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INTRODUCTION: HPTN 083 demonstrated the superiority of long-acting cabotegravir (CAB-LA) versus daily oral emtricitabine/tenofovir disoproxil fumarate (TDF/FTC) as pre-exposure prophylaxis (PrEP) among cisgender men and transgender women who have sex with men (MSM/TGW). HPTN 083 provided the first opportunity to understand experiences with injectable PrEP in a clinical trial. METHODS: Participants from two US sites (Chicago, IL and Atlanta, GA) and one international site (Rio de Janeiro, Brazil) were purposively sampled for individual qualitative interviews (N = 40), between November 2019 and March 2020, to explore trial experiences, barriers to adherence and other factors that may have impacted study implementation or outcomes. The blinded phase ended early due to efficacy; this analysis includes interviews conducted prior to unblinding with three groups defined by adherence (i.e. injection visit attendance): adherent (n = 27), non-adherent (n = 12) and early discontinuers (n = 1). Data were organized using NVivo software and analysed using content analysis. RESULTS: Participants (mean age: 27) were primarily cisgender MSM (90%) and Black/African American (60%). Reasons for trial enrolment and PrEP use included a preference for using HIV prevention medication versus treatment in the event of HIV acquisition; the ability to enhance health via study-related education and services; access to a novel, convenient HIV prevention product at no cost; and contributing to MSM/TGW communities through research. Participants contrasted positive experiences with study staff with their routine clinical care, and emphasized increased scheduling flexibility, thorough communication, non-judgemental counselling and open, affirming environments (e.g. compassion, less stigma) as adherence facilitators. Injection experiences were positive overall; some described early injection-related anxiety, which abated with time and when given some measure of control (e.g. pre-injection countdown), and minimal injection site discomfort. Some concerns and misperceptions about injectable PrEP were reported. Barriers to adherence, across all adherence categories, included structural factors (e.g. financial constraints, travel) and competing demands (e.g. work schedules). CONCLUSIONS: Respondents viewed injectable PrEP trial participation as a positive experience and a means of enhancing wellbeing. Study site flexibility and affirming clinic environments, inclusive of non-judgemental counselling, were key facilitators of adherence. To support injection persistence, interventions that address structural barriers and promote flexible means of injection delivery may be most effective.

In the ENSEMBLE randomized, placebo-controlled phase 3 trial (NCT04505722), estimated single-dose Ad26.COV2.S vaccine efficacy (VE) was 56% against moderate to severe-critical COVID-19. SARS-CoV-2 Spike sequences were determined from 484 vaccine and 1,067 placebo recipients who acquired COVID-19. In this set of prespecified analyses, we show that in Latin America, VE was significantly lower against Lambda vs. Reference and against Lambda vs. non-Lambda [family-wise error rate (FWER) p

BACKGROUND: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection. METHODS: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7-15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures. FINDINGS: Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05-0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01-0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease. INTERPRETATION: Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection. FUNDING: National Institutes of Health.

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

Background and objectiveAn important barrier to HIV prevention among transgender women (TGW) is the concern that oral pre-exposure prophylaxis (PrEP) negatively affects the efficacy of feminizing hormone therapy (FHT). We aimed to assess the impact of PrEP on FHT pharmacokinetics (PK) among TGW from Brazil.MethodsWe performed a drug-drug interaction sub-study among TGW enrolled in a daily oral PrEP demonstration study (PrEParadas, NCT03220152). Participants had a first PK assessment (PK1) 15 days after FHT (estradiol valerate 2-6 mg plus spironolactone 100-200 mg) initiation and then started PrEP (tenofovir disoproxil fumarate 300 mg/emtricitabine 200 mg). A second PK evaluation was performed 12 weeks later (PK2). Blood samples were collected prior and after the directly observed dosing (0, 0.5, 1, 2, 4, 6, 8, and 24 hours). Pharmacokinetic parameters of estradiol, spironolactone, and metabolites were estimated by non-compartmental analysis (Monolix 2021R2, Lixoft®) and compared as geometric mean ratios (GMRs, 90% confidence interval [CI]).ResultsAmong 19 TGW who completed the substudy, median age was 26 years (interquartile range: 23-27.5). Estradiol area under the plasma concentration-time curve (AUCτ) and trough concentrations did not differ between PK1 and PK2 evaluations (GMR [90% CI]: 0.89 [0.76-1.04] and 1.06 [0.94-1.20], respectively). Spironolactone and canrenone AUCτ were statistically lower at PK2 than PK1 (0.76 [0.65-0.89] and 0.85 [0.78-0.94], respectively). Canrenone maximum concentration was also lower at PK2 than PK1 (0.82 [0.74-0.91]).ConclusionEstradiol PK was not influenced by PrEP concomitant use. The small differences observed in some spironolactone and canrenone PK parameters should not prevent the concomitant use of estradiol-based FHT and PrEP.Trial registrationThis trial (NCT03220152) was registered on July 18, 2017.

