Socioemotional and behavioural difficulties in children with chronic physical conditions: analysis of the Longitudinal Study of Australian Children.

Objectives: To examine the prevalence of socioemotional and behavioural difficulties (SEBDs) in children with chronic physical conditions (CPCs) and to analyse how this prevalence varied with the type and number of CPCs and the age of the child.

Design: Cross-sectional study of a secondary data analysis of the Longitudinal Study of Australian Children.

Setting: An Australian nationally representative sample of general population of children.

Pharmacokinetics and Safety of a Raltegravir-Containing Regimen in Children Aged 4 Weeks to 2 Years Living With Human Immunodeficiency Virus and Receiving Rifampin for Tuberculosis.

Unlabelled: Pharmacological interactions limit treatment options for children living with human immunodeficiency virus (HIV) and tuberculosis (TB). We found that 12 mg/kg twice daily raltegravir chewable tablets (administered after crushing) safely achieved pharmacokinetic targets in children living with HIV aged 4 weeks to <2 years receiving concurrent rifampin to treat TB.

Clinical Trials Registration: NCT01751568.

Pharmacokinetics and safety of a raltegravir-containing regimen in HIV-infected children aged 2-12 years on rifampicin for tuberculosis.

Objectives: Drug-drug interactions limit current antiretroviral treatment options for HIV-infected children with tuberculosis (TB). Rifampicin (RIF) induces UDP-glucuronosyltransferase activity, accelerating the clearance of raltegravir (RAL). We sought to establish an optimal and well tolerated dose of RAL when administered with RIF to HIV and TB co-infected children.

Hepatitis B virus infection in children and adolescents.

Hepatitis B virus (HBV) infection is a major cause of acute and chronic liver disease and associated morbidity and mortality worldwide. Vertical (mother-to-child) and horizontal early childhood transmission are the main routes of HBV transmission and are responsible for most chronic infections, including among adults who bear the greatest burden of morbidity and mortality. Universal hepatitis B immunisation at birth and in infancy is the key strategy for global elimination of HBV infection, and has been highly effective in reducing new vertical infections.

Hepatitis C virus infection in children and adolescents.

Hepatitis C virus (HCV) infection is a major cause of chronic liver disease and associated morbidity and mortality worldwide. Short-course, oral, curative, direct-acting antiviral regimens have transformed treatment for HCV infection. Since the 2016 launch of the first global strategy towards elimination of viral hepatitis as a public health threat by 2030, the predominant focus of the global response has been on the treatment of adults, who bear the greatest burden of morbidity and mortality of HCV-related chronic liver disease.

Virologic failure among children taking lopinavir/ritonavir-containing first-line antiretroviral therapy in South Africa.

Objective: To report the outcomes, clinical management decisions and results of resistance testing among a group of children who developed virologic failure on first-line lopinavir/ritonavir (LPV/r)-based therapy from a large cohort of antiretroviral therapy-treated children in Soweto.

Design: Historical cohort study.

Methods: Children with virologic failure were identified from a group of 1692 children <3 years who had initiated first-line LPV/r-containing therapy since 2000 up to the end November 2011.

Age-specific and sex-specific weight gain norms to monitor antiretroviral therapy in children in low-income and middle-income countries.

Background: Viral load and CD4% are often not available in resource-limited settings for monitoring children's responses to antiretroviral therapy (ART). We aimed to construct normative curves for weight gain at 6, 12, 18, and 24 months following initiation of ART in children, and to assess the association between poor weight gain and subsequent responses to ART.

Design: Analysis of data from HIV-infected children younger than 10 years old from African and Asian clinics participating in the International epidemiologic Databases to Evaluate AIDS.

Positive association between dietary iron intake and iron status in HIV-infected children in Johannesburg, South Africa.

Anemia is a common complication of pediatric HIV infection and is associated with suboptimal cognitive performance and growth failure. Routine iron supplementation is not provided to South African HIV-infected children. We hypothesized that dietary iron intake without supplementation is sufficient to protect against iron deficiency (ID) in HIV-infected children receiving highly active antiretroviral therapy.

Frequency of stavudine substitution due to toxicity in children receiving antiretroviral treatment in sub-Saharan Africa.

