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BackgroundOral pre-exposure prophylaxis (PrEP) with emtricitabine/tenofovir disoproxil fumarate (F/TDF) has high efficacy against HIV-1 acquisition. Seventy-two prospective studies of daily oral F/TDF PrEP were conducted to evaluate HIV-1 incidence, drug resistance, adherence, and bone and renal safety in diverse settings.MethodsHIV-1 incidence was calculated from incident HIV-1 diagnoses after PrEP initiation and within 60 days of discontinuation. Tenofovir concentrations in dried blood spots (DBS), drug resistance, and bone/renal safety indicators were evaluated in a subset of studies.ResultsAmong 17 274 participants, there were 101 cases with new HIV-1 diagnosis (.77 per 100 person-years; 95% confidence interval [CI]: .63-.94). In 78 cases with resistance data, 18 (23%) had M184I or V, 1 (1.3%) had K65R, and 3 (3.8%) had both mutations. In 54 cases with tenofovir concentration data from DBS, 45 (83.3%), 2 (3.7%), 6 (11.1%), and 1 (1.9%) had average adherence of

During January-August 2021, the Community Prevalence of SARS-CoV-2 Study used time/location sampling to recruit a cross-sectional, population-based cohort to estimate SARS-CoV-2 seroprevalence and nasal swab sample PCR positivity across 15 [...]

ObjectiveHIV Prevention Trials Network 069/AIDS Clinical Trials Group A5305 was a study of 48-week oral pre-exposure prophylaxis (PrEP) regimens in MSM and transgender women. A rectal substudy was included to evaluate drug concentrations in rectal compartment vs. blood, gut-associated lymphoid tissue (GALT) responses to four antiretroviral PrEP regimens [maraviroc (MVC), MVC + emtricitabine (FTC), MVC + tenofovir (TFV) disoproxil fumarate, and TFV disoproxil fumarate + FTC], and to determine whether ARV exposure was associated with ex-vivo suppression of HIV infection in colorectal explants.MethodsC-C chemokine receptor type 5 (CCR5) genotype was characterized using PCR. At baseline and at Weeks 24, 48, and 49, GALT phenotype was characterized by flow cytometry, rectal biopsies were challenged with HIV-1BaL, and tissue and plasma pharmacokinetics were measured via mass spectrometry.ResultsExposure to MVC was not associated with increased expression of CD4+/CCR5+ HIV target T cells. Significant ex-vivo viral suppression compared with baseline was seen at Weeks 24 and 48, ranging from 1.4 to 1.8 log10 for all study regimens except the MVC-alone arm which did not show statistically significant viral suppression at Week 48. Tissue concentrations of TFV, TFV-diphosphate, and FTC were correlated with viral suppression.ConclusionMVC-containing HIV PrEP regimens did not increase GALT CD4+ T-cell activation or the CD4+/CCR5+ phenotype. No virologic suppression was seen with MVC-alone at Week 48 compared with combination regimens, suggesting MVC monotherapy might be less effective than combination antiretroviral PrEP regimens.

OBJECTIVE:HIV Prevention Trials Network 069/AIDS Clinical Trials Group A5305 was a study of 48-week oral pre-exposure prophylaxis (PrEP) regimens in MSM and transgender women. A rectal substudy was included to evaluate drug concentrations in rectal compartment vs. blood, gut-associated lymphoid tissue (GALT) responses to four antiretroviral PrEP regimens [maraviroc (MVC), MVC + emtricitabine (FTC), MVC + tenofovir (TFV) disoproxil fumarate, and TFV disoproxil fumarate + FTC], and to determine whether ARV exposure was associated with ex-vivo suppression of HIV infection in colorectal explants. METHODS:C-C chemokine receptor type 5 (CCR5) genotype was characterized using PCR. At baseline and at Weeks 24, 48, and 49, GALT phenotype was characterized by flow cytometry, rectal biopsies were challenged with HIV-1BaL, and tissue and plasma pharmacokinetics were measured via mass spectrometry. RESULTS:Exposure to MVC was not associated with increased expression of CD4/CCR5 HIV target T cells. Significant ex-vivo viral suppression compared with baseline was seen at Weeks 24 and 48, ranging from 1.4 to 1.8 log10 for all study regimens except the MVC-alone arm which did not show statistically significant viral suppression at Week 48. Tissue concentrations of TFV, TFV-diphosphate, and FTC were correlated with viral suppression. CONCLUSION:MVC-containing HIV PrEP regimens did not increase GALT CD4 T-cell activation or the CD4/CCR5 phenotype. No virologic suppression was seen with MVC-alone at Week 48 compared with combination regimens, suggesting MVC monotherapy might be less effective than combination antiretroviral PrEP regimens.