Questions remain regarding the effect of baseline host and exposure factors on vaccine efficacy (VE) across pathogens and vaccine platforms. We report placebo-controlled data from four Phase 3 COVID-19 trials during the early period of the pandemic. This was a cross-protocol analysis of four randomized, placebo-controlled efficacy trials (Moderna/mRNA1273, AstraZeneca/AZD1222, Janssen/Ad26.COV2.S, and Novavax/NVX-CoV2373) using a harmonized design. Trials were conducted in the United States and international sites in adults ≥ 18 years of age. VE was assessed for symptomatic and severe COVID-19. We analyzed 114,480 participants from both placebo and vaccine arms, enrolled July 2020 to February 2021, with follow up through July 2021. VE against symptomatic COVID-19 showed little heterogeneity across baseline socio-demographic, clinical or exposure characteristics, in either univariate or multivariate analysis, regardless of vaccine platform. Similarly, VE against severe COVID-19 in the single trial (Janssen) with sufficient endpoints for analysis showed little evidence of heterogeneity. COVID-19 VE is not influenced by baseline host or exposure characteristics across efficacy trials of different vaccine platforms and countries when well matched to circulating virus strains. This supports use of these vaccines, regardless of platform type, as effective tools in the near term for reducing symptomatic and severe COVID-19, particularly for older individuals and those with common co-morbidities during major variant shifts. Clinical trial registration numbers: NCT04470427, NCT04516746, NCT04505722, and NCT04611802.

In the past 20 years, the world has made significant medical progress in addressing HIV. Groundbreaking HIV treatment and prevention options, such as pre‐exposure prophylaxis (PrEP), are increasingly used around [...]

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.

HPTN 083 demonstrated that injectable cabotegravir (CAB) was superior to oral tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) for HIV prevention in cisgender men and transgender women who have sex with men. We previously analyzed 58 infections in the blinded phase of HPTN 083 (16 in the CAB arm and 42 in the TDF-FTC arm). This report describes 52 additional infections that occurred up to 1 year after study unblinding (18 in the CAB arm and 34 in the TDF-FTC arm). Retrospective testing included HIV testing, viral load testing, quantification of study drug concentrations, and drug resistance testing. The new CAB arm infections included 7 with CAB administration within 6 months of the first HIV-positive visit (2 with on-time injections, 3 with ≥1 delayed injection, and 2 who restarted CAB) and 11 with no recent CAB administration. Three cases had integrase strand transfer inhibitor (INSTI) resistance (2 with on-time injections and 1 who restarted CAB). Among 34 CAB infections analyzed to date, diagnosis delays and INSTI resistance were significantly more common in infections with CAB administration within 6 months of the first HIV-positive visit. This report further characterizes HIV infections in persons receiving CAB preexposure prophylaxis and helps define the impact of CAB on the detection of infection and the emergence of INSTI resistance.

