Similar cortical morphometry trajectories from 5 to 9 years in children with perinatal HIV who started treatment before age 2 years and uninfected controls.

Background: Life-long early ART (started before age 2 years), often with periods of treatment interruption, is now the standard of care in pediatric HIV infection. Although cross-sectional studies have investigated HIV-related differences in cortical morphology in the setting of early ART and ART interruption, the long-term impact on cortical developmental trajectories is unclear. This study compares the longitudinal trajectories of cortical thickness and folding (gyrification) from age 5 to 9 years in a subset of children perinatally infected with HIV (CPHIV) from the Children with HIV Early antiRetroviral therapy (CHER) trial to age-matched children without HIV infection.

Machine learning outperformed logistic regression classification even with limit sample size: A model to predict pediatric HIV mortality and clinical progression to AIDS.

Logistic regression (LR) is the most common prediction model in medicine. In recent years, supervised machine learning (ML) methods have gained popularity. However, there are many concerns about ML utility for small sample sizes.

Pharmacokinetics, safety, tolerability, and antiviral activity of dolutegravir dispersible tablets in infants and children with HIV-1 (IMPAACT P1093): results of an open-label, phase 1-2 trial.

Background: Safe and potent antiretroviral medications in child-friendly formulations are needed to treat young children living with HIV-1. We aimed to select dosing for a dispersible tablet formulation of dolutegravir that achieved pharmacokinetic exposures similar to those in adults, and was safe and well tolerated in young children.

Methods: International Maternal Pediatric Adolescent AIDS Clinical Trial (IMPAACT) P1093 is a phase 1-2 ongoing multicentre, open-label, non-comparative study of dolutegravir.

Cortical structural changes related to early antiretroviral therapy (ART) interruption in perinatally HIV-infected children at 5 years of age.

ART interruption in children can occur especially in resource-limited settings for reasons including poor adherence, stock-outs, ART intolerance of non-pediatric formulas and pill size, as well as ultimately to test for HIV remission. Although early ART initiation is now standard of care in pediatric HIV management, very little is known on the effect of early ART initiation or subsequent interruption on brain development. This study aimed to investigate the effect of ART interruption on brain cortical thickness (CT) and folding in a subset of children from the Children with HIV Early antiRetroviral therapy (CHER) trial cohort who all started ART before 18 months of age.

MRS suggests multi-regional inflammation and white matter axonal damage at 11 years following perinatal HIV infection.

The neurological changes in children living with perinatal HIV (PHIV) on antiretroviral therapy (ART) can be studied at a metabolic level through proton magnetic resonance spectroscopy. While previous studies in children have largely focused on individual metabolite changes, investigating patterns within and across regions of interest can aid in identifying metabolic markers of HIV infection. In this study 76 children with PHIV from the Children with HIV Early AntiRetroviral (CHER) trial, 30 children who were HIV-exposed-uninfected (HEU) and 30 children who were HIV-unexposed (HU), were scanned at the age of 11.

Recovery of HIV encephalopathy in perinatally infected children on antiretroviral therapy.

Aim: To describe the trajectory of clinical signs in children who developed human immunodeficiency virus encephalopathy (HIVE) after starting early antiretroviral therapy (ART).

Method: This was a retrospective case-cohort description of HIVE among Cape Town participants from the Children with HIV Early AntiRetroviral treatment (CHER) trial. Criteria for HIVE diagnosis were at least two of: (1) acquired central motor deficit, (2) impaired brain growth, and (3) failure to attain or loss of developmental milestones in the absence of an alternative aetiology.

Perinatal HIV Infection or Exposure Is Associated With Low -Acetylaspartate and Glutamate in Basal Ganglia at Age 9 but Not 7 Years.