Introduction: There is an urgent need to identify men who have sex with men (MSM) living with HIV with unsuppressed viral loads to prevent transmission. Though respondent-driven sampling (RDS) is traditionally used for hard-to-reach populations, we compare how RDS and direct recruitment (DR) perform in identifying MSM living with HIV with unsuppressed viralloads and identifying MSM with socio-demographics characteristic of hard-to-reach populations. Methods: This is a cross-sectionalanalysis among 1305 MSM who were recruited from March 2016 to December 2017 for a case management intervention trial(HPTN 078). We recruited participants across four cities using RDS and DR methods: Birmingham, AL; Atlanta, GA; Baltimore, MD; and Boston, MA. Participants completed a socio-demographic questionnaire and underwent HIV testing. We compare the proportion of MSM with HIV and unsuppressed viralloads (HIV RNA [greater than or equal to] 1000 copies/ml) based on recruitment method using Pearson chi-square tests. We also compare differences in race, income, healthcare coverage, education, sexual orientation, hidden sexuality and comfort with participating in the LGBT community between recruitment methods and perform non-parametric trend tests to see how demographics change across RDS recruitment waves. Results: RDS recruited 721 men (55.2%) and DR yielded 584 men (44.8%). Overall, 69% were living with HIV, of whom 18% were not virally suppressed. HIV prevalence was higher among those recruited via DR (84%) compared to RDS (58%), p < 0.0001. Twenty per cent of DR recruits were not virally suppressed compared to 15% of RDS, though this was not significant. DR yielded a significantly higher proportion of Black participants and those with less than a high school diploma. The prevalence of low income, no healthcare coverage, bisexuality and hidden sexuality increased across RDS waves. Conclusions: DR was more efficient in identifying MSM living with HIV with unsuppressed viral loads; however, there was a higher proportion of hard-to-reach MSM who were low income, lacked health coverage, were bisexual and were not open with their sexuality in deeper waves of RDS. Researchers should consider supplementing RDS recruitment with DR efforts if aiming to identify MSM with unsuppressed viral loads via RDS. Keywords: ARV; co-infection; HIV epidemiology; men who have sex with men; recruitment; viral suppression, 1 | INTRODUCTION The HIV epidemic in the United States has disproportionately affectedgay,bisexual and other men who have sex with men (MSM) since the first cases were identified in the [...]

BackgroundMaraviroc (MVC) is a candidate for human immunodeficiency virus (HIV) pre-exposure prophylaxis.MethodsPhase 2 48-week safety/tolerability study was conducted, comparing 4 regimens: MVC alone, MVC plus emtricitabine (FTC), MVC plus tenofovir disoproxil fumarate (TDF), and TDF plus FTC. Eligible participants were HIV-uninfected men and transgender women reporting condomless anal intercourse with ≥1 HIV-infected or unknown-serostatus man within 90 days. At each visit, assessments, laboratory testing, and counseling were done. Analyses were intention to treat.ResultsAmong 406 participants, 84% completed follow-up, 7% stopped early, and 9% were lost to follow-up; 9% discontinued their regimen early. The number discontinuing and the time to discontinuation did not differ among study regimens (P = .60). Rates of grade 3-4 adverse events did not differ among regimens (P = .37). In a randomly selected subset, 77% demonstrated detectable drug concentrations at week 48. Five participants acquired HIV infection (4 MVC alone, 1 MVC + TDF; overall annualized incidence, 1.4% [95% confidence interval, .5%-3.3%], without differences by regimen; P = .32); 2 had undetectable drug concentrations at every visit, 2 had low concentrations at the seroconversion visit, and 1 had variable concentrations.ConclusionsMVC-containing regimens were safe and well tolerated compared with TDF + FTC; this study was not powered for efficacy. Among those acquiring HIV infection, drug concentrations were absent, low, or variable. MVC-containing regimens may warrant further study for pre-exposure prophylaxis.Clinical trials registrationNCT01505114.

Introduction: HIV prevalence is high among men who have sex with men (MSM) in Baltimore, Maryland, United States, and the levels of viral suppression among HIV-positive MSM are relatively low. The HIV Prevention Trials Network 078 trial seeks to increase the levels of viral suppression among US MSM by increasing the rates of diagnosis and linkage to care and treatment. We estimated the increases in viral suppression needed to reach different HIV incidence reduction targets, and the impact of meeting diagnosis and treatment targets. Methods: We used a mathematical model of HIV transmission among MSM from Baltimore, US, parameterised with behavioural data and fitted to HIV prevalence and care continuum data for Baltimore wherever possible, to project increases in viral suppression needed to reduce the HIV incidence rate among Baltimore MSM by 10, 20, 30 or 50% after 2, 5 and 10 years. We also projected HIV incidence reductions achieved if US national targets--90% of people living with HIV (PLHIV) know their HIV serostatus, 90% of those diagnosed are retained in HIV medical care and 80% of those diagnosed are virally suppressed--or UNAIDS 90-90-90 targets (90% of PLHIV know their status, 90% of those diagnosed receive antiretroviral therapy (ART), 90% of those receiving ART are virally suppressed) are each met by 2020. Results: To reduce the HIV incidence rate by 20% and 50% after five years (compared with the base-case at the same time point), the proportion of all HIV-positive MSM who are virally suppressed must increase above 2015 levels by a median 13 percentage points (95% uncertainty interval 9 to 16 percentage points) from median 49% to 60%, and 27 percentage points (22 to 35) from 49% to 75% respectively. Meeting all three US or 90-90-90 UNAIDS targets results in a 48% (31% to 63%) and 51% (38% to 65%) HIV incidence rate reduction in 2020 respectively. Conclusions: Substantial improvements in levels of viral suppression will be needed to achieve significant incidence reductions among MSM in Baltimore, and to meet 2020 US and UNAIDS targets. Future modelling studies should additionally consider the impact of pre-exposure prophylaxis for MSM. Keywords: HIV infections; incidence; homosexuality, male; models, theoretical; United States; forecasting, 1 | INTRODUCTION HIV incidence and prevalence remain high among gay, bisexual and other men who have sex with men (MSM) in the United States (US) [1-3]. Baltimore, Maryland (population [...]