Pharmacokinetics and safety of coformulated bictegravir, emtricitabine, and tenofovir alafenamide in children aged 2 years and older with virologically suppressed HIV: a phase 2/3, open-label, single-arm study.

Background: Coformulated bictegravir, emtricitabine, and tenofovir alafenamide is a single-tablet regimen and was efficacious and well tolerated in children and adolescents with HIV (aged 6 years to <18 years) in a 48-week phase 2/3 trial. In this study, we report data from children aged at least 2 years and weighing 14 kg to less than 25 kg.

Methods: We conducted this open-label, multicentre, multicohort, single-arm study in South Africa, Thailand, Uganda, and the USA.

Infection prevention and control and related practices in African neonatal units: The Pan-African neonatal care assessment study (PANCAS).

Background: The burden of neonatal mortality is primarily borne by low- and middle-income countries (LMICs), including deaths due to healthcare-associated infections (HAIs). Few studies have assessed infection prevention and control (IP&C) practices in African units caring for small and/or sick newborns aimed to reduce HAIs.

Methods: We performed a mixed-methods study composed of a survey and virtual tour to assess IP&C and related practices.

Higher CCR5 density on CD4 + T-cells in mothers and infants is associated with increased risk of in-utero HIV-1 transmission.

Objective: CCR5-tropic viruses are preferentially transmitted during perinatal HIV-1 infection. CCR5 density on CD4 + T-cells likely impacts susceptibility to HIV-1 infection.

Design: Fifty-two mother-infant dyads were enrolled.

Potential for Maternally Administered Vaccine for Infant Group B Streptococcus.

Background: Natural history studies have correlated serotype-specific anti-capsular polysaccharide (CPS) IgG in newborns with a reduced risk of group B streptococcal disease. A hexavalent CPS-cross-reactive material 197 glycoconjugate vaccine (GBS6) is being developed as a maternal vaccine to prevent invasive group B streptococcus in young infants.

Methods: In an ongoing phase 2, placebo-controlled trial involving pregnant women, we assessed the safety and immunogenicity of a single dose of various GBS6 formulations and analyzed maternally transferred anti-CPS antibodies.

Antepartum SARS-CoV-2 infection and adverse birth outcomes in South African women.

Background: SARS-CoV-2 infection in pregnant women has been associated with severe illness in the women and higher rates of premature delivery. There is, however, paucity of data on the impact of the timing of SARS-CoV-2 infection and on symptomatic or asymptomatic infections on birth outcomes. Data from low-middle income settings is also lacking.

Active Intrapartum SARS-CoV-2 Infection and Pregnancy Outcomes.

Objective: Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection during pregnancy has been associated with poor pregnancy outcomes. There is, however, not much information on the impact of the timing of SARS-CoV-2 infection on pregnancy outcomes, and studies from low-middle income settings are also scarce.

Study Design: We conducted a cross-sectional study from April to December 2020, in South Africa, to assess the association of SARS-CoV-2 infection on a nasal swab at the time of labor with fetal death, preterm birth, low birth weight, or pregnancy-induced complications.

FCGR3A gene duplication, FcγRIIb-232TT and FcγRIIIb-HNA1a associate with an increased risk of vertical acquisition of HIV-1.

Background: Some mother-to-child transmission (MTCT) studies suggest that allelic variations of Fc gamma receptors (FcγR) play a role in infant HIV-1 acquisition, but findings are inconsistent. To address the limitations of previous studies, the present study investigates the association between perinatal HIV-1 transmission and FcγR variability in three cohorts of South African infants born to women living with HIV-1.

Methods: This nested case-control study combines FCGR genotypic data from three perinatal cohorts at two hospitals in Johannesburg, South Africa.

Healthy dynamics of CD4 T cells may drive HIV resurgence in perinatally-infected infants on antiretroviral therapy.

In 2019 there were 490,000 children under five living with HIV. Understanding the dynamics of HIV suppression and rebound in this age group is crucial to optimizing treatment strategies and increasing the likelihood of infants achieving and sustaining viral suppression. Here we studied data from a cohort of 122 perinatally-infected infants who initiated antiretroviral treatment (ART) early after birth and were followed for up to four years.

Evaluation of submaximal endurance in young children living with HIV.

Background: There is growing concern about the long-term [a condition which is the consequence of a previous disease or injury] of perinatally acquired human immunodeficiency virus (HIV). Children living with HIV (CLHIV) present with cardiopulmonary impairments and decreased physical activity which may be due to poor endurance.

Objectives: Our study aimed to investigate the sub-maximal endurance of CLHIV compared to a non-infected comparison group.

Evaluating the performance of the GeneXpert HIV-1 qualitative assay as a consecutive test for a new early infant diagnosis algorithm in South Africa.

Background: The proportion of HIV-exposed infants and young children infected with HIV in South Africa (SA) has declined markedly over the past decade as a result of the country's comprehensive prevention of mother-to-child transmission programme. This decrease has in turn reduced the positive predictive value (PPV) of diagnostic assays, necessitating review of early infant diagnosis (EID) algorithms to ensure improved accuracy.

Objectives: To evaluate the performance of the GeneXpert HIV-1 qualitative assay (Xpert EID) as a consecutive test for infants with an 'HIV-detected' polymerase chain reaction screening test at birth.