BackgroundAge-specific data on anal, and corresponding cervical, human papillomavirus (HPV) infection are needed to inform female anal cancer prevention.MethodsWe centrally reanalyzed individual-level data from 26 studies reporting HPV prevalence in paired anal and cervical samples by human immunodeficiency virus (HIV) status and age. For women with HIV (WWH) with anal high-grade squamous intraepithelial lesions or worse (HSIL+), we also investigated concurrent cervical cytopathology.ResultsIn HIV-negative women, HPV16 prevalence decreased significantly with age, both at anus (4.3% at 15-24 years to 1.0% at ≥55 years; ptrend = 0.0026) and cervix (7.4% to 1.7%; ptrend < 0.0001). In WWH, HPV16 prevalence decreased with age at cervix (18.3% to 7.2%; ptrend = 0.0035) but not anus (11.5% to 13.9%; ptrend = 0.5412). Given anal HPV16 positivity, concurrent cervical HPV16 positivity also decreased with age, both in HIV-negative women (ptrend = 0.0005) and WWH (ptrend = 0.0166). Among 48 WWH with HPV16-positive anal HSIL+, 27 (56%) were cervical high-risk HPV-positive, including 8 with cervical HPV16, and 5 were cervical HSIL+.ConclusionsAge-specific shifts in HPV16 prevalence from cervix to anus suggest that HPV infections in the anus persist longer, or occur later in life, than in the cervix, particularly in WWH. This is an important consideration when assessing the utility of cervical screening results to stratify anal cancer risk.

BackgroundThe 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.MethodsSingle-genome sequencing to detect INSTI RAMs was performed for samples with viral loads

Measuring immune correlates of disease acquisition and protection in the context of a clinical trial is a prerequisite for improved vaccine design. We analysed binding and neutralizing antibody measurements 4 weeks post vaccination as correlates of risk of moderate to severe-critical COVID-19 through 83 d post vaccination in the phase 3, double-blind placebo-controlled phase of ENSEMBLE, an international randomized efficacy trial of a single dose of Ad26.COV2.S. We also evaluated correlates of protection in the trial cohort. Of the three antibody immune markers we measured, we found most support for 50% inhibitory dilution (ID50) neutralizing antibody titre as a correlate of risk and of protection. The outcome hazard ratio was 0.49 (95% confidence interval 0.29, 0.81; P = 0.006) per 10-fold increase in ID50; vaccine efficacy was 60% (43%, 72%) at non-quantifiable ID50 (

: Introduction: HPTN 083 demonstrated the superiority of long‐acting cabotegravir (CAB‐LA) versus daily oral emtricitabine/tenofovir disoproxil fumarate (TDF/FTC) as pre‐exposure prophylaxis (PrEP) among cisgender men and transgender women who have sex with men (MSM/TGW). HPTN 083 provided the first opportunity to understand experiences with injectable PrEP in a clinical trial. Methods: Participants from two US sites (Chicago, IL and Atlanta, GA) and one international site (Rio de Janeiro, Brazil) were purposively sampled for individual qualitative interviews (N = 40), between November 2019 and March 2020, to explore trial experiences, barriers to adherence and other factors that may have impacted study implementation or outcomes. The blinded phase ended early due to efficacy; this analysis includes interviews conducted prior to unblinding with three groups defined by adherence (i.e. injection visit attendance): adherent (n = 27), non‐adherent (n = 12) and early discontinuers (n = 1). Data were organized using NVivo software and analysed using content analysis. Results: Participants (mean age: 27) were primarily cisgender MSM (90%) and Black/African American (60%). Reasons for trial enrolment and PrEP use included a preference for using HIV prevention medication versus treatment in the event of HIV acquisition; the ability to enhance health via study‐related education and services; access to a novel, convenient HIV prevention product at no cost; and contributing to MSM/TGW communities through research. Participants contrasted positive experiences with study staff with their routine clinical care, and emphasized increased scheduling flexibility, thorough communication, non‐judgemental counselling and open, affirming environments (e.g. compassion, less stigma) as adherence facilitators. Injection experiences were positive overall; some described early injection‐related anxiety, which abated with time and when given some measure of control (e.g. pre‐injection countdown), and minimal injection site discomfort. Some concerns and misperceptions about injectable PrEP were reported. Barriers to adherence, across all adherence categories, included structural factors (e.g. financial constraints, travel) and competing demands (e.g. work schedules). Conclusions: Respondents viewed injectable PrEP trial participation as a positive experience and a means of enhancing wellbeing. Study site flexibility and affirming clinic environments, inclusive of non‐judgemental counselling, were key facilitators of adherence. To support injection persistence, interventions that address structural barriers and promote flexible means of injection delivery may be most effective., INTRODUCTION HIV Prevention Trials Network (HPTN) 083 was the first large‐scale, randomized, double‐blind efficacy trial of long‐acting injectable cabotegravir (CAB‐LA) versus daily oral emtricitabine/tenofovir disoproxil fumarate (TDF/FTC) as pre‐exposure prophylaxis [...]

