GAHT use. Further study is needed to better understand cardiometabolic changes in TW by HIV serostatus.

Reproductive health syndemics impact retention in care among women living with HIV in Rio de Janeiro, Brazil.

Syndemic psychosocial and reproductive factors affecting women's retention in HIV care remain understudied. We analyzed correlates of non-retention in a cohort of women with HIV in Brazil from 2000‒2015. Participants self-reported exposure to physical/sexual violence, illicit drug use, adolescent pregnancy, or induced abortion. Lifetime history of these psychosocial stressors were used to create a syndemic score based on the presence or absence of these conditions. All dichotomous variables were summed (range 0 to 4), with greater scores indicating more syndemic factors experienced. Logistic regression models identified predictors of non-retention, defined as < 2 HIV viral load or CD4 results within the first year of enrollment. Of 915 women, non-retention was observed for 18%. Prevalence of syndemic factors was adolescent pregnancy (53.2%), physical/sexual violence (38.3%), induced abortion (27.3%), and illicit drug use (17.2%); 41.2% experienced ≥ 2 syndemic conditions. Syndemic scores of 2 and 3 were associated with non-retention, as well as low education, years with HIV and seroprevalent syphilis. Psychosocial and reproductive syndemics can limit women's retention in HIV care. Syphilis infection predicted non-retention and could be explored as a syndemic factor in future studies.

PrEP policy implementation gaps and opportunities in Latin America and the Caribbean: a scoping review.

Background: Pre-exposure prophylaxis (PrEP) is an important tool for HIV prevention in Latin America and the Caribbean (LAC). Yet, little is known about the PrEP policies landscape in the region. Addressing this gap, this scoping review assessed current PrEP policies throughout LAC to better understand existing PrEP implementation gaps and identify opportunities to improve access. Methods: We conducted a scoping review, using a modified PRISMA extension, through 28 July 2022, to identify country-level PrEP policies. Data were collected in English, Spanish, French, and Portuguese utilizing online platforms for screening and data extraction (Google Forms, Zotero, and Excel). Extracted data were divided by data source, including country-level government policies, gray literature, and peer-reviewed literature, with at least one full-text reviewer and data extractor per publication. An iterative summative content analysis was performed to compare and interpret themes across phases and data sources. Results: Of the 33 countries in LAC, 22 (67%) had policies approving daily oral PrEP for HIV prevention, which outlined specific key populations, including men who have sex with men, transgender women, sex workers, and serodiscordant couples. Generic tenofovir disoproxil fumarate/emtricitabine has been approved in 15 of the 33 countries, and 13 of the 33 countries have incorporated PrEP into their public health system. No countries were found to have approved cabotegravir. Costing data were reported by only one country, Ecuador, in its national health ministry guidelines. Findings also document a lag between the media/gray-literature announcement of PrEP and implementation of policies. Conclusion: Findings underscore significant advances in PrEP policies in the region and signal opportunities for greater PrEP implementation. Since 2017, an increasing number of countries have begun to provide PrEP to communities at heightened need, although significant gaps remain. Policy approval is a key step to further increasing access to PrEP in LAC, necessary to reduce the burden of HIV in LAC, specifically among marginalized populations.

The Impact of COVID-19 on HIV Care in Rio de Janeiro, Brazil 2019-2021: Disparities by Age and Gender.

We evaluated COVID-19's impact on HIV care indicators among INI/FIOCRUZ's HIV Clinical Cohort in Rio de Janeiro, Brazil: (1) Adequate care visits: two visits ≥ 90 days apart; (2) Adequate viral load monitoring: ≥ 2 viral load results ≥ 90 days apart; (3) Consistent viral suppression: all viral loads < 40 copies/mL; and (4) ART medication possession ratio (MPR) ≥ 95%. Chi-square tests compared the fraction of participants meeting each indicator per period: pre-pandemic (3/1/2019-2/29/2020) and post-pandemic (3/1/2020-2/28/2021). Logistic regression models were used to assess disparities in adequate care visits. Among 906 participants, care visits and viral load monitoring decreased pre-pandemic to post-pandemic: 77.0-55.1% and 36.6-11.6% (both p < 0.001), respectively. The optimal MPR rate improved from 25.5 to 40.0% (p < 0.001). Post-pandemic period (aOR 0.33, CI 0.28-0.40), transgender women (aOR 0.34, CI 0.22-0.53), and those aged 18-24 years (aOR 0.67, CI 0.45-0.97) had lower odds of adequate care visits. COVID-19 disrupted care access disproportionately for transgender women and younger participants.

