Detection of HIV-1 Transmission Clusters from Dried Blood Spots within a Universal Test-and-Treat Trial in East Africa.

The Sustainable East Africa Research in Community Health (SEARCH) trial was a universal test-and-treat (UTT) trial in rural Uganda and Kenya, aiming to lower regional HIV-1 incidence. Here, we quantify breakthrough HIV-1 transmissions occurring during the trial from population-based, dried blood spot samples. Between 2013 and 2017, we obtained 549 and 488 HIV-1 consensus sequences from 745 participants: 469 participants infected prior to trial commencement and 276 SEARCH-incident infections.

Non-B variants of HIV-1 in San Francisco, California.

The HIV-1 epidemic in the US has historically been dominated by subtype B. HIV subtype diversity has not been extensively examined in most US cities to determine whether non-B variants have become established, as has been observed in many other global regions. We describe the diversity of non-B variants and present evidence of local transmission of non-B HIV in San Francisco.

Everolimus, an mTORC1/2 inhibitor, in ART-suppressed individuals who received solid organ transplantation: A prospective study.

Pharmacologic inhibition of the mammalian target of rapamycin (mTOR) in the setting of renal transplantation has previously been associated with lower human immunodeficiency virus 1 (HIV-1) DNA burden, and in vitro studies suggest that mTOR inhibition may lead to HIV transcriptional silencing. Because prospective clinical trials are lacking, we conducted an open-label, single-arm study to determine the impact of the broad mTOR inhibitor, everolimus, on residual HIV burden, transcriptional gene expression profiles, and immune responses in HIV-infected adult solid organ transplant (SOT) recipients on antiretroviral therapy. Whereas everolimus therapy did not have an overall effect on cell-associated HIV-1 DNA and RNA levels in the entire cohort, participants who maintained everolimus time-averaged trough levels >5 ng/mL during the first 2 months of therapy had significantly lower RNA levels up to 6 months after the cessation of study drug.

The role of drug resistance in poor viral suppression in rural South Africa: findings from a population-based study.

Background: Understanding factors driving virological failure, including the contribution of HIV drug resistance mutations (DRM), is critical to ensuring HIV treatment remains effective. We examine the contribution of drug resistance mutations for low viral suppression in HIV-positive participants in a population-based sero-prevalence survey in rural South Africa.

Methods: We conducted HIV drug resistance genotyping and ART analyte testing on dried blood spots (DBS) from HIV-positive adults participating in a 2014 survey in North West Province.

Antiretroviral Therapy Concentrations Differ in Gut vs. Lymph Node Tissues and Are Associated With HIV Viral Transcription by a Novel RT-ddPCR Assay.

Background: Most HIV-infected cells during antiretroviral therapy (ART) persist in lymphoid tissues. Studies disagree on whether suboptimal tissue ART concentrations contribute to ongoing HIV replication during viral suppression.

Methods: We performed a cross-sectional study in virally-suppressed HIV+ participants measuring lymphoid tissue ART [darunavir (DRV), atazanavir (ATV), and raltegravir (RAL)] concentrations by LC-MS/MS assay.

Impact of Antiretroviral Therapy Duration on HIV-1 Infection of T Cells within Anatomic Sites.

Understanding the impact of antiretroviral therapy (ART) duration on HIV-infected cells is critical for developing successful curative strategies. To address this issue, we conducted a cross-sectional/inter-participant genetic characterization of HIV-1 RNA from pre- and on-therapy plasmas and HIV-1 DNA from CD4 T cell subsets derived from peripheral blood (PB), lymph node (LN), and gut tissues of 26 participants after 3 to 17.8 years of ART.

Memory CD4 + T-Cells Expressing HLA-DR Contribute to HIV Persistence During Prolonged Antiretroviral Therapy.

To date, most assays for measuring the human immunodeficiency virus (HIV-1) reservoir do not include memory CD4+ T-cells expressing the activation marker, human leukocyte antigen-antigen D related (HLA-DR). However, little is known concerning the role these cells play in maintaining persistent HIV-1 during effective antiretroviral therapy (ART). To address this issue, we examined, cellular activation/exhaustion markers (Ki67, CCR5, PD-1, Lag-3 and Tim-3) and viral gag-pol DNA sequences within HLA-DR- and HLA-DR+ memory CD4+ T-cell subsets longitudinally from the peripheral blood of six participants over 3 to ≥15 years of effective therapy.

