Abstract Background In Lima, Peru, the HIV epidemic is concentrated among men who have sex with men (MSM) and transgender women (TW). Few data exist on the sexual network characteristics of MSM with detectable HIV-1 viremia, yet these networks have important implications to control transmission. We report data on frequency of sero-discordant, condomless anal intercourse (CAI) among MSM in Lima with detectable viremia. Methods This cross-sectional secondary analysis includes MSM screened for a STI trial in Lima, Peru between June 2022 and January 2023. Participants completed questionnaires on demographics, sexual identity and role, and sexual network characteristics. Participants were screened for HIV infection and those who tested positive were included and HIV-1 RNA was measured. Descriptive and comparative statistics are reported for those with detectable and undetectable viremia. Results 665 MSM with HIV were included. 153 (23%) had detectable ( >200 copies/mL) viremia. Among those with detectable viremia, the median (IQR) age was 29 (25, 35) years. 70% identified as homosexual and 57% identified their sexual role during intercourse as “moderno” or “versatil”. The median (IQR) number of sexual partners in the last 3 months was 15 (5,20). 55/153 (35.6%) of the detectable group were aware of their HIV diagnosis, 33/55 (60%) reported being on anti-retroviral therapy (ART) and 15/32 (47%) believed they were virally suppressed. Among all participants living with HIV, 499/662 (75%) were aware of their HIV status, 469/499 (94%) reported to be on ART and 436/469 (93%) were virally suppressed. 147/153 (96%) of men with detectable viremia reported sero-discordant CAI with at least one of their last three sexual partners, and 106/144 (74%) reported this with all three of their last partners. In the undetectable group, 302/489 (62%) reported sero-discordant CAI with all three of their last partners (p < 0.01). Conclusion In this sample of MSM living with HIV in Lima, Peru, almost all men with detectable HIV-1 viremia reported sero-discordant CAI, more often than those with undetectable viremia. The primary gap in the HIV care cascade was participant awareness of their HIV status, suggesting that broader HIV testing and improved access to resources for secondary HIV prevention are key objectives in Peru. Disclosures Jordan Lake, MD, Gilead Sciences: Grant/Research Support|Theratechnologies: Advisor/Consultant

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. 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-1β, 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. 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). 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.

The phase 2b proof-of-concept Antibody Mediated Prevention (AMP) trials showed that VRC01, an anti-HIV-1 broadly neutralising antibody (bnAb), prevented acquisition of HIV-1 sensitive to VRC01. To inform future study design and dosing regimen selection of candidate bnAbs, we investigated the association of VRC01 serum concentration with HIV-1 acquisition using AMP trial data. The case-control sample included 107 VRC01 recipients who acquired HIV-1 and 82 VRC01 recipients who remained without HIV-1 during the study. We measured VRC01 serum concentrations with a qualified pharmacokinetic (PK) Binding Antibody Multiplex Assay. We employed nonlinear mixed effects PK modelling to estimate daily-grid VRC01 concentrations. Cox regression models were used to assess the association of VRC01 concentration at exposure and baseline body weight, with the hazard of HIV-1 acquisition and prevention efficacy as a function of VRC01 concentration. We also compared fixed dosing vs. body weight-based dosing via simulations. Estimated VRC01 concentrations in VRC01 recipients without HIV-1 were higher than those in VRC01 recipients who acquired HIV-1. Body weight was inversely associated with HIV-1 acquisition among both placebo and VRC01 recipients but did not modify the prevention efficacy of VRC01. VRC01 concentration was inversely correlated with HIV-1 acquisition, and positively correlated with prevention efficacy of VRC01. Simulation studies suggest that fixed dosing may be comparable to weight-based dosing in overall predicted prevention efficacy. These findings suggest that bnAb serum concentration may be a useful marker for dosing regimen selection, and operationally efficient fixed dosing regimens could be considered for future trials of HIV-1 bnAbs. Was provided by the National Institutes of Health, National Institute of Allergy and Infectious Diseases (NIAID) (UM1 AI068614, to the HIV Vaccine Trials Network [HVTN]; UM1 AI068635, to the HVTN Statistical Data and Management Center [SDMC], Fred Hutchinson Cancer Center [FHCC]; 2R37 054165 to the FHCC; UM1 AI068618, to HVTN Laboratory Center, FHCC; UM1 AI068619, to the HPTN Leadership and Operations Center; UM1 AI068613, to the HIV Prevention Trials Network [HPTN] Laboratory Center; UM1 AI068617, to the HPTN SDMC; and P30 AI027757, to the Center for AIDS Research, Duke University (AI P30 AI064518) and University of Washington (P30 AI027757) Centers for AIDS Research; R37AI054165 from NIAID to the FHCC; and OPP1032144 CA-VIMC Bill & Melinda Gates Foundation.