Brief Report: Impact of Methamphetamine Use and Rectal STIs on Systemic and Rectal Mucosal Inflammation.

BACKGROUND: Methamphetamine (MA) use is associated with sexual risk behavior as well as systemic and mucosal inflammation, suggesting parallel biological and behavioral mechanisms of HIV transmission among men who have sex with men (MSM) who use MA. Data evaluating the combined biological effects of MA use with concomitant rectal gonococcal and/or chlamydial (GC/CT) infection on inflammation are limited. SETTING: Secondary analysis of stored rectal and plasma specimens from 100 MSM participating in an NIDA-funded longitudinal cohort in Los Angeles, CA. METHODS: This cross-sectional analysis evaluated systemic and rectal inflammatory markers under 2 conditions: (1) recent MA use (by urine drug screen) and (2) rectal GC/CT infection. We evaluated 50 participants with recent MA use (25 with and 25 without rectal GC/CT) and 50 MSM without MA use (25 with and 25 without rectal GC/CT). Log-transformed plasma and rectal immune markers were regressed on MA exposure and rectal GC/CT, controlling for HIV status and age. RESULTS: Median age was 32 (range 19-45) years, and 58% of participants were living with HIV. Plasma tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-8, IL-1ß, and rectal IL-6 were associated with rectal GC/CT and MA use, independent of HIV status. Higher levels of rectal TNF-α, IL-1ß, and IL-17a were associated with rectal GC/CT. CONCLUSIONS: Systemic and rectal inflammation was positively associated with rectal GC/CT and MA use. Condomless sex in the setting of GC/CT- and MA-induced immune activation may provide a basis for synergistic biobehavioral mechanisms that promote HIV/STI transmission among MSM who use MA.

Contingency Management for Integrated Harm Reduction Among Men Who Have Sex with Men Who Use Methamphetamine in Los Angeles: A Pilot Assessment.

Methamphetamine (MA) use is associated with HIV transmission among men who have sex with men (MSM) and lapses in medication adherence. Contingency Management (CM) is effective in reducing MA use, but studies of CM to support adherence to HIV prevention or treatment are limited. We conducted a pilot trial of a CM intervention to reduce MA use and improve PrEP/ART adherence among MSM prescribed a tenofovir (TFV)-based regimen for HIV prevention or treatment. Participants were randomly assigned to receive escalating incentives for either MA abstinence or TFV adherence (based on point-of-care urine testing), and to a monitoring schedule of either 2 or 3 visits/week for 4 weeks. 19 MSM were randomized to either CM for MA use or CM for PrEP/ART adherence (median age: 38; IQR: 28-46) and 15 were living with HIV. Participants attended 95.7% (67/70) of scheduled visits in the 2x/week arm and 74.8% (74/99) in the 3x/week arm. TFV adherence was higher among participants in the TFV adherence arm with 93.5% (n = 72/77) of urine samples positive for TFV, compared to 76.6% (n = 49/64) in the MA abstinence arm (p = 0.007). Participants in the MA abstinence arm had more urine samples negative for MA metabolites (20.3%, n = 13/64) than those receiving CM for TFV adherence (6.5%, n = 5/77; p = 0.021). A CM model for MA abstinence and PrEP/ART adherence using twice-weekly visits and urine testing for MA and TFV for MSM who use MA is feasible and potentially effective as an integrated harm reduction strategy.