Introduction: Stavudine is a commonly used drug in paediatric antiretroviral treatment (ART) regimens. Due to toxicity concerns, however, the drug abacavir has replaced stavudine in first-line paediatric regimens in many countries. We describe the frequency of stavudine toxicity in children receiving ART at a treatment clinic in Soweto, South Africa.

Effect of baseline immune suppression on growth recovery in HIV positive South African children receiving antiretroviral treatment.

Background: Growth failure is common among children infected with HIV. The degree of growth recovery and its determinants in children initiating combination antiretroviral therapy (cART) are not well understood.

Methods: We conducted a cohort study of children who initiated cART between 2004 and 2008 at a pediatric HIV clinic in Johannesburg, South Africa.

Changes in pediatric HIV-related hospital admissions and mortality in Soweto, South Africa, 1996-2011: light at the end of the tunnel?

Background: With widespread availability of pediatric antiretroviral therapy and improved access to prevention of mother-to-child transmission (PMTCT), it is important to monitor the impact on pediatric HIV-related hospital admissions and in-hospital mortality in South Africa.

Methods: Over a 15-year period, 4 independent surveillance studies were conducted in the pediatric wards at Chris Hani Baragwanath Hospital in Soweto, South Africa (1996, 2005, 2007, and late 2010 to early 2011). Trends in HIV prevalence and HIV-related mortality were evaluated.

Switching children previously exposed to nevirapine to nevirapine-based treatment after initial suppression with a protease-inhibitor-based regimen: long-term follow-up of a randomised, open-label trial.

Background: Protease-inhibitor-based treatment is recommended as first-line for infants infected with HIV who have been previously exposed to nevirapine prophylaxis. However, long-term use poses adherence challenges, is associated with metabolic toxic effects, restricts second-line options, and is costly. We present the long-term outcomes of switching nevirapine-exposed children to nevirapine-based treatment after effective suppression of virus replication with a protease-inhibitor-based regimen.

Neurodevelopmental delay among HIV-infected preschool children receiving antiretroviral therapy and healthy preschool children in Soweto, South Africa.

Neurodevelopmental delay has been documented in up to 97.5% of HIV-infected children in Soweto who were not yet on antiretroviral treatment (ART). With growing numbers of children in South Africa being successfully treated with ART, the effects of ART on neurocognitive functioning in children require investigation.

Lipid profiles in young HIV-infected children initiating and changing antiretroviral therapy.

Background: Both HIV infection and antiretroviral therapy are associated with dyslipidemias in adults, but there are fewer data on outcomes in young children. Here we examined lipid profile changes in a cohort of young children before and after suppression on an initial ritonavir-boosted lopinavir (LPV/r)-based regimen and after switch to a nevirapine (NVP)-based regimen.

Methods: One hundred ninety-five HIV-infected children who initiated LPV/r-based therapy when <24 months of age at 1 site in Johannesburg, South Africa, and who achieved viral suppression (<400 copies/mL sustained for ≥ 3 months) were randomized to either continue on the LPV/r-based regimen (n = 99) or to switch to a NVP-based regimen (n = 96).

Antiretroviral therapy for children in resource-limited settings: current regimens and the role of newer agents.

WHO antiretroviral treatment guidelines for HIV-infected children have influenced the design of treatment programmes in resource-limited settings. This review analyses the latest WHO first- and second-line regimen recommendations. The recommendation to use lopinavir/ritonavir-containing first-line regimens in young children with prior non-nucleoside reverse transcriptase inhibitor (NNRTI) exposure is based on good quality evidence.

Antiretroviral therapy responses among children attending a large public clinic in Soweto, South Africa.

Background: Antiretroviral therapy (ART) access with successful outcomes for children is expanding in resource-limited countries. The aim of this study was to determine treatment responses of children in a routine setting where first-line therapy with lopinavir/ritonavir is routinely included for young children.

Methods: Outpatient records of children who initiated ART between April 2004 and March 2008 at a government clinic in Soweto were reviewed.

HIV-1 drug resistance at antiretroviral treatment initiation in children previously exposed to single-dose nevirapine.

Objective: To describe the prevalence of HIV-1 drug resistance mutations at the time of treatment initiation in a large cohort of HIV-infected children previously exposed to single-dose nevirapine (sdNVP) for prevention of transmission.

Design: Drug resistance mutations were measured pretreatment in 255 infants and young children under 2 years of age in South Africa exposed to sdNVP and initiating ritonavir-boosted lopinavir-based therapy. Those who achieved viral suppression were randomized to either continue the primary regimen or to switch to a nevirapine-based regimen.

