Long-Term Changes of Subcutaneous Fat Mass in HIV-Infected Children on Antiretroviral Therapy: A Retrospective Analysis of Longitudinal Data from Two Pediatric HIV-Cohorts.

Objective: Longitudinal studies objectively evaluating changes in regional fat distribution of HIV-infected children assessed by whole body dual energy X-ray absorptiometry (DEXA) are scarce, whilst this long-term effect of HIV and antiretroviral therapy (cART) is an important issue in infected children in need for lifelong treatment.

Methods: We assessed regional fat distribution over time, measured with sequential DEXA-scans in HIV-infected children on cART in cohorts from South Africa (SA) and the Netherlands (NL), and in healthy controls (SA). Limb and trunk fat Z-scores were calculated with the lambda-mu-sigma (LMS) method.

Country of birth does not influence long-term clinical, virologic, and immunological outcome of HIV-infected children living in the Netherlands: a cohort study comparing children born in the Netherlands with children born in Sub-Saharan Africa.

Background: Immigrant HIV-infected adults in industrialized countries show a poorer clinical and virologic outcome compared with native patients. We aimed to investigate potential differences in clinical, immunological, and virologic outcome in Dutch HIV-infected children born in the Netherlands (NL) versus born in Sub-Saharan Africa (SSA) in a national cohort analysis.

Methods: We included all HIV-infected children registered between 1996 and 2013.

Safety and effectiveness of combination antiretroviral therapy during the first year of treatment in HIV-1 infected Rwandan children: a prospective study.

Background: With increased availability of paediatric combination antiretroviral therapy (cART) in resource limited settings, cART outcomes and factors associated with outcomes should be assessed.

Methods: HIV-infected children <15 years of age, initiating cART in Kigali, Rwanda, were followed for 18 months. Prospective clinical and laboratory assessments included weight-for-age (WAZ) and height-for-age (HAZ) z-scores, complete blood cell count, liver transaminases, creatinine and lipid profiles, CD4 T-cell count/percent, and plasma HIV-1 RNA concentration.

"Let's talk about sex": a qualitative study of Rwandan adolescents' views on sex and HIV.

Objective: This qualitative study explored the views and experiences of adolescents with perinatally acquired HIV in Kigali, Rwanda, regarding sex, love, marriage, children and hope for the future.

Design: The study enrolled 42 adolescents who had received combination antiretroviral therapy for at least 12 months, and a selection of their primary caregivers. Study methods included 3 multiple day workshops consisting of role-playing and focus group discussions (FGDs) with adolescents, 8 in-depth interviews with adolescents, and one FGD with caregivers.

Long-term effectiveness of combination antiretroviral therapy and prevalence of HIV drug resistance in HIV-1-infected children and adolescents in Rwanda.

Objective: To determine the long-term outcomes of treatment and prevalence of genotypic drug resistance in children and adolescents on combination antiretroviral therapy.

Methods: A cross-sectional study (September 2009 to October 2010) in which clinical, immunologic and virologic outcomes were assessed at a single-study visit and through patient records in a cohort of HIV-infected children and adolescents. Risk factors for clinical and immunologic responses and virologic outcome were evaluated using logistic regression, and the accuracy of clinical and immunologic criteria in identifying virologic failure was assessed.

Long-term response to combination antiretroviral therapy in HIV-infected children in the Netherlands registered from 1996 to 2012.

Objectives: To describe demographic and treatment characteristics of the Dutch vertically HIV-infected paediatric population from 1996 to 2012, and to investigate the long-term virological and immunological response to combination antiretroviral therapy (cART), with emphasis on the influence of age at cART initiation and initial CD4 cell counts.

Design: Descriptive cohort study.

Methods: From 1996 to 2012, all paediatric HIV clinics in the Netherlands provided data on their HIV-infected population.

Sustained virological response on second-line antiretroviral therapy following virological failure in HIV-infected patients in rural South Africa.

Objective: This study aims to describe the virological, immunological and clinical efficacy of protease inhibitor (PI)-based second-line antiretroviral therapy (ART) in rural South Africa.