Reproductive health syndemics impact retention in care among women living with HIV in Rio de Janeiro, Brazil

ABSTRACT Syndemic psychosocial and reproductive factors affecting women's retention in HIV care remain understudied. We analyzed correlates of non-retention in a cohort of women with HIV in Brazil from 2000-2015. Participants self-reported exposure to physical/sexual violence, illicit drug use, adolescent pregnancy, or induced abortion. Lifetime history of these psychosocial stressors were used to create a syndemic score based on the presence or absence of these conditions. All dichotomous variables were summed (range 0 to 4), with greater scores indicating more syndemic factors experienced. Logistic regression models identified predictors of non-retention, defined as < 2 HIV viral load or CD4 results within the first year of enrollment. Of 915 women, non-retention was observed for 18%. Prevalence of syndemic factors was adolescent pregnancy (53.2%), physical/sexual violence (38.3%), induced abortion (27.3%), and illicit drug use (17.2%); 41.2% experienced > 2 syndemic conditions. Syndemic scores of 2 and 3 were associated with non-retention, as well as low education, years with HIV and seroprevalent syphilis. Psychosocial and reproductive syndemics can limit women's retention in HIV care. Syphilis infection predicted non-retention and could be explored as a syndemic factor in future studies.

Critical Consciousness for Connectivity: Decoding Social Isolation Experienced by Latinx and LGBTQ+ Youth Using a Multi-Stakeholder Approach to Health Equity.

Systemic oppression creates a context in which Latinx LGBTQ+ youth experience social isolation. Social isolation has been associated with mental and physical health disparities, including disproportionate levels of depression, substance use, self-harm, and attempted suicide. These disparities are often magnified in rural and suburban areas with fewer identity-affirming spaces. This community-engaged study reports on the formative process of developing a Latinx LGBTQ+ telenovela (soap opera) allyship intervention based on critical consciousness theory. We conducted eight focus groups with community advisory boards, which included Latinx LGBTQ+ youth (n = 12), health and social service providers serving LGBTQ+ youth (n = 10), 4-H Latinx alumni youth (n = 12), and 4-H Latinx parents (n = 8). We interviewed nine Latinx LGBTQ+ youth enrolled in a film-making workshop. As a result of our multi-stakeholder approach, we: (1) described how stakeholders reflected on and decoded intersectional isolation on the individual, community, and structural levels; and (2) identified ways that stakeholders suggested taking action by improving access to resources to address social isolation, provide culturally competent healthcare, and co-create an enabling social environment. Our study indicated the importance of tapping into core values and intersectional identities to build solidarity among and within marginalized groups to dismantle oppressive systems.

Gut dysbiosis and inflammatory blood markers precede HIV with limited changes after early seroconversion.

BACKGROUND: Alterations in the gut microbiome have been associated with HIV infection, but the relative impact of HIV versus other factors on the gut microbiome has been difficult to determine in cross-sectional studies. METHODS: To address this, we examined the gut microbiome, serum metabolome, and cytokines longitudinally within 27 individuals before and during acute HIV using samples collected from several ongoing cohort studies. Matched control participants (n=28) from the same cohort studies without HIV but at similar behavioral risk were used for comparison. FINDINGS: We identified few changes in the microbiome during acute HIV infection, but did find alterations in serum metabolites involving secondary bile acid (lithocholate sulfate, glycocholenate sulfate) and amino acid metabolism (3-methyl-2-oxovalerate, serine, cysteine, N-acetylputrescine). Greater microbiome differences, including decreased Bacteroides spp and increased Megasphaera elsdenii, were seen when comparing pre-HIV infection visits to matched at-risk controls. Those who acquired HIV also had elevated inflammatory cytokines (TNF-α, B cell activating factor, IL-8) and bioactive lipids (palmitoyl-sphingosine-phosphoethanolamide and glycerophosphoinositol) prior to HIV acquisition compared to matched controls. INTERPRETATION: Longitudinal sampling identified pre-existing microbiome differences in participants with acute HIV compared to matched control participants observed over the same period. These data highlight the importance of increasing understanding of the role of the microbiome in HIV susceptibility. FUNDING: This work was supported by NIH/NIAID (K08AI124979; P30AI117943), NIH/NIDA (U01DA036267; U01DA036939; U01DA036926; U24DA044554), and NIH/NIMH (P30MH058107; R34MH105272).

Baricitinib versus dexamethasone for adults hospitalised with COVID-19 (ACTT-4): a randomised, double-blind, double placebo-controlled trial.