Abnormalities of the basal ganglia are frequently seen in HIV-infected (HIV+) children despite antiretroviral treatment (ART) initiation during childhood. Assessment of metabolites associated with neuronal integrity or with glial proliferation can present a sensitive description of metabolic events underlying basal ganglia structural changes. We used magnetic resonance spectroscopy to examine differences in creatine, choline, -acetylaspartate (NAA), glutamate, and myo-inositol between HIV+ children and HIV-unexposed controls, as well as between HIV-exposed uninfected (HEU) children and HIV-unexposed controls at age 7 and at age 9.

Five year neurodevelopment outcomes of perinatally HIV-infected children on early limited or deferred continuous antiretroviral therapy.

Introduction: Early antiretroviral therapy (ART) has improved neurodevelopmental outcomes of HIV-infected (HIV-positive) children; however, little is known about the longer term outcomes in infants commencing early ART or whether temporary ART interruption might have long-term consequences. In the children with HIV early antiretroviral treatment (CHER) trial, HIV-infected infants ≤12 weeks of age with CD4 ≥25% were randomized to deferred ART (ART-Def); immediate time-limited ART for 40 weeks (ART-40W) or 96 weeks (ART-96W). ART was restarted in the time-limited arms for immunologic/clinical progression.

Favourable outcome in a child with symptomatic diagnosis of Glutaric aciduria type 1 despite vertical HIV infection and minor head trauma.

The first case of Glutaric aciduria Type 1(GA1) in an African child was reported in 2001. GA1 has a prevalence of 1:5000 in black South Africans. Although early diagnosis is essential for a favourable outcome, newborn screening is not routine in South Africa where an estimated 320,000 children have HIV infection.

Functional Connectivity Alterations between Networks and Associations with Infant Immune Health within Networks in HIV Infected Children on Early Treatment: A Study at 7 Years.

Although HIV has been shown to impact brain connectivity in adults and youth, it is not yet known to what extent long-term early antiretroviral therapy (ART) may alter these effects, especially during rapid brain development in early childhood. Using both independent component analysis (ICA) and seed-based correlation analysis (SCA), we examine the effects of HIV infection in conjunction with early ART on resting state functional connectivity (FC) in 7 year old children. HIV infected (HIV+) children were from the Children with HIV Early Antiretroviral Therapy (CHER) trial and all initiated ART before 18 months; uninfected children were recruited from an interlinking vaccine trial.

Altered brain morphometry in 7-year old HIV-infected children on early ART.

Even with the increased roll out of combination antiretroviral therapy (cART), paediatric HIV infection is associated with neurodevelopmental delays and neurocognitive deficits that may be accompanied by alterations in brain structure. Few neuroimaging studies have been done in children initiating ART before 2 years of age, and even fewer in children within the critical stage of brain development between 5 and 11 years. We hypothesized that early ART would limit HIV-related brain morphometric deficits at age 7.

Late-Onset Hiv Encephalopathy In Children With Long-Standing Virologic Suppression Followed By Slow Spontaneous Recovery Despite no Change In Antiretroviral Therapy: 4 Case Reports.

We describe 4 Children with HIV Early Antiretroviral Therapy trial participants with late-onset HIV encephalopathy despite long-standing viral suppression in blood and undetectable HIV DNA and RNA polymerase chain reaction in cerebrospinal fluid. Extensive investigations revealed no alternative etiology. Reassuringly, all 4 experienced slow spontaneous recovery despite no change in antiretroviral therapy.

HIV-associated CD4+/CD8+ depletion in infancy is associated with neurometabolic reductions in the basal ganglia at age 5 years despite early antiretroviral therapy.

Objective: Investigating consequences of early or late antiretroviral therapy (ART) initiation in infancy on young brain development using magnetic resonance spectroscopy.

Design: Most pediatric HIV/ART-related neurological studies are from neuropsychological/clinical perspectives. Magnetic resonance spectroscopy can elucidate the mechanisms underpinning neurocognitive outcomes by quantifying the brain's chemical condition through localized metabolism to provide insights into health and development.

Single Genome Analysis for the Detection of Linked Multiclass Drug Resistance Mutations in HIV-1-Infected Children After Failure of Protease Inhibitor-Based First-Line Therapy.