BackgroundWe evaluated in-hospital mortality and outcomes incidence after hospital discharge due to COVID-19 in a Brazilian multicenter cohort.MethodsThis prospective multicenter study (RECOVER-SUS, NCT04807699) included COVID-19 patients hospitalized in public tertiary hospitals in Brazil from June 2020 to March 2021. Clinical assessment and blood samples were performed at hospital admission, with post-hospital discharge remote visits. Hospitalized participants were followed-up until March 31, 2021. The outcomes were in-hospital mortality and incidence of rehospitalization or death after hospital discharge. Kaplan-Meier curves and Cox proportional-hazard models were performed.Findings1589 participants [54.5% male, age=62 (IQR 50-70) years; BMI=28.4 (IQR,24.9-32.9) Kg/m² and 51.9% with diabetes] were included. A total of 429 individuals [27.0% (95%CI,24.8-29.2)] died during hospitalization (median time 14 (IQR,9-24) days). Older age [vs

Purpose of reviewTenofovir-based oral PrEP has been effective in reducing population-level HIV incidence in multiple settings, although disparities remain. Injectable cabotegravir-based PrEP is an alternative that may be attractive to individuals with adherence challenges or who do not desire to take a daily medication. We review promises and challenges of cabotegravir-based PrEP.Recent findingsCabotegravir has demonstrated higher effectiveness than oral PrEP in two randomized trials, with a hazard ratio of 0.31 for HIV incidence among MSM and transgender women across multiple settings [95% confidence interval (CI) 0.18-0.62] and 0.11 for cisgender women in sub-Saharan Africa (95% CI 0.040.32). Cabotegravir was also highly effective among populations with disproportionate HIV incidence. Although cabotegravir breakthrough was rare, diagnosis was delayed with use of antigen/antibody-based HIV tests, and resistance occurred with breakthrough infections. Implementation will need to overcome several challenges, including HIV RNA laboratory monitoring not being widely available, requirement for additional staff time and clinic space, and need to provide oral medication during interruptions in dosing.SummaryCabotegravir-based PrEP is a highly effective additional PrEP option that will expand HIV prevention options. For successful roll-out, strategies for streamlined and accessible delivery of cabotegravir in real-world settings will need to be developed.

BackgroundThe HIV Prevention Trials Network (HPTN) 083 trial demonstrated the superiority of long-acting injectable cabotegravir (CAB-LA) compared with oral emtricitabine-tenofovir disoproxil fumarate (F/TDF) for HIV preexposure prophylaxis (PrEP).ObjectiveTo identify the maximum price premium (that is, greatest possible price differential) that society should be willing to accept for the additional benefits of CAB-LA over tenofovir-based PrEP among men who have sex with men and transgender women (MSM/TGW) in the United States.DesignSimulation, cost-effectiveness analysis.Data sourcesTrial and published data, including estimated HIV incidence (5.32, 1.33, and 0.26 per 100 person-years for off PrEP, generic F/TDF and branded emtricitabine-tenofovir alafenamide (F/TAF), and CAB-LA, respectively); 28% 6-year PrEP retention. Annual base-case drug costs: $360 and $16 800 for generic F/TDF and branded F/TAF. Fewer side effects with branded F/TAF versus generic F/TDF were assumed.Target population476 700 MSM/TGW at very high risk for HIV (VHR).Time horizon10 years.PerspectiveHealth care system.InterventionCAB-LA versus generic F/TDF or branded F/TAF for HIV PrEP.Outcome measuresPrimary transmissions, quality-adjusted life-years (QALYs), costs (2020 U.S. dollars), incremental cost-effectiveness ratios (ICERs; U.S. dollars per QALY), maximum price premium for CAB-LA versus tenofovir-based PrEP.Results of base-case analysisCompared with generic F/TDF (or branded F/TAF), CAB-LA increased life expectancy by 28 000 QALYs (26 000 QALYs) among those at VHR. Branded F/TAF cost more per QALY gained than generic F/TDF compared with no PrEP. At 10 years, CAB-LA could achieve an ICER of at most $100 000 per QALY compared with generic F/TDF at a maximum price premium of $3700 per year over generic F/TDF (CAB-LA price