BACKGROUND: Baricitinib and dexamethasone have randomised trials supporting their use for the treatment of patients with COVID-19. We assessed the combination of baricitinib plus remdesivir versus dexamethasone plus remdesivir in preventing progression to mechanical ventilation or death in hospitalised patients with COVID-19. METHODS: In this randomised, double-blind, double placebo-controlled trial, patients were enrolled at 67 trial sites in the USA (60 sites), South Korea (two sites), Mexico (two sites), Singapore (two sites), and Japan (one site). Hospitalised adults (≥18 years) with COVID-19 who required supplemental oxygen administered by low-flow (≤15 L/min), high-flow (>15 L/min), or non-invasive mechanical ventilation modalities who met the study eligibility criteria (male or non-pregnant female adults ≥18 years old with laboratory-confirmed SARS-CoV-2 infection) were enrolled in the study. Patients were randomly assigned (1:1) to receive either baricitinib, remdesivir, and placebo, or dexamethasone, remdesivir, and placebo using a permuted block design. Randomisation was stratified by study site and baseline ordinal score at enrolment. All patients received remdesivir (≤10 days) and either baricitinib (or matching oral placebo) for a maximum of 14 days or dexamethasone (or matching intravenous placebo) for a maximum of 10 days. The primary outcome was the difference in mechanical ventilation-free survival by day 29 between the two treatment groups in the modified intention-to-treat population. Safety analyses were done in the as-treated population, comprising all participants who received one dose of the study drug. The trial is registered with ClinicalTrials.gov, NCT04640168. FINDINGS: Between Dec 1, 2020, and April 13, 2021, 1047 patients were assessed for eligibility. 1010 patients were enrolled and randomly assigned, 516 (51%) to baricitinib plus remdesivir plus placebo and 494 (49%) to dexamethasone plus remdesivir plus placebo. The mean age of the patients was 58·3 years (SD 14·0) and 590 (58%) of 1010 patients were male. 588 (58%) of 1010 patients were White, 188 (19%) were Black, 70 (7%) were Asian, and 18 (2%) were American Indian or Alaska Native. 347 (34%) of 1010 patients were Hispanic or Latino. Mechanical ventilation-free survival by day 29 was similar between the study groups (Kaplan-Meier estimates of 87·0% [95% CI 83·7 to 89·6] in the baricitinib plus remdesivir plus placebo group and 87·6% [84·2 to 90·3] in the dexamethasone plus remdesivir plus placebo group; risk difference 0·6 [95% CI -3·6 to 4·8]; p=0·91). The odds ratio for improved status in the dexamethasone plus remdesivir plus placebo group compared with the baricitinib plus remdesivir plus placebo group was 1·01 (95% CI 0·80 to 1·27). At least one adverse event occurred in 149 (30%) of 503 patients in the baricitinib plus remdesivir plus placebo group and 179 (37%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 7·5% [1·6 to 13·3]; p=0·014). 21 (4%) of 503 patients in the baricitinib plus remdesivir plus placebo group had at least one treatment-related adverse event versus 49 (10%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 6·0% [2·8 to 9·3]; p=0·00041). Severe or life-threatening grade 3 or 4 adverse events occurred in 143 (28%) of 503 patients in the baricitinib plus remdesivir plus placebo group and 174 (36%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 7·7% [1·8 to 13·4]; p=0·012). INTERPRETATION: In hospitalised patients with COVID-19 requiring supplemental oxygen by low-flow, high-flow, or non-invasive ventilation, baricitinib plus remdesivir and dexamethasone plus remdesivir resulted in similar mechanical ventilation-free survival by day 29, but dexamethasone was associated with significantly more adverse events, treatment-related adverse events, and severe or life-threatening adverse events. A more individually tailored choice of immunomodulation now appears possible, where side-effect profile, ease of administration, cost, and patient comorbidities can all be considered. FUNDING: National Institute of Allergy and Infectious Diseases.

Exploring Contextual Differences for Sexual Role Strain Among Transgender Women and Men Who Have Sex with Men in Lima, Peru.