The WHO recommends protease inhibitor (PI)-based antiretroviral therapy (ART) for vertically infected children after failed nevirapine (NVP) prophylaxis. Emergence of PI resistance on the backdrop of preexisting non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance could compromise long-term treatment options in such children. We characterized multiclass drug resistance using single genome sequencing (SGS) in children with viremia while receiving PI-based ART.

White matter signal abnormalities in children with suspected HIV-related neurologic disease on early combination antiretroviral therapy.

Background: The natural history and manifestation of HIV-related neurologic disease have been ameliorated by combination antiretroviral therapy (ART). We describe the characteristics of white matter signal abnormalities (WMSA) on magnetic resonance imaging in children with HIV-related neurologic disease.

Methods: We reviewed magnetic resonance imaging scans of children with suspected HIV-related neurologic disease despite early ART and correlated with clinical, neurodevelopmental data, virologic markers and time on ART.

Early time-limited antiretroviral therapy versus deferred therapy in South African infants infected with HIV: results from the children with HIV early antiretroviral (CHER) randomised trial.

Background: Interim results from the children with HIV early antiretroviral (CHER) trial showed that early antiretroviral therapy (ART) was life-saving for infants infected with HIV. In view of the few treatment options and the potential toxicity associated with lifelong ART, in the CHER trial we compared early time-limited ART with deferred ART.

Methods: CHER was an open-label randomised controlled trial of HIV-infected asymptomatic infants younger than 12 weeks in two South African trial sites with a percentage of CD4-positive T lymphocytes (CD4%) of 25% or higher.

Immunogenicity following the first and second doses of 7-valent pneumococcal conjugate vaccine in HIV-infected and -uninfected infants.

Background: The immunogenicity of pneumococcal conjugate vaccine (PCV) has not been evaluated in HIV-infected infants following the first and second PCV-doses. We studied antibody kinetics of serotypes included in 7-valent PCV in HIV-infected and HIV-uninfected infants prior to and following each of three PCV-doses.

Methods: HIV-uninfected infants born to HIV-uninfected (HUU) and HIV-infected mothers (HEU); and perinatal HIV-infected children with CD(4+)<25% randomized to initiate antiretroviral treatment (ART) when clinically and/or immunologically indicated (ART-) or immediately (ART+) were enrolled.

Early antiretroviral therapy improves neurodevelopmental outcomes in infants.

Objectives: To evaluate the effect of early versus deferred antiretroviral therapy (ART) on the neurodevelopment of infants from Cape Town participating in the Children with HIV Early Antiretroviral Therapy (CHER) trial.

Design: HIV-infected infants were randomized to early (<3 months) or deferred ART. HIV-uninfected infants (HIV-exposed and HIV-unexposed) provide background data.

Utility of clinical parameters to identify HIV infection in infants below ten weeks of age in South Africa: a prospective cohort study.

Background: As HIV-infected infants have high mortality, the World Health Organization now recommends initiating antiretroviral therapy as early as possible in the first year of life. However, in many settings, laboratory diagnosis of HIV in infants is not readily available. We aimed to develop a clinical algorithm for HIV presumptive diagnosis in infants < 10 weeks old using screening data from the Children with HIV Early Antiretroviral therapy (CHER) study in South Africa.

Early Antiretroviral Therapy reduces the incidence of otorrhea in a randomized study of early and deferred antiretroviral therapy: Evidence from the Children with HIV Early Antiretroviral Therapy (CHER) Study.

Background: Although otorrhea occurs commonly in HIV-infected infants, there are few data. We compared the incidence of otorrhea in infants receiving early vs deferred ART in the Children with HIV Early Antiretroviral (CHER) trial. Infants aged 6 to 12 weeks of age with confirmed HIV infection and a CD4 percentage greater than or equal to 25% were randomized to early or deferred ART at two sites in South Africa.