Methods: An observational cohort study was performed on 210 patients (including 39 children) who initiated PI-based second-line therapy at least 12 months prior to data collection. Biannual clinical, immunological and virological monitoring was performed.

Hepatitis B virus prevalence and vaccine response in HIV-infected children and adolescents on combination antiretroviral therapy in Kigali, Rwanda.

Objective: The aim of this study was to determine the prevalence of hepatitis B virus (HBV) infection in a cohort of HIV-infected Rwandan children and adolescents on combination antiretroviral therapy (cART), and the success rate of HBV vaccination in those children found to be HBV negative.

Methods: HIV-infected children and adolescents (age 8-17 years) receiving cART with CD4 T-cells count ≥200 cells/mm and/or ≥15% and without prior HBV vaccination (by history, vaccination cards and clinic records) underwent serologic testing for past (negative HBV surface antigen [HBsAg] with positive antibody to HBV core antigen [cAb] and to HBsAg [anti-HBs]) or active HBV infection (positive HBsAg). Children with any positive HBV serologic tests were excluded from further vaccination; all others completed 3 HBV immunizations with 10 µg of ENGERIX-B.

Mid-dosing interval efavirenz plasma concentrations in HIV-1-infected children in Rwanda: treatment efficacy, tolerability, adherence, and the influence of CYP2B6 polymorphisms.

This study evaluated mid-dosing interval efavirenz plasma concentrations and the influence of CYP2B6 polymorphisms in relation to efficacy, tolerability, and adherence in 97 Rwandan HIV-infected children (3-16 years). Plasma drug concentrations and CYP2B6 polymorphisms were determined. Ten children were excluded for nonadherence.

Barriers to Initiation of Pediatric HIV Treatment in Uganda: A Mixed-Method Study.

Although the advantages of early infant HIV diagnosis and treatment initiation are well established, children often present late to HIV programs in resource-limited settings. We aimed to assess factors related to the timing of treatment initiation among HIV-infected children attending three clinical sites in Uganda. Clinical and demographic determinants associated with early disease (WHO clinical stages 1-2) or late disease (stages 3-4) stage at presentation were assessed using multilevel logistic regression.

Accumulation of drug resistance and loss of therapeutic options precede commonly used criteria for treatment failure in HIV-1 subtype-C-infected patients.

Background: Virological monitoring is essential to identify antiretroviral treatment (ART) failure, but not widely available. Here, accumulation of resistance and consequences for second-line therapy were investigated in African HIV-1 subtype-C-infected patients.

Methods: A total of 836 patients initiated non-nucleoside reverse transcriptase inhibitor (NNRTI)-based ART and received biannual HIV RNA monitoring.

HIV-1-resistance-associated mutations after failure of first-line antiretroviral treatment among children in resource-poor regions: a systematic review.

HIV-positive children are at high risk of drug resistance, which is of particular concern in settings where antiretroviral options are limited. In this Review we explore resistance rates and patterns among children in developing countries in whom antiretroviral treatment has failed. We did a systematic search of online databases and conference abstracts and included studies reporting HIV-1 drug resistance after failure of first-line paediatric regimens in children (<18 years) in resource-poor regions (Latin America, Africa, and Asia).

Long-term outcome of children receiving antiretroviral treatment in rural South Africa: substantial virologic failure on first-line treatment.

Background: Long-term (>12 months follow-up) virologic data of children receiving antiretroviral therapy (ART) in Sub-Saharan Africa are limited. Data from rural areas are especially scarce. The aim of this study was to evaluate the long-term virologic outcome of a pediatric cohort in rural South Africa.

Improved general health of international adoptees, but immunization status still insufficient.

We studied the demographic and clinical data from 495 adopted children seen between January 2002 and January 2007 to evaluate the medical condition and immunization status of international adoptees. The data of children from Chinese origin (53.5%) were compared to children arriving from other countries.

Restoration of the CD4 T cell compartment after long-term highly active antiretroviral therapy without phenotypical signs of accelerated immunological aging.