Sexual and gender politics inform relational expectations surrounding sexual experiences of Peruvian transgender women (TW) and men who have sex with men (MSM). We used the framework of sexual role strain, or incongruence between preferred sexual role and actual sexual practices, to explore potential conflicts between personally articulated identities and externally defined norms of gender and sexuality and its potential to increase HIV/STI risk. Cross-sectional individual- and dyad-level data from 766 TW and MSM in Lima, Peru were used to assess the partnership contexts within which insertive anal intercourse was practiced despite receptive role preference (receptive role strain), and receptive anal intercourse practiced despite insertive role preference (insertive role strain). Sexual role strain for TW was more common with non-primary partners, while for MSM it occurred more frequently in the context of a primary partnership. Receptive role strain was more prevalent for TW with unknown HIV status (reference: without HIV) or pre-sex drug use (reference: no pre-sex drug use). For homosexual MSM, receptive role strain was more prevalent during condomless anal intercourse (reference: condom-protected) and with receptive or versatile partners (reference: insertive). Among heterosexual or bisexual MSM, insertive role strain was more prevalent with insertive or versatile partners (reference: receptive), and less prevalent with casual partners (reference: primary). Our findings suggest TW and MSM experience different vulnerabilities during sexual role negotiation with different partner-types. Future studies should explore the impact of sexual role strain on condom use agency, HIV/STI risk, and discordances between public and private presentations of gender and sexual orientation.

Decision-Making at the Intersection of Risk and Pleasure: A Qualitative Inquiry with Trans Women Engaged in Sex Work in Lima, Peru.

To inform culturally relevant HIV prevention interventions, we explore the complexity of sex work among Peruvian transgender women. In 2015, we conducted twenty in-depth interviews and demographic surveys with transgender women in Lima, Peru to examine how transgender women enact individual- and community-level resistance strategies within a context of pervasive marginalization. Although 40% self-identified as "sex workers," 70% recently exchanged sex for money. Participants described nuanced risk-benefit analyses surrounding paid sexual encounters. Classification of clients as "risky" or "rewarding" incorporated issues of health, violence, and pleasure. Interviews highlighted context-informed decision-making (rejecting disrespectful clients, asserting condom use with specific partner types) demonstrating that motivations were not limited to HIV prevention or economic renumeration, but considered safety, health, attraction, gender validation, hygiene, and convenience. These findings underscore the complex risk assessments employed by Peruvian trans women. These individual-level decision-making and context-specific health promotion strategies represent critical frameworks for HIV prevention efforts.

The wisdom of mistrust: qualitative insights from transgender women who participated in PrEP research in Lima, Peru.

INTRODUCTION: Although pre-exposure prophylaxis (PrEP) is a remarkable biomedical advance to prevent HIV, ongoing research on PrEP contributes to and interacts with a legacy of HIV experimentation on marginalized communities in resource-limited settings. This paper explores the complexity of PrEP research mistrust among Peruvian transgender (trans) women who completed a PrEP adherence intervention and those who refused participation (i.e. declined to enrol, voluntarily withdrew, and/or were lost to follow-up). METHODS: Data were derived from 86 trans women (mean age 29 years) participants in the formative (four focus groups (n = 32), 20 interviews) and the evaluation stages (34 interviews) of a social network-based PrEP intervention for trans women in Lima, Peru. The formative stage took place from May to July 2015, while the evaluative stage took place from April to May 2018. Audio files were transcribed verbatim and analysed via an immersion crystallization approach using Dedoose (v.6.1.18). RESULTS: Three paradoxes of trans women's participation in PrEP science as a "key" population emerged as amplifying mistrust: (1) increases in PrEP research targeting trans women but limited perceived improvements in HIV outcomes; (2) routine dismissal by research physicians and staff of PrEP-related side effects and the social realities of taking PrEP, resulting in questions about who PrEP research is really for and (3) persistent limitations on PrEP access for trans women despite increasing involvement in clinical trials, fostering feelings of being a "guinea pig" to advance PrEP science. CONCLUSIONS: Findings highlight the wisdom inherent in PrEP mistrust as a reflection of trans women's experiences that underscore the broken bonds of trust between communities, researchers and the research enterprise. PrEP mistrust is amplified through perceived paradoxes that suggest to trans women that they are key experimental participants but not target PrEP users outside of research settings. Findings highlight the urgent need to reframe mistrust not as a characteristic of trans women to be addressed through education and outreach, but as a systemic institutional- and industry-level problem replicated, manifested and ultimately to be corrected, through global HIV science.