How are transgender women acquiring HIV? Insights from phylogenetic transmission clusters in San Francisco.

Objective: We explored potential HIV transmission typologies that involve transgender women to obtain insights on sexual and needle-sharing networks as sources of HIV infection.

Design: San Francisco residents diagnosed with HIV in care at public facilities who had available viral pol sequences from June 2001 to January 2016 were included in the analysis.

Methods: Viral sequence data were matched to the San Francisco HIV/AIDS Case Registry to obtain demographic and risk classification information.

HIV Testing and Treatment with the Use of a Community Health Approach in Rural Africa.

Background: Universal antiretroviral therapy (ART) with annual population testing and a multidisease, patient-centered strategy could reduce new human immunodeficiency virus (HIV) infections and improve community health.

Methods: We randomly assigned 32 rural communities in Uganda and Kenya to baseline HIV and multidisease testing and national guideline-restricted ART (control group) or to baseline testing plus annual testing, eligibility for universal ART, and patient-centered care (intervention group). The primary end point was the cumulative incidence of HIV infection at 3 years.

Improvements in the South African HIV care cascade: findings on 90-90-90 targets from successive population-representative surveys in North West Province.

Introduction: To achieve epidemic control of HIV by 2030, countries aim to meet 90-90-90 targets to increase knowledge of HIV-positive status, initiation of antiretroviral therapy (ART) and viral suppression by 2020. We assessed the progress towards these targets from 2014 to 2016 in South Africa as expanded treatment policies were introduced using population-representative surveys.

Methods: Data were collected in January to March 2014 and August to November 2016 in Dr.

Increased uptake of early initiation of antiretroviral therapy and baseline drug resistance testing in San Francisco between 2001 and 2015.

Background: Early initiation of antiretroviral therapy (eiART) can improve clinical outcomes for persons with HIV and reduce onward transmission risk. Baseline drug resistance testing (bDRT) can inform regimen selection upon subsequent treatment initiation. We examined the uptake of eiART and bDRT within 3 months and 30 days of HIV diagnosis.

Beyond Social Desirability Bias: Investigating Inconsistencies in Self-Reported HIV Testing and Treatment Behaviors Among HIV-Positive Adults in North West Province, South Africa.

This mixed-methods study used qualitative interviews to explore discrepancies between self-reported HIV care and treatment-related behaviors and the presence of antiretroviral medications (ARVs) in a population-based survey in South Africa. ARV analytes were identified among 18% of those reporting HIV-negative status and 18% of those reporting not being on ART. Among participants reporting diagnosis over a year prior, 19% reported multiple HIV tests in the past year.

False-positive HIV diagnoses: lessons from Ugandan and Russian research cohorts.

Background: Research studies rely on accurate assessment of entry criteria in order to maintain study integrity and participant safety, however, challenges can exist with HIV studies in international settings.

Objective: Examine the unexpectedly high proportion of study participants with an undetectable HIV viral load found in Ugandan and Russian research cohorts meeting antiretroviral therapy (ART)-naïve entry criteria.

Methods: Russian participants with documented HIV and ART-naïve status were recruited between 2012 and 2015 from clinical and non-clinical sites in St.

HIV-1 persistence following extremely early initiation of antiretroviral therapy (ART) during acute HIV-1 infection: An observational study.

Background: It is unknown if extremely early initiation of antiretroviral therapy (ART) may lead to long-term ART-free HIV remission or cure. As a result, we studied 2 individuals recruited from a pre-exposure prophylaxis (PrEP) program who started prophylactic ART an estimated 10 days (Participant A; 54-year-old male) and 12 days (Participant B; 31-year-old male) after infection with peak plasma HIV RNA of 220 copies/mL and 3,343 copies/mL, respectively. Extensive testing of blood and tissue for HIV persistence was performed, and PrEP Participant A underwent analytical treatment interruption (ATI) following 32 weeks of continuous ART.