It remains uncertain whether full T cell reconstitution can be established in HIV-infected children and adults with long-term sustained virological control by highly active antiretroviral therapy (HAART). In this study, we comprehensively analyzed various phenotypical markers of CD4 T cell recovery. In addition to measuring T cell activation and proliferation markers, CD4 T cell generation and aging of the CD4 T cell compartment were assessed by measuring TCR excision circles and the fraction of CD31-expressing naive CD4 T cells.

Neurocognitive function profile in HIV-infected school-age children.

Objectives: Evaluation of neurocognitive function of school-age children with HIV.

Design: Cross-sectional observational study.

Methods: Twenty-two children (median age 9.

Plasma vascular endothelial growth factor in severe sepsis.

Vascular endothelial growth factor (VEGF) is a potent vascular permeability factor. The development of capillary leak is common in septic patients, and several sepsis-associated mediators may induce VEGF production. The potential role of VEGF during sepsis has not been studied to date.

Vascular endothelial growth factor and blood-brain barrier disruption in tuberculous meningitis.

Background: Tuberculous meningitis (TBM) is characterized by disruption of the blood-brain barrier (BBB), cerebral edema and increased intracranial pressure (ICP). Vascular endothelial growth factor (VEGF) is a potent vascular permeability factor and a mediator of brain edema.

Aims: To investigate whether in children with TBM disruption of the BBB relates to VEGF production and to assess the effect of corticosteroids on Mycobacterium tuberculosis-induced VEGF production by mononuclear leukocytes.

Pharmacokinetics of nelfinavir in children: influencing factors and dose implications.

Objectives: The study describes the pharmacokinetics (PK) of the protease inhibitor nelfinavir and its active metabolite M8 in children and evaluates the influence of patient-related factors on nelfinavir plasma levels.

Methods: HIV-1-infected children treated with nelfinavir every 8 h (q8h) were eligible for inclusion in this retrospective study. 0-8 h intensive plasma pharmacokinetics (PK) sampling was performed at steady state.

Ritonavir-enhanced pharmacokinetics of nelfinavir/M8 during rifampin use.

Objective: To describe a case of successful protease inhibitor-based highly active antiretroviral therapy (HAART) concomitant with rifampin.

Case Summary: In a 7-month-old male infant with tuberculosis and HIV-1 infection, tuberculosis therapy including rifampin and HAART containing the protease inhibitor nelfinavir 40 mg/kg every 8 hours was started. Intensive steady-state pharmacokinetic sampling from baseline to 8 hours revealed very low plasma concentrations of nelfinavir: area under the plasma concentration-time curve (AUC(0-24)) <10% of adult population values for 750 mg every 8 hours and nonquantifiable concentrations of nelfinavir's principal metabolite (M8).

Endocrinologic and immunologic factors associated with recovery of growth in children with human immunodeficiency virus type 1 infection treated with protease inhibitors.

Introduction: Growth failure is a common presenting sign in children with HIV disease and is a sensitive indicator of disease progression in children with AIDS. Highly active antiretroviral therapy (HAART) is associated with a significant decrease in viral load and a subsequent rise in CD4+ T cell counts in HIV-1-infected children and also with increased height and weight. The underlying mechanisms of catch-up growth during HAART are yet unknown.

Results of 2 years of treatment with protease-inhibitor--containing antiretroviral therapy in dutch children infected with human immunodeficiency virus type 1.

Clinical, virologic, and immunologic responses to treatment that contained either indinavir or nelfinavir (both regimens included zidovudine and lamivudine) were determined in 32 children infected with human immunodeficiency virus type 1 (HIV-1) who participated for >/= 96 weeks in a prospective, open, uncontrolled multicenter trial. The pharmacokinetics of indinavir and of nelfinavir were determined and showed large interindividual differences. After 96 weeks of therapy, 69% and 50% of the patients had an HIV-1 RNA load that was below the HIV assays' detection limits of 500 and 40 copies/mL, respectively.