Understanding the impact of neighborhood context on viral suppression outcomes may help explain health disparities and identify future interventions. We assessed the relationship between individual characteristics, neighborhood socioeconomic context, and viral suppression using multilevel logistic regression models. Adults with HIV initiating antiretroviral therapy (ART) between 2000 and 2017, who resided in Rio de Janeiro and had an HIV-1 RNA level (viral load) measured 90-270 days after ART initiation were included. Overall, 83.9% achieved viral suppression. Participants who were older, had a higher level of education, and identified as heterosexual cisgender men and cisgender men-who-have-sex-with-men had increased odds of viral suppression. Later calendar year of ART initiation carried the strongest association with viral suppression, reflecting the increased effectiveness and tolerability of ART over time. Neighborhood socioeconomic indicators did not predict viral suppression in unadjusted or adjusted analyses, which may result from the integrated care provided in our health care facility together with Brazil's universal treatment.

BackgroundPre-exposure prophylaxis (PrEP) use in Brazil remains low despite free national access. We explored associations of HIV knowledge and internalized homonegativity with PrEP use among PrEP-eligible men who have sex with men (MSM).MethodsBrazilian Hornet users completed an online, cross-sectional survey in February-March 2020. We included cis-men ≥18 years old who reported recent sex with men and were PrEP-eligible per the following: condomless anal intercourse, partner(s) living with HIV, transactional sex, and/or sexually transmitted infection. Our outcome was current PrEP use, defined by the response, "I am currently taking PrEP." Key predictors included the HIV/AIDS Knowledge Assessment (HIV-KA) and Reactions to Homosexuality Scale (RHS); higher scores indicate greater knowledge and greater internalized homonegativity, respectively. Scales were standardized for analysis. Associations with current PrEP use were estimated using adjusted odds ratios (aOR) with 95% confidence intervals (95%CI).FindingsAmong 2398 PrEP-eligible MSM, n = 370 (15·4%) reported current PrEP use. Increasing HIV-KA scores were associated with greater odds of PrEP use (aOR 1·70 [95%CI 1·41-2·04], p < 0·001), and increasing RHS scores with lower odds of PrEP use (aOR 0·83 [95%CI 0·73-0·96], p = 0·010). PrEP use was lower among 18-24 versus 40+-years-old MSM (aOR 0·43 [95%CI 0·27-0·69], p = 0·005), and in Black versus White/Asian respondents (aOR 0·51 [95%CI 0·31-0·85], p = 0·040).InterpretationAmong PrEP-eligible Brazilian MSM, HIV knowledge was associated with increased PrEP use and internalized homonegativity with decreased use. Wider dissemination of HIV prevention knowledge and addressing stigma experienced by MSM could promote increased PrEP use.FundingNational Institute of Mental Health, Fiocruz, Conselho Nacional de Desenvolvimento Científico e Tecnológico.

ObjectiveThe rectal microbiome was examined to assess the relationship between the microbiome and liver disease in HIV-infection.DesignEighty-two HIV-1 mono-infected individuals from the PROSPEC-HIV-study (NCT02542020) were grouped into three liver health categories based on results of controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) of transient elastography: normal (n = 30), steatosis (n = 30), or fibrosis (n = 22).MethodsLiver steatosis and fibrosis were defined by CAP at least 248 dB/m and LSM at least 8.0 kPa, respectively. 16S rRNA gene and whole genome shotgun metagenomic sequencing were performed on rectal swabs. Bacterial differences were assessed using zero-inflated negative binomial regression and random forests modeling; taxonomic drivers of functional shifts were identified using FishTaco.ResultsLiver health status explained four percentage of the overall variation (r2 = 0.04, P = 0.003) in bacterial composition. Participants with steatosis had depletions of Akkermansia muciniphila and Bacteroides dorei and enrichment of Prevotella copri, Finegoldia magna, and Ruminococcus bromii. Participants with fibrosis had depletions of Bacteroides stercoris and Parabacteroides distasonis and enrichment of Sneathia sanguinegens. In steatosis, functional analysis revealed increases in primary and secondary bile acid synthesis encoded by increased Eubacterium rectale, F. magna, and Faecalibacterium prausnitzii and decreased A. muciniphila, Bacteroides fragilis and B. dorei. Decreased folate biosynthesis was driven by similar changes in microbial composition.ConclusionHIV mono-infection with steatosis or fibrosis had distinct microbial profiles. Some taxa are similar to those associated with non-alcoholic fatty liver disease in HIV-negative populations. Further studies are needed to define the role of the gut microbiota in the pathogenesis of liver disease in HIV-infected persons.