Identification of Genetically Intact HIV-1 Proviruses in Specific CD4 T Cells from Effectively Treated Participants.

Latent replication-competent HIV-1 persists in individuals on long-term antiretroviral therapy (ART). We developed the Full-Length Individual Proviral Sequencing (FLIPS) assay to determine the distribution of latent replication-competent HIV-1 within memory CD4 T cell subsets in six individuals on long-term ART. FLIPS is an efficient, high-throughput assay that amplifies and sequences near full-length (∼9 kb) HIV-1 proviral genomes and determines potential replication competency through genetic characterization.

Association of Implementation of a Universal Testing and Treatment Intervention With HIV Diagnosis, Receipt of Antiretroviral Therapy, and Viral Suppression in East Africa.

Importance: Antiretroviral treatment (ART) is now recommended for all HIV-positive persons. UNAIDS has set global targets to diagnose 90% of HIV-positive individuals, treat 90% of diagnosed individuals with ART, and suppress viral replication among 90% of treated individuals, for a population-level target of 73% of all HIV-positive persons with HIV viral suppression.

Objective: To describe changes in the proportions of HIV-positive individuals with HIV viral suppression, HIV-positive individuals who had received a diagnosis, diagnosed individuals treated with ART, and treated individuals with HIV viral suppression, following implementation of a community-based testing and treatment program in rural East Africa.

Population levels and geographical distribution of HIV RNA in rural Ugandan and Kenyan communities, including serodiscordant couples: a cross-sectional analysis.

Background: As sub-Saharan Africa transitions to a new era of universal antiretroviral therapy (ART), up-to-date assessments of population-level HIV RNA suppression are needed to inform interventions to optimise ART delivery. We sought to measure population viral load metrics to assess viral suppression and characterise demographic groups and geographical locations with high-level detectable viraemia in east Africa.

Methods: The Sustainable East Africa Research in Community Health (SEARCH) study is a cluster-randomised controlled trial of an HIV test-and-treat strategy in 32 rural communities in Uganda and Kenya, selected on the basis of rural setting, having an approximate population of 10 000 people, and being within the catchment area of a President's Emergency Plan for AIDS Relief-supported HIV clinic.

Correction: Rapid Progressing Allele HLA-B35 Px Restricted Anti-HIV-1 CD8+ T Cells Recognize Vestigial CTL Epitopes.

[This corrects the article DOI: 10.1371/journal.pone.

Adherence to Pre-Exposure Prophylaxis for HIV Prevention in a Clinical Setting.

Background: The HIV epidemic in the United States (US) disproportionately affects gay, bisexual, and other men who have sex with men (MSM). Pre-exposure prophylaxis (PrEP) using co-formulated tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) has demonstrated high efficacy in reducing HIV incidence among MSM. However, low adherence was reported in major efficacy trials and may present a substantial barrier to successful PrEP implementation.

Increased adolescent HIV testing with a hybrid mobile strategy in Uganda and Kenya.

Objective: We sought to increase adolescent HIV testing across rural communities in east Africa and identify predictors of undiagnosed HIV.

Design: Hybrid mobile testing.

Methods: We enumerated 116 326 adolescents (10-24 years) in 32 communities of Uganda and Kenya (

Search: NCT01864603): 98 694 (85%) reported stable (≥6 months of prior year) residence.

Attrition and Opportunities Along the HIV Care Continuum: Findings From a Population-Based Sample, North West Province, South Africa.

Background: Attrition along the HIV care continuum slows gains in mitigating the South African HIV epidemic. Understanding population-level gaps in HIV identification, linkage, retention in care, and viral suppression is critical to target programming.

Methods: We conducted a population-based household survey, HIV rapid testing, point-of-care CD4 testing, and viral load measurement from dried blood spots using multistage cluster sampling in 2 subdistricts of North West Province from January to March, 2014.

A hybrid mobile approach for population-wide HIV testing in rural east Africa: an observational study.

Background: Despite large investments in HIV testing, only an estimated 45% of HIV-infected people in sub-Saharan Africa know their HIV status. Optimum methods for maximising population-level testing remain unknown. We sought to show the effectiveness of a hybrid mobile HIV testing approach at achieving population-wide testing coverage.