To describe the prevalence of acute retroviral syndrome (ARS) and associated findings during primary HIV, and explore the relationship of ARS to clinical, virological, and immunological outcomes within a longitudinal screen, retest and treat study that minimized ascertainment bias. We evaluated ARS symptoms and signs among 216 persons with acute and early incident HIV within the Sabes study of timing of antiretroviral therapy (ART) initiation during primary HIV in Peru. We evaluated patient reported symptoms and signs during primary HIV and used logistic regression and generalized linear models to evaluate associations with CD4 + and CD8 + T cell counts, HIV viral load, and a panel of 23 soluble markers of immune activation. Sixty-one percent of participants had at least one ARS finding and 35% had at least 3. More ARS findings were reported in those enrolled within a month of estimated date of detectable infection (EDDI). Having more ARS signs/symptoms was associated with increased risk of CD4 + cell decrease below 350 cells/ml within the first 24 weeks, failure to suppress HIV viral load, and was most strongly associated with elevated IP-10. Immediate ART blunted effects on symptoms, CD4 + cell count and viral load, as associations were strongest in the arm that started ART after 24 weeks. Detrimental associations of ARS with CD4 + counts, and CD4 + /CD8 + ratio were not maintained at 2 or 4 years. ARS has marked associations with short-term immunologic function and virologic suppression, which were mitigated in participants randomized to initiate ART immediately during primary infection.

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. 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. 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. 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 HPTN 083 trial demonstrated that long-acting cabotegravir (CAB-LA) was superior to tenofovir-disoproxil fumarate/emtricitabine for human immunodeficiency virus (HIV) preexposure prophylaxis (PrEP). Integrase strand transfer inhibitor (INSTI) resistance-associated mutations (RAMs) were detected in some participants with HIV infection. We used a low viral load INSTI genotyping assay to evaluate the timing of emergence of INSTI RAMs and assessed whether HIV screening with a sensitive RNA assay would have detected HIV infection before INSTI resistance emerged. Single-genome sequencing to detect INSTI RAMs was performed for samples with viral loads <500 copies/mL from 5 participants with previously identified INSTI RAMs and 2 with no prior genotyping results. Major INSTI RAMs were detected in all 7 cases. HIV RNA testing identified infection before major INSTI RAMs emerged in 4 cases and before additional major INSTI RAMs accumulated in 1 case. Most INSTI RAMs were detected early when the viral load was low and CAB concentration was high. When using CAB-LA PrEP, earlier detection of HIV infection with a sensitive RNA assay may allow for earlier treatment initiation with the potential to reduce INSTI resistance risk. Further studies are needed to evaluate the value and feasibility of HIV RNA testing with CAB-LA PrEP.

The quadrivalent human papillomavirus (HPV) vaccine was shown to prevent infections and lesions related to HPV6, 11, 16, and 18 in a randomised, placebo-controlled study in men aged 16-26 years. We assessed the incidences of external genital warts related to HPV6 or 11, and external genital lesions and anal dysplasia related to HPV6, 11, 16, or 18, over 10 years of follow-up. The 3-year base study was an international, multicentre, double-blind, randomised, placebo-controlled trial done at 71 sites in 18 countries. Eligible participants were heterosexual men (aged 16-23 years) or men who have sex with men (MSM; aged 16-26 years). Men who had clinically detectable anogenital warts or genital lesions at screening that were suggestive of infection with non-HPV sexually transmitted diseases, or who had a history of such findings, were excluded. Eligible participants were randomly assigned (1:1) to receive three doses of either quadrivalent HPV vaccine or placebo on day 1, month 2, and month 6, administered as a 0·5-mL injection into the deltoid muscle. The 7-year, open-label, long-term follow-up extension study was done at 46 centres in 16 countries. Participants who received one or more doses of the quadrivalent HPV vaccine in the base study were eligible for enrolment into the long-term follow-up study (early vaccination group). Placebo recipients were offered the three-dose quadrivalent HPV vaccine at the end of the base study; those who received one or more quadrivalent HPV vaccine doses were eligible for enrolment into the long-term follow-up study (catch-up vaccination group). The primary efficacy endpoints were the incidence of external genital warts related to HPV6 or 11 and the incidence of external genital lesions related to HPV6, 11, 16, or 18 in all participants and the incidence of anal intraepithelial neoplasia (including anal warts and flat lesions) or anal cancer related to HPV6, 11, 16, or 18 in MSM only. The primary efficacy analysis was done in the per-protocol population for the early vaccination group, which included participants who received all three vaccine doses, were seronegative at day 1 and PCR-negative from day 1 through month 7 of the base study for the HPV type being analysed, had no protocol violations that could affect evaluation of vaccine efficacy, and had attended at least one visit during the long-term follow-up study. For the catch-up vaccination group, efficacy was assessed in the modified intention-to-treat population, which included participants who had received at least one vaccine dose, were seronegative and PCR-negative for HPV types analysed from day 1 of the base study to the final follow-up visit before receiving the quadrivalent HPV vaccine, and had at least one long-term follow-up visit. Safety was assessed in all randomised participants who received at least one vaccine dose. This study is registered with ClinicalTrials.gov, NCT00090285. Between Aug 10, 2010, and April 3, 2017, 1803 participants were enrolled in the long-term follow-up study, of whom 936 (827 heterosexual men and 109 MSM) were included in the early vaccination group and 867 (739 heterosexual men and 128 MSM) were included in the catch-up vaccination group. Participants in the early vaccination group were followed up for a median of 9·5 years (range 0·1-11·5) after receiving the third dose of the quadrivalent HPV vaccine, and participants in the catch-up vaccination group were followed up for a median of 4·7 years (0·0-6·6) after receiving the third dose. In early vaccine group participants during long-term follow-up compared with the placebo group in the base study, the incidence per 10 000 person-years of external genital warts related to HPV6 or 11 was 0·0 (95% CI 0·0-8·7) versus 137·3 (83·9-212·1), of external genital lesions related to HPV6, 11, 16, or 18 was 0·0 (0·0-7·7) versus 140·4 (89·0-210·7), and of anal intraepithelial neoplasia or anal cancer related to HPV6, 11, 16, or 18 in MSM only was 20·5 (0·5-114·4) versus 906·2 (553·5-1399·5). Compared with during the base study (ie, before quadrivalent HPV vaccine administration), during the long-term follow-up period, participants in the catch-up vaccination group had no new reported cases of external genital warts related to HPV6 or 11 (149·6 cases per 10 000 person-years [95% CI 101·6-212·3] vs 0 cases per 10 000 person-years [0·0-13·5]) or external genital lesions related to HPV6, 11, 16, or 18 (155·1 cases per 10 000 person-years [108·0-215·7] vs 0 cases per 10 000 person-years [0·0-10·2]), and a lower incidence of anal intraepithelial neoplasia or anal cancer related to HPV6, 11, 16, or 18 (886·0 cases per 10 000 person-years [583·9-1289·1] vs 101·3 cases per 10 000 person-years [32·9-236·3]). No vaccine-related serious adverse events were reported. The quadrivalent HPV vaccine provides durable protection against anogenital disease related to HPV6, 11, 16, and 18. The results support quadrivalent HPV vaccination in men, including catch-up vaccination. Merck Sharp & Dohme.