: Introduction: Although strong scientific evidence of the efficacy and effectiveness of treatment‐as‐prevention (TasP) is available, full endorsement of the “Undetectable = Untransmittable” (U = U) and “zero‐risk” messages could be improved. Increasing knowledge about HIV transmission, prevention and treatment is a critical component of care efforts. The study assessed knowledge of HIV transmission and prevention strategies, and the perceived accuracy of the slogan U = U among sexual and gender minorities (SGM) in Brazil. Methods: Cross‐sectional web‐based survey targeting adult SGM living in Brazil (2021−2022) recruited on social media and dating apps. We used the 12‐item HIV Knowledge Assessment (HIV‐KA) questionnaire to assess HIV knowledge, three items of which address pre‐exposure prophylaxis (PrEP), post‐exposure prophylaxis and TasP. Perceived accuracy of the U = U slogan was assessed with the question: “With regards to HIV‐positive individuals transmitting HIV through sexual contact, how accurate do you believe the slogan U = U is?”. We a priori grouped the study population into three mutually exclusive groups: people living with HIV (PLHIV), HIV negative and HIV unknown. We used logistic regression models to assess factors associated with high HIV knowledge and perception of the U = U as completely accurate. Results: Of 50,222 individuals accessing the questionnaire, 23,981 were included: 5071 (21.0%) PLHIV, 17,257 (71.5%) HIV negative and 1653 (6.9%) HIV unknown. The proportion of participants with high knowledge was significantly higher for PLHIV and HIV negative (48.1% and 45.5%, respectively) compared to 26.1% of HIV unknown. More PLHIV perceived U = U as completely accurate (80.4%), compared to 60.0% of HIV negative and 42.9% of HIV unknown. HIV knowledge correlates with perceived accuracy of the U = U slogan across all groups. Higher HIV knowledge was associated with higher income and education regardless of HIV status. Among HIV‐negative participants, PrEP awareness and use were associated with higher knowledge and accurate perception of the U = U slogan. Conclusions: Our findings show that HIV knowledge and perceived accuracy of U = U are strongly correlated, that knowledge differs according to HIV status, and that poor socio‐economic is linked to poor knowledge among SGM from Brazil. Educational strategies regarding TasP, U = U and zero risk targeting socio‐economically vulnerable populations are urgent in Brazil., INTRODUCTION Scientific evidence of the efficacy and effectiveness of treatment‐as‐prevention (TasP) has accrued from experimental [1] and large cohort studies [2–4] and were recently summarized in a systematic review that [...]

BackgroundThe HIV Prevention Trials Network (HPTN) 083 trial demonstrated that long-acting cabotegravir (CAB-LA) was more effective than tenofovir disoproxil fumarate-emtricitabine (TDF/FTC) in preventing human immunodeficiency virus (HIV) in cisgender men and transgender women who have sex with men. We characterized HIV infections that occurred in the blinded phase of HPTN 083.MethodsRetrospective testing included HIV testing, viral load testing, quantification of study drugs, and HIV drug resistance testing.ResultsFifty-eight infections were evaluated, including 51 incident infections (12 in CAB arm and 39 in TDF/FTC arm). In many cases (5 in CAB arm and 37 in TDF/FTC arm), infection was associated with low or unquantifiable study drug concentrations. In 4 cases, infection occurred with on-time CAB-LA injections and expected plasma CAB concentrations. CAB exposure was associated with prolonged viral suppression and delayed antibody expression. In some cases, delayed HIV diagnosis resulted in CAB provision to participants with undetected infection, delayed antiretroviral therapy, and emergence of drug resistance; most of these infections would have been detected earlier with viral load testing.ConclusionsEarly detection of HIV infection and prompt antiretroviral therapy initiation could improve clinical outcomes in persons who become infected despite CAB-LA prophylaxis. Further studies are needed to elucidate the correlates of HIV protection in persons receiving CAB-LA.

