Cabotegravir pharmacokinetics in Asians with and without HIV.

Objective: Cabotegravir is approved for HIV treatment (with rilpivirine) and prevention. The established cabotegravir population pharmacokinetic (PPK) model included 1.2% Asian participants.

Bone Changes With Long-Acting Cabotegravir or Tenofovir Disoproxil Fumarate/Emtricitabine for HIV Prevention in Cisgender Men and Transgender Women: HPTN 083.

In a randomized clinical trial, pre-exposure prophylaxis (PrEP) with long-acting cabotegravir (CAB-LA) had a better bone safety profile than tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) over 105 weeks. For individuals with low bone mineral density or other fracture risk factors, CAB-LA PrEP should be considered over TDF-based PrEP. Clinical Trials Registration.

Virologic effects of broadly neutralizing antibodies VRC01LS and VRC07-523LS on chronic HIV-1 infection.

BACKGROUNDHIV-1-specific broadly neutralizing monoclonal antibodies (bNAbs) have emerged as promising interventions with the potential to effectively treat and prevent HIV-1 infections. We conducted a phase I clinical trial evaluating the potent CD4-binding site-specific (CD4bs-specific) bNAbs VRC01LS and VRC07-523LS in people with HIV-1 (PWH) not receiving antiretroviral therapy (ART).METHODSParticipants received a single intravenous 40 mg/kg dose of either VRC01LS (n = 7) or VRC07-523LS (n = 9) and did not initiate ART for a minimum of 14 days.

Update on HIV Chemoprevention.

Despite rapid advances in the field of HIV prevention and treatment, unacceptably high global HIV incidence rates highlight the ongoing need for effective HIV prevention interventions for populations at risk for HIV acquisition. This article provides an updated review of the current data surrounding HIV prevention strategies, including treatment as prevention (TasP), preexposure prophylaxis (PrEP), and postexposure prophylaxis (PEP), as well as advances in sexually transmitted infection biomedical prevention. This review provides an overview of the multiple PrEP modalities that are available globally, such as oral PrEP, injectable cabotegravir, and the dapivirine vaginal ring, and describes their respective clinical trials, efficacies, and regulatory approvals.

Comparative- and Cost-Effectiveness Research Determining the Optimal Intervention for Advancing Transgender Women With HIV to Full Viral Suppression (Text Me, Alexis!): Protocol for a Randomized Controlled Trial.

Background: Many transgender women with HIV achieve suboptimal advancement through the HIV Care Continuum, including poor HIV health care usage, retention in HIV medical care, and rates of viral suppression. These issues are exacerbated by comorbid conditions, such as substance use disorder, which is also associated with reduced quality of life, increased overdose deaths, usage of high-cost health care services, engagement in a street economy, and cycles of incarceration. Thus, it is critical that efforts to End the HIV Epidemic include effective interventions to link and retain transgender women in HIV care through full viral suppression.

Safety, tolerability, pharmacokinetics, and neutralisation activities of the anti-HIV-1 monoclonal antibody PGT121.414.LS administered alone and in combination with VRC07-523LS in adults without HIV in the USA (HVTN 136/HPTN 092): a first-in-human, open-label, randomised controlled phase 1 trial.

Background: Multiple broadly neutralising monoclonal antibodies (mAbs) are in development for HIV-1 prevention. The aim of this trial was to test the PGT121.414.

Cabotegravir Maintains Protective Efficacy in the Setting of Bacterial STIs: A Secondary Analysis of HPTN 083.

Background: Sexually transmitted infections (STIs) have been shown to facilitate HIV transmission and acquisition. HPTN 083, a global clinical trial, demonstrated superiority of long-acting cabotegravir (CAB-LA) versus daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) for HIV prevention among transgender women and cisgender men who have sex with men. This analysis assessed whether CAB-LA maintained protective efficacy when bacterial STIs (syphilis, rectal/urethral gonorrhea and chlamydia) were present.

Protocol for a randomized controlled trial with a stepped care approach, utilizing PrEP navigation with and without contingency management, for transgender women and sexual minority men with a substance use disorder: Assistance Services Knowledge-PrEP (A.S.K.-PrEP).

Background: In the United States, most (~ 70%) annual newly diagnosed HIV infections are among substance-using sexual minority men (SMM) and gender minority transgender women (trans women). Trans women and SMM are more likely to report or be diagnosed with a substance use disorder (SUD) than their cisgender or heterosexual counterparts and the presence of an SUD substantially increases the risk of HIV infection in both groups. Although Pre-Exposure Prophylaxis (PrEP) is highly effective, initiation, adherence, and persistence are exclusively behavioral outcomes; thus, the biomedical benefits of PrEP are abrogated by substance use.

HIV DNA Levels in Persons Who Acquired HIV in the Setting of Long-Acting Cabotegravir for HIV Prevention: Analysis of Cases from HPTN 083 and 084.

We evaluated HIV DNA levels in individuals who received long-acting cabotegravir (CAB-LA) or tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) pre-exposure prophylaxis in the HPTN 083 and 084 trials and had HIV DNA testing performed to help determine HIV status. HIV DNA testing was performed using peripheral blood mononuclear cell (PBMC) samples collected after a reactive HIV test was obtained at a study site. DNA was quantified using droplet digital PCR (lower limit of detection [LLOD]: 4.

Pharmacologic Drug Detection and Self-Reported Adherence in the HPTN069/ACTG5305 Phase II PrEP Trial.

Adherence drives efficacy in PrEP clinical trials. We compared drug concentrations and self-reported adherence in HPTN069/ACTG5305, a double-blinded, randomized trial of the safety and tolerability of candidate PrEP regimens that included maraviroc (MVC), tenofovir (TDF), and emtricitabine (FTC). Plasma drug concentrations and self-reported adherence by computer-assisted self-interview (CASI) were assessed at study weeks 24 and 48.

