Safety, Tolerability, and Pharmacokinetics of Long-Acting Broadly Neutralizing HIV-1 Monoclonal Antibody VRC07523LS in Newborn Infants Exposed to HIV-1.

Background: Vertical HIV-1 transmission despite antiretroviral therapy may be mitigated by use of long-acting, broadly neutralizing, monoclonal antibodies (bNAb) such as VRC07523LS. The present study was designed to determine the safety and pharmacokinetics of VRC07523LS.

Methods: VRC07523LS, 80 mg/dose, was administered subcutaneously after birth to non-breastfed (Cohort 1; N=11, enrolled in USA) and breastfed (Cohort 2; N=11, enrolled in South Africa and Zimbabwe) infants exposed to HIV-1.

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.

Prevalence of detectable HIV-DNA and HIV-RNA in cerebrospinal fluid of youth with perinatal HIV and impaired cognition on antiretroviral therapy.

Objective: Central nervous system (CNS) HIV infection can impact cognition and may be an obstacle to cure in adolescents and young adults with perinatal HIV (AYAPHIV). IMPAACT2015 enrolled AYAPHIV on suppressive antiretroviral therapy (ART) with cognitive impairment to detect and quantify HIV in blood and cerebrospinal fluid (CSF).

Design: IMPAACT2015 was a U.

"It's already in your body and it's preventing": a qualitative study of African female adolescent's acceptability and preferences for proxy HIV prevention methods in Cape Town, South Africa.

Background: Advances in biomedical HIV prevention will soon offer young women a choice of HIV prevention methods, including various pre-exposure prophylaxis (PrEP) modalities such as daily oral pills, dapivirine vaginal ring, and long-acting injectable agents. By understanding preferences for contraceptive methods, we may draw analogies for the HIV prevention needs of young women. The UChoose Study was an open-label randomised cross-over study designed to evaluate the acceptability and preference for several contraceptive options as a proxy for HIV prevention methods that use similar types of administration.

A Randomized Trial of Point-of-Care Early Infant Human Immunodeficiency Virus (HIV) Diagnosis in Zambia.

Background: Point-of-care (POC) early infant diagnosis (EID) provides same-day results and the potential for immediate initiation of antiretroviral therapy (ART).

Methods: We conducted a pragmatic trial at 6 public clinics in Zambia. HIV-exposed infants were individually randomized to either (1) POC EID (onsite testing with the Alere q HIV-1/2 Detect) or (2) enhanced standard of care (SOC) EID (off-site testing at a public laboratory).

Safety, acceptability, and pharmacokinetics of a monoclonal antibody-based vaginal multipurpose prevention film (MB66): A Phase I randomized trial.

Background: MB66 film is a multipurpose prevention technology (MPT) product with monoclonal antibodies (mAbs) against HIV-1 (VRC01-N) and HSV-1 and 2 (HSV8-N). The mAbs were produced by transient expression in Nicotiana benthamiana (N). We conducted a Phase I clinical trial to assess the safety, pharmacokinetics (PK), and ex vivo efficacy of single and repeated doses of MB66 when used intravaginally.

Tenofovir Diphosphate Concentrations in Dried Blood Spots From Pregnant and Postpartum Adolescent and Young Women Receiving Daily Observed Pre-exposure Prophylaxis in Sub-Saharan Africa.

Background: Intracellular tenofovir diphosphate (TFV-DP) concentration in dried blood spots (DBSs) is used to monitor cumulative pre-exposure prophylaxis (PrEP) adherence. We evaluated TFV-DP in DBSs following daily oral PrEP (emtricitabine 200 mg/tenofovir diphosphate 300 mg) among pregnant and postpartum adolescent girls and young women (AGYW).

Methods: Directly observed PrEP was administered for 12 weeks in a pregnancy (14-24 weeks' gestation, n = 20) and postpartum (6-12 weeks postpartum, n = 20) group of AGYW aged 16-24 years in sub-Saharan Africa.

Acceptability, safety, and patterns of use of oral tenofovir disoproxil fumarate and emtricitabine for HIV pre-exposure prophylaxis in South African adolescents: an open-label single-arm phase 2 trial.

Background: HIV incidence among adolescents in southern Africa remains unacceptably high. Pre-exposure prophylaxis (PrEP) is an effective HIV prevention intervention but there are few data on its implementation among adolescents. We aimed to investigate the safety, feasibility, and acceptability of PrEP with oral tenofovir disoproxil fumarate and emtricitabine as part of a comprehensive HIV prevention package in an adolescent population in South Africa.

An open-label, randomized crossover study to evaluate the acceptability and preference for contraceptive options in female adolescents, 15 to 19 years of age in Cape Town, as a proxy for HIV prevention methods (UChoose).

Introduction: Young women in Southern Africa have extremely high HIV incidence rates necessitating the availability of female-controlled prevention methods. Understanding adolescent preference for seeking contraception would improve our understanding of acceptability, feasibility and adherence to similar modes of delivery for HIV prevention.

Methods: UChoose was an open-label randomized crossover study over 32 weeks which aimed to evaluate the acceptability and preference for contraceptive options in healthy, HIV-uninfected, female adolescents aged 15 to 19 years, as a proxy for similar HIV prevention methods.