Pre-exposure prophylaxis awareness, use, and intention to use in a regional sample of Latin American geosocial networking application users in 2018-2019.

Pre-exposure prophylaxis (PrEP) access is increasing in Latin America. We explored PrEP use among Spanish-speaking, Hornet geosocial networking application users from Latin American countries with limited PrEP data via an online survey completed between December 2018 and February 2019. A total of 718 Hornet users from 10 countries were included, of whom 72.1% reported PrEP awareness. Few (5.6%) were currently taking PrEP, though 32.1% intended to take PrEP in the subsequent 6 months. PrEP awareness was lower in 18-25 year olds compared to 26+ (62.4% vs. 75.6%, aOR 0.67, [95% CI 0.46-0.97]), and higher among those living in larger versus smaller cities (74.4% vs. 58.8%, aOR 1.96, [95% CI 1.25-3.07]) or countries with at least partial versus no PrEP policy adoption (79.1% vs. 60.8%, aOR 2.20, [95% CI 1.56-3.12]). Intention to use PrEP was higher among PrEP-eligible respondents (51.8% vs. 29.6%, aOR 2.26, [95% CI 1.26-4.07]) and those recently tested for a sexually transmitted infection (35.4% vs. 25.5%, aOR 1.58, [95% CI 1.01-2.48]). Efforts to expand PrEP use in Latin America should focus on national PrEP policy adoption, and research should explore barriers to awareness and use among young men who have sex with men.

Sexual health norms and communication patterns within the close social networks of men who have sex with men and transgender women in Lima, Peru: a 2017 cross-sectional study.

BACKGROUND: Social networks, norms, and discussions about sexual health may inform sexual practices, influencing risk of human immunodeficiency virus (HIV) or sexually transmitted infection (STI) acquisition. To better understand social networks of Peruvian men who have sex with men (MSM) and transgender women (trans women), we examined key social network members (SNMs), participant perceptions of these network members' opinions toward sexual health behaviors, and associations between network member characteristics and condomless anal intercourse (CAI). METHODS: In a 2017 cross-sectional study, a convenience sample of 565 MSM and trans women with HIV-negative or unknown serostatus was asked to identify three close SNMs; describe discussions about HIV and STI prevention with each; and report perceived opinions of condom use, HIV/STI testing, and partner notification of STIs. Generalized estimating equations evaluated relationships between SNM characteristics, opinions, and discussions and participant-reported CAI. RESULTS: Among participants who identified as MSM, 42.3% of key SNMs were perceived to identify as gay. MSM "never" discussed HIV and STI prevention concerns with 42.4% of heterosexual SNMs, but discussed them "at least once weekly" with 16.9 and 16.6% of gay- and bisexual- identifying SNMs, respectively. Among participants who identified as trans women, 28.2% of key SNMs were perceived as heterosexual; 25.9%, as bisexual; 24.7%, as transgender; and 21.2%, as gay. Trans women discussed HIV/STI prevention least with cis-gender heterosexual network members (40.2% "never") and most with transgender network members (27.1% "at least once weekly"). Participants perceived most of their close social network to be completely in favor of condom use (71.2% MSM SNMs, 61.5% trans women SNMs) and HIV/STI testing (73.1% MSM SNMs, 75.6% trans women SNMs), but described less support for partner STI notification (33.4% MSM SNMs, 37.4% trans women SNMs). Most participants reported CAI with at least one of their past three sexual partners (77.5% MSM, 62.8% trans women). SNM characteristics were not significantly associated with participant-reported frequency of CAI. CONCLUSIONS: Findings compare social support, perceived social norms, and discussion patterns of Peruvian MSM and trans women, offering insight into social contexts and sexual behaviors. TRIAL REGISTRATION: The parent study from which this analysis was derived was registered at ClinicalTrials.gov (Identifier: NCT03010020 ) on January 4, 2017.