Evaluation of Xpert point-of-care assays for detection of HIV infection in persons using long-acting cabotegravir for pre-exposure prophylaxis.

Unlabelled: Detection of HIV infection may be challenging in persons using long-acting cabotegravir (CAB-LA) pre-exposure prophylaxis (PrEP) due to viral suppression and reduced/delayed antibody production. We evaluated two point-of-care tests for detecting HIV infection in persons who received CAB-LA in the HPTN 083 trial. Samples were obtained from 12 participants who received CAB-LA and had delayed detection of HIV infection using HIV rapid tests and an antigen/antibody test (52 plasma samples; 18 dried blood spot [DBS] samples).

The impact of intimate partner violence on PrEP adherence among U.S. Cisgender women at risk for HIV.

Background: Cisgender women account for 1 in 5 new HIV infections in the United States, yet remain under-engaged in HIV prevention. Women experiencing violence face risk for HIV due to biological and behavioral mechanisms, and barriers to prevention, such as challenges to Pre-Exposure Prophylaxis for HIV Prevention (PrEP) adherence. In this analysis, we aim to characterize intimate partner violence (IPV) among cisgender heterosexual women enrolled in a PrEP demonstration project and assess the associations with PrEP adherence.

HPTN 083-02: factors influencing adherence to injectable PrEP and retention in an injectable PrEP study.

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.

Long-acting cabotegravir pharmacokinetics with and without oral lead-in for HIV PrEP.

Unlabelled: Long-acting cabotegravir is approved for pre-exposure prophylaxis and combination HIV treatment, both initiated with optional short-term oral lead-in (OLI). We evaluated the impact of OLI on long-acting cabotegravir pharmacokinetics. Cabotegravir plasma concentrations were compared between HIV-positive participants initiating injections with ( = 278) or without ( = 110) OLI in phase III treatment study FLAIR and in HIV-negative participants using OLI ( = 263) in pivotal pre-exposure prophylaxis studies HPTN 083 and HPTN 084.

Type 1 Human Immunodeficiency Virus (HIV-1) Incidence, Adherence, and Drug Resistance in Individuals Taking Daily Emtricitabine/Tenofovir Disoproxil Fumarate for HIV-1 Pre-exposure Prophylaxis: Pooled Analysis From 72 Global Studies.

Background: Oral 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.

Methods: HIV-1 incidence was calculated from incident HIV-1 diagnoses after PrEP initiation and within 60 days of discontinuation.

Efficacy and safety of long-acting cabotegravir compared with daily oral tenofovir disoproxil fumarate plus emtricitabine to prevent HIV infection in cisgender men and transgender women who have sex with men 1 year after study unblinding: a secondary analysis of the phase 2b and 3 HPTN 083 randomised controlled trial.

Background: Injectable cabotegravir was superior to daily oral tenofovir disoproxil fumarate plus emtricitabine for HIV prevention in two clinical trials. Both trials had the primary aim of establishing the HIV prevention efficacy of long-acting injectable cabotegravir pre-exposure prophylaxis (PrEP) compared with tenofovir disoproxil fumarate plus emtricitabine daily oral PrEP. Long-acting PrEP was associated with diagnostic delays and integrase strand-transfer inhibitor (INSTI) resistance.

Daily Oral HIV Pre-exposure Prophylaxis Among Young Men Who Have Sex With Men in the United States: Cost-saving at Generic Drug Price.

Background: Adherence and retention concerns raise questions about the effectiveness and cost-effectiveness of oral HIV pre-exposure prophylaxis (PrEP) in young men who have sex with men (YMSM).

Methods: Using an adolescent-focused simulation model, we compared annual HIV screening alone with tenofovir disoproxil fumarate/emtricitabine-based oral PrEP with every 3-month HIV screening in YMSM (aged 15-24) at increased risk of HIV. Data derived from published sources included: age-stratified HIV incidence/100 person-years (PY) on- or off-PrEP (0.

Efficacy, safety, tolerability, and pharmacokinetics of long-acting injectable cabotegravir for HIV pre-exposure prophylaxis in transgender women: a secondary analysis of the HPTN 083 trial.

Background: The HIV Prevention Trials Network (HPTN) 083 trial showed that long-acting injectable cabotegravir was more effective than tenofovir disoproxil fumarate plus emtricitabine in preventing HIV in cisgender men and transgender women who have sex with men. We aimed to characterise the cohort of transgender women included in HPTN 083.

Methods: HPTN 083 is an ongoing, phase 2b/3, randomised, multicentre, double-blind, double-dummy clinical trial done at 43 sites in seven countries (Argentina, Brazil, Peru, the USA, South Africa, Thailand, and Viet Nam).

Breakthrough HIV-1 infection in setting of cabotegravir for HIV pre-exposure prophylaxis.

Objective: We describe the first case of HIV-1 infection in the setting of long-acting injectable cabotegravir (CAB-LA) for HIV pre-exposure prophylaxis to occur in the real world.

Design: Case report.

Methods: Electronic medical records were reviewed to assess patient history and CAB-LA administration details.

Prevention, treatment and cure of HIV infection.

The development of antiretroviral therapy for the prevention and treatment of HIV infection has been marked by a series of remarkable successes. However, the efforts to develop a vaccine have largely failed, and efforts to discover a cure are only now beginning to gain traction. In this Review, we describe recent progress on all fronts - pre-exposure prophylaxis, vaccines, treatment and cure - and we discuss the unmet needs, both current and in the coming years.