Factors Associated With Poor Linkage to Human Immunodeficiency Virus Care Among Index Clients and Sex Partners Receiving Human Immunodeficiency Virus Assisted Partner Services in Kenya.

Introduction: Human immunodeficiency virus (HIV) assisted partner services (aPS) has been recommended as a strategy to increase HIV case finding. We evaluated factors associated with poor linkage to HIV care among newly diagnosed HIV-positive individuals (index clients) and their partners after receiving aPS in Kenya.

Methods: In a cluster randomized trial conducted between 2013 and 2015, 9 facilities were randomized to immediate aPS (intervention).

Safety and Efficacy of 48 and 96 Weeks of Alendronate in Children and Adolescents With Perinatal Human Immunodeficiency Virus Infection and Low Bone Mineral Density for Age.

No safety concerns were identified in a randomized, crossover study of alendronate/placebo in youth with perinatal HIV infection and low bone mineral density (BMD). BMD improved with 48 weeks of alendronate and continued to improve with an additional 48 weeks of therapy. Gains were largely maintained 48 weeks after stopping alendronate.

Alendronate Improves Bone Mineral Density in Children and Adolescents Perinatally Infected With Human Immunodeficiency Virus With Low Bone Mineral Density for Age.

Background: Children and adolescents with perinatal human immunodeficiency virus (HIV) infection and with low bone mineral density (BMD) may be at higher risk of osteoporosis and fractures in later life than their uninfected peers. Bisphosphonate therapy has been shown to reduce fractures in adults with osteoporosis, but has not been formally studied in youths living with HIV.

Methods: Fifty-two children and adolescents (aged 11-24 years) perinatally infected with HIV with low lumbar spine (LS) BMD (Z score < -1.

Index participant characteristics and HIV assisted partner services efficacy in Kenya: results of a cluster randomized trial.

Introduction: We have previously demonstrated that assisted partner services (aPS) increases HIV testing and case finding among partners of persons living with HIV (PLHIV) in a cluster randomized trial in Kenya. However, the efficacy of aPS may vary across populations. In this analysis, we explore differences in aPS efficacy by characteristics of index participants.

Tenofovir disoproxil fumarate intravaginal ring for HIV pre-exposure prophylaxis in sexually active women: a phase 1, single-blind, randomised, controlled trial.

Background: An intravaginal ring that releases the tenofovir prodrug, tenofovir disoproxil fumarate, provided 100% protection in macaques against simian HIV and was safe in a 14-day clinical trial in sexually abstinent women. We aimed to assess the safety and pharmacokinetics of this intravaginal ring over 90 days in sexually active women.

Methods: We did a phase 1, single-blind, randomised, placebo-controlled trial to assess safety, pharmacokinetics, and acceptability of a tenofovir disoproxil fumarate intravaginal ring used continuously with monthly ring changes for 3 months.

FAME-04: A Phase 1 trial to assess the safety, acceptability, pharmacokinetics and pharmacodynamics of film and gel formulations of tenofovir.

Introduction: Fast-dissolving vaginal film formulations release antiretroviral drugs directly into vaginal fluid and may be as efficient at drug delivery yet more acceptable to women than gels. In this Phase 1 vaginal film study, the safety, acceptability, pharmacokinetics and pharmacodynamics of two doses of tenofovir (TFV) film and TFV 1% gel were compared to corresponding placebo formulations.

Methods: Seventy-eight healthy HIV negative women were randomized to self-insert daily vaginal film (10 mg TFV, 40 mg TFV or placebo) or 4 mL of vaginal gel (TFV 1% [40 mg] or placebo) for seven days.

Brief Report: HIV Assisted Partner Services Among Those With and Without a History of Intimate Partner Violence in Kenya.

Background: HIV assisted partner services (APS) are a notification and testing strategy for sex partners of HIV-infected index patients. This cluster-randomized controlled trial secondary data analysis investigated whether history of intimate partner violence (IPV) modified APS effectiveness and risk of relationship dissolution.

Setting: Eighteen HIV testing and counseling sites in Kenya randomized to provide immediate APS (intervention) or APS delayed for 6 weeks (control).

Comparison of the Pharmacokinetics and Pharmacodynamics of Single-Dose Tenofovir Vaginal Film and Gel Formulation (FAME 05).

Objective: Although preexposure prophylaxis with oral tenofovir (TFV) disoproxil fumarate/emtricitabine reduces HIV acquisition rates, poor adherence to and acceptability of daily vaginal gels have led to development of vaginal film formulations to improve adherence and, potentially, to enable episodic use.

Study Design: In this 2-arm, cross-over study of a fast-dissolving tenofovir film (40 mg) compared with a previously studied semisolid tenofovir 1% gel (40 mg), 10 healthy women received a single vaginal dose of each study product. Clinical, pharmacokinetic, and antiviral assessments were performed over 1 week after dose.

Assisted partner notification services are cost-effective for decreasing HIV burden in western Kenya.

Background: Assisted partner services (aPS) or provider notification for sexual partners of persons diagnosed HIV positive can increase HIV testing and linkage in Sub-Saharan Africa and is a high yield strategy to identify HIV-positive persons. However, its cost-effectiveness is not well evaluated.

Methods: Using effectiveness and cost data from an aPS trial in Kenya, we parameterized an individual-based, dynamic HIV transmission model.