Lopinavir exposure is insufficient in children given double doses of lopinavir/ritonavir during rifampicin-based treatment for tuberculosis.

Background: Coadministration of rifampicin dramatically reduces the concentrations of protease inhibitors. A pharmacokinetic study in healthy adults showed that doubling the dose of coformulated lopinavir/ritonavir was able to overcome the inducing effect of rifampicin. We evaluated this strategy in children treated with rifampicin-based antituberculosis therapy attending antiretroviral clinics in South Africa.

Antiretroviral therapy outcomes in HIV-infected children after adjusting protease inhibitor dosing during tuberculosis treatment.

Background: Modification of ritonavir-boosted lopinavir (LPV/r)-based antiretroviral therapy is required for HIV-infected children co-treated for tuberculosis (TB). We aimed to determine virologic and toxicity outcomes among TB/HIV co-treated children with the following modifications to their antiretroviral therapy (ART): (1) super-boosted LPV/r, (2) double-dose LPV/r or (3) ritonavir.

Methods And Findings: A medical record review was conducted at two clinical sites in Johannesburg, South Africa.

Rapid development of antiretroviral drug resistance mutations in HIV-infected children less than two years of age initiating protease inhibitor-based therapy in South Africa.

Data on the development of antiretroviral drug resistance in HIV-1-infected children receiving protease inhibitor (PI)-based antiretroviral therapy (ART) are limited. We examined antiretroviral resistance among a cohort of 323 South African HIV-infected children <2 years old exposed to nevirapine for prevention of mother-to-child transmission. Ritonavir (RTV) was used initially for 138 children who were <6 months old or receiving antimycobacterial therapy; otherwise children received lopinavir/ritonavir (LPV/r)-based ART.

Induction therapy with protease-inhibitors modifies the effect of nevirapine resistance on virologic response to nevirapine-based HAART in children.

Background: Nevirapine resistance after failed prophylaxis to prevent mother-to-child human immunodeficiency virus (HIV) transmission can compromise subsequent nevirapine-based highly active antiretroviral therapy (HAART).

Methods: Nevirapine-exposed children who achieved virologic suppression with lopinavir/ritonavir-based induction HAART before switch to nevirapine-based HAART or who continued the lopinavir/ritonavir regimen were studied. Nevirapine-resistant HIV was quantified (≥ 1% frequency) in plasma before therapy and archived in peripheral blood mononuclear cells after induction HAART with ultradeep pyrosequencing.

Antiretroviral treatment for children with peripartum nevirapine exposure.

Background: Single-dose nevirapine is the cornerstone of the regimen for prevention of mother-to-child transmission of human immunodeficiency virus (HIV) in resource-limited settings, but nevirapine frequently selects for resistant virus in mothers and children who become infected despite prophylaxis. The optimal antiretroviral treatment strategy for children who have had prior exposure to single-dose nevirapine is unknown.

Methods: We conducted a randomized trial of initial therapy with zidovudine and lamivudine plus either nevirapine or ritonavir-boosted lopinavir in HIV-infected children 6 to 36 months of age, in six African countries, who qualified for treatment according to World Health Organization (WHO) criteria.

Extreme genetic divergence is required for coreceptor switching in HIV-1 subtype C.

Background: Coreceptor switching from CCR5 to CXCR4 is less common in subtype C HIV-1 infection than in subtype B for reasons that are unclear. We have examined sequential virus samples from a subtype C-infected child who had evidence of coreceptor switching.

Methods: To examine HIV-1 envelope evolution towards CXCR4 usage, env sequences were correlated with phenotypic characteristics determined by entry assays, as well as the ability to use alternative coreceptors such as FPRL1, CCR3, CCR8 and others.

Reuse of nevirapine in exposed HIV-infected children after protease inhibitor-based viral suppression: a randomized controlled trial.

Context: Protease inhibitor (PI)-based therapy is recommended for infants infected with human immunodeficiency virus (HIV) who were exposed to nevirapine for prevention of mother-to-child HIV transmission. However, there are limitations of continuing PI-based therapy indefinitely and reuse of nevirapine has many advantages.

Objective: To test whether nevirapine-exposed infants who initially achieve viral suppression with PI-based therapy can maintain viral suppression when switched to nevirapine-based therapy.