Disclosure to South African children about their own HIV status over time.

Disclosure to children living with HIV (CLHIV) about their own status is associated with positive outcomes such as treatment adherence, but prior cross-sectional studies in sub-Saharan Africa report disclosure rates of <50%. This study aims to assess pediatric disclosure over time. 548 CLHIV were followed from 2/2013-4/2018 in Johannesburg, South Africa.

An HIV Vaccine Protective Allele in Associates With Increased Odds of Perinatal HIV Acquisition.

In the Thai RV144 HIV-1 vaccine trial, a three-variant haplotype within the Fc gamma receptor 2C gene () reduced the risk of HIV-1 acquisition. A follow-on trial, HVTN702, of a similar vaccine candidate found no efficacy in South Africa, where the predominant population is polymorphic for only a single variant in the haplotype, c.134-96C>T (rs114945036).

Predictors of Cell-Associated Human Immunodeficiency Virus (HIV)-1 DNA Over 1 Year in Very Early Treated Infants.

Background: Younger age of antiretroviral therapy (ART) initiation is associated with smaller viral reservoirs in perinatally acquired HIV-1 infection, but there is wide variability among early-treated infants. Predictors of this variability are not fully described.

Methods: Sixty-three neonates diagnosed with HIV-1 <48 hours after birth in Johannesburg, South Africa, were started on ART as soon as possible.

Persistently lower bone mass and bone turnover among South African children living with well controlled HIV.

Objective: We evaluated longitudinal trends and associations between bone mass, bone turnover and inflammatory markers among South African children living with HIV (CLHIV) and controls.

Design: We previously reported decreased bone mass among CLHIV independent of marked inflammation and increased bone turnover. The goal of this study was to evaluate longitudinal changes in bone mass, bone turnover and inflammation over 2 years.

Virologic Response to Very Early HIV Treatment in Neonates.

Factors that influence viral response when antiretroviral therapy (ART) is initiated in neonates are not well characterized. We assessed if there is consistency in predictive factors when operationalizing viral response using different methods. Data were collected from a clinical study in South Africa that started ART in neonates within 14 days of birth (2013-2018).

Normalization of B Cell Subsets but Not T Follicular Helper Phenotypes in Infants With Very Early Antiretroviral Treatment.

Infant HIV-1-infection is associated with high morbidity and mortality if antiretroviral treatment (ART) is not initiated promptly. We characterized development of circulating T follicular helper cells (cTfh) and their relationship to naïve/memory B cell subsets in a cohort of neonates initiating ART within the first week of life. Infants were diagnosed within 48 hours of birth and started ART as soon as possible.

Outcomes of newborn hearing screening at an academic secondary level hospital in Johannesburg, South Africa.

Background: The Health Professions Council of South Africa (HPCSA) issued early hearing detection and intervention guidelines, which has universal newborn hearing screening (UNHS) as one of the important goals. Despite established evidence of the importance of UNHS globally, there has been no mandated formalised and standardised implementation as yet in South Africa.

Objectives: The aim of this study was to describe the outcomes of newborn hearing screening (NHS) in an academic secondary level hospital in Johannesburg, South Africa.

Neurodevelopment in early treated HIV-infected infants participating in a developmental stimulation programme compared with controls.

Background: Neurodevelopmental stimulation programmes can improve developmental outcomes. Antiretroviral therapy (ART) started soon after birth potentially limits the invasion of HIV into the central nervous system. A combination of developmental stimulation and early ART initiation may reduce developmental delays in children with perinatally acquired HIV infection.

Low Pretreatment Viral Loads in Infants With HIV in an Era of High-maternal Antiretroviral Therapy Coverage.

Background: With expansion of antiretroviral therapy (ART) programs, transmission rates are low but new infant infections still occur. We investigated predictors of pre-ART viral load (VL) and CD4+ T-cell counts and percentages in infants diagnosed with HIV at birth in a setting with high coverage of maternal ART and infant prophylaxis.

Methods: As part of an early treatment study, 97 infants with confirmed HIV-infection were identified at a hospital in Johannesburg, South Africa.

Switch to Efavirenz Attenuates Lipoatrophy in Girls With Perinatal HIV.

Objectives: Children with HIV (CHIV) have lifetime exposure to antiretrovirals (ART); therefore, optimizing their regimens to have the least impact on fat redistribution is a priority.

Methods: This is a cross-sectional study of 219 perinatally infected CHIV and 219 HIV-uninfected controls from similar socioeconomic backgrounds in Johannesburg, South Africa. We compared total body and regional fat distribution in CHIV on suppressive ART regimens with controls and, among CHIV, between ritonavir-boosted lopinavir (LPV/r)-based and efavirenz (EFV)-based regimens.

Behavioral Functioning and Quality of Life in South African Children Living with HIV on Antiretroviral Therapy.

This study examined behavioral functioning and quality of life in South African children living with perinatally acquired HIV. Compared with controls, children living with perinatally acquired HIV had a higher mean total difficulties score assessed by the Strengths and Difficulties Questionnaire and lower mean quality of life scores assessed by the Pediatric Quality of Life Inventory.