ABSTRACT In Lima, Peru, men who have sex with men (MSM) and transgender women (TW) are disproportionately affected by HIV. Patterns of sexual behavior vary by sexual partner type, which has implications for HIV prevention intervention design. We examine correlates of sex and condomless anal intercourse (CAI) with each of four types of partners among HIV-negative MSM and TW in Lima who completed monthly questionnaires about partnership types and CAI. Odds ratios were calculated using generalized estimating equations to identify correlates of being in different types of partnerships and CAI within those partnerships. Among 1,831 MSM and TW with over 14,792 study visits, CAI was most reported with main partners, followed by casual partners, one-time partners, and clients. Presence of an alcohol use disorder (AUD) significantly increased the odds of CAI with all types of partners (main: OR 1.36 (95% CI 1.17-1.57); casual: 1.49 (1.27-1.75); one-time: 1.45 (1.22-1.72); client 1.52 (1.12-2.08)); recent alcohol use increased odds of CAI with main partners. Having one main partner decreased the odds of being in casual and one-time partnerships and of CAI in all types of partnerships. Interventions targeting AUDs and individuals with multiple sexual contacts could reduce CAI and HIV risk in this population. Clinical trial registration The Sabes study was registered in March 2013 with the National Institutes of Health at ClinicalTrials.gov (identifier: NCT01815580).

BackgroundSocial 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).MethodsIn 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.ResultsAmong 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.ConclusionsFindings compare social support, perceived social norms, and discussion patterns of Peruvian MSM and trans women, offering insight into social contexts and sexual behaviors.Trial registrationThe parent study from which this analysis was derived was registered at ClinicalTrials.gov (Identifier: NCT03010020) on January 4, 2017.

Determine the impact of HIV-1 seroconversion on inflammatory cytokines in the rectal mucosa. Secondary analysis of data from men who have sex with men and transgender women who participated in a HIV prevention trial Lima, Peru. From July to December 2017, 605 men who have sex with men and transgender women were screened for rectal gonorrhea/chlamydia (GC/CT). Fifty GC/CT-positive cases were randomly selected and matched with 52 GC/CT-negative controls by age and number of receptive anal intercourse partners in the last month. All participants were HIV-negative at baseline and those with GC/CT at baseline and/or follow-up received appropriate antibiotic therapy. Participants underwent sponge collection of rectal secretions for the measurement of inflammatory cytokines (IL-1β, IL-6, IL-8, and TNF-α) and were screened for rectal GC/CT and HIV at baseline, 3 months, and 6 months. Wilcoxon rank-sum tests compared inflammatory cytokine levels between participants diagnosed with HIV during follow-up and persons who remained HIV-negative. Eight participants were diagnosed with HIV at the 3-month (n = 6) or 6-month (n = 2) visit. The median number of receptive anal intercourse partners in the month before HIV diagnosis was the same for those who acquired HIV and those who did not. There were no significant differences in inflammatory cytokine levels in rectal mucosa between participants who did and did not experience HIV seroconversion at any time point. Despite a surge in viral replication during acute infection, findings from this study suggest that there is no prolonged effect of HIV-1 seroconversion on inflammatory cytokine levels in the rectal mucosa.