Two multinational clinical trials have shown safety and efficacy of long-acting injectable cabotegravir for HIV pre-exposure prophylaxis (PrEP). These results will alter the landscape of HIV prevention and related research. Nevertheless, designing and conducting this research involved several ethical issues. This Viewpoint describes how we managed ethical issues over the duration of one of these trials (HPTN 083). Specifically, we discuss the rationale for pursuing a long-acting injectable agent in the presence of effective oral PrEP, trial design choices, site selection and local standards of prevention, data monitoring and early stopping, effects of the COVID-19 pandemic, post-trial access, and assessment of long-term safety.

[This corrects the article DOI: 10.1021/acsptsci.0c00181.].

BackgroundSafe and effective long-acting injectable agents for preexposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) infection are needed to increase the options for preventing HIV infection.MethodsWe conducted a randomized, double-blind, double-dummy, noninferiority trial to compare long-acting injectable cabotegravir (CAB-LA, an integrase strand-transfer inhibitor [INSTI]) at a dose of 600 mg, given intramuscularly every 8 weeks, with daily oral tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) for the prevention of HIV infection in at-risk cisgender men who have sex with men (MSM) and in at-risk transgender women who have sex with men. Participants were randomly assigned (1:1) to receive one of the two regimens and were followed for 153 weeks. HIV testing and safety evaluations were performed. The primary end point was incident HIV infection.ResultsThe intention-to-treat population included 4566 participants who underwent randomization; 570 (12.5%) identified as transgender women, and the median age was 26 years (interquartile range, 22 to 32). The trial was stopped early for efficacy on review of the results of the first preplanned interim end-point analysis. Among 1698 participants from the United States, 845 (49.8%) identified as Black. Incident HIV infection occurred in 52 participants: 13 in the cabotegravir group (incidence, 0.41 per 100 person-years) and 39 in the TDF-FTC group (incidence, 1.22 per 100 person-years) (hazard ratio, 0.34; 95% confidence interval, 0.18 to 0.62). The effect was consistent across prespecified subgroups. Injection-site reactions were reported in 81.4% of the participants in the cabotegravir group and in 31.3% of those in the TDF-FTC group. In the participants in whom HIV infection was diagnosed after exposure to CAB-LA, INSTI resistance and delays in the detection of HIV infection were noted. No safety concerns were identified.ConclusionsCAB-LA was superior to daily oral TDF-FTC in preventing HIV infection among MSM and transgender women. Strategies are needed to prevent INSTI resistance in cases of CAB-LA PrEP failure. (Funded by the National Institute of Allergy and Infectious Diseases and others; HPTN 083 ClinicalTrials.gov number, NCT02720094.).

IntroductionThe HIV Prevention Trials Network (HPTN) 083 trial demonstrated that long-acting cabotegravir (CAB-LA) was more effective than tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) for HIV prevention in cisgender men and transgender women who have sex with men. We characterized HIV infections that occurred in the blinded phase of HPTN 083.MethodsRetrospective testing included HIV testing, viral load testing, quantification of study drugs and HIV drug resistance testing.ResultsFifty-eight infections were evaluated, including 51 incident infections (12 CAB, 39 TDF/FTC). In many cases (5 CAB, 37 TDF/FTC), infection was associated with low or unquantifiable study drug concentrations. In four cases, infection occurred with on-time CAB-LA injections and expected plasma CAB concentrations. CAB exposure was associated with prolonged viral suppression and delayed antibody expression. In some cases, delayed HIV diagnosis resulted in CAB provision to participants with undetected infection, delayed antiretroviral treatment (ART), and emergence of drug resistance; most of these infections would have been detected earlier with viral load testing.ConclusionsEarly detection of HIV infection and prompt ART initiation could improve clinical outcomes in persons who become infected despite CAB-LA prophylaxis. Further studies are needed to elucidate the correlates of HIV protection in persons receiving CAB-LA.