Antiretroviral therapy (ART) has greatly improved the survival of HIV-infected children. However, ART is associated with immediate and long-term adverse events. Pharmacovigilance systems, although imperfect, have been developed in many high-income countries (HICs), but coverage in low- and middle-income countries (LMICs) is poor and uneven. This review covers the recent advances in the understanding of adverse events following perinatal ART exposure, including surveillance from birth cohorts; we also describe the adverse events of antiretroviral drugs among HIV-infected children, focussing particularly on those relevant to LMICs, where more than 90% of HIV-infected children live.
ART is largely safe in both HIV-infected and HIV-exposed uninfected children, in whom no significant increase in birth defects has been noted. Among HIV-infected children, toxicity to some drugs may be less frequent than in adults, possibly related to immature immune systems in younger children. As per WHO guidelines, many countries are moving from stavudine-based to zidovudine-based or abacavir-based fixed-dose combination (with nevirapine/lamivudine) paediatric mini-pills. However, reassuring data are emerging about short-term stavudine use in LMICs, as this remains an important first-line regimen for young children, as well as an alternative to zidovudine for anaemic children. Zidovudine appears to be well tolerated in young children living in nonmalarious areas, and, among African children, concerns about abacavir hypersensitivity have not been substantiated.
Optimization of first-line ART regimens needs to take account of the toxicities in HIV-infected children, in particular as they will take ART much longer than adults and during the period of growth and development. The benefits of ART in pregnancy are clear, but long-term follow-up of ART-exposed infants in LMICs through integrated surveillance systems would be invaluable.
[Show abstract][Hide abstract] ABSTRACT: Pharmacokinetics, safety and antiviral activity of twice-daily fosamprenavir with or without ritonavir were evaluated in 2-18 year-old protease inhibitor (PI)-naïve and -experienced, HIV-1-infected children.Methods: Serial pharmacokinetic samples were collected at Week 2 and pre-dose samples every 4-12 weeks. Safety and plasma HIV-1 RNA were monitored every 4-12 weeks.
Twenty PI-naïve 2-<6 year-old subjects received antiretroviral treatment including unboosted fosamprenavir twice-daily, while 89 PI-naïve and -experienced 2-18 year-old subjects received fosamprenavir/ritonavir-containing therapy twice-daily. Median fosamprenavir exposure was 891 days (range 15-1805 days), with 88% exposed >48 weeks. Twice-daily doses of fosamprenavir/ritonavir 23/3 mg/kg in 2-<6 year olds, 18/3 mg/kg in ≥6 year olds and 700/100 mg in adolescents achieved plasma amprenavir exposures comparable to or higher than 700/100 mg twice daily in adults while fosamprenavir 30 mg/kg twice-daily in 2-<6 year olds led to exposures higher than 1400 mg BID in adults. The proportion of subjects with HIV-1 RNA <400 copies/mL at Week 48 was 60% for fosamprenavir and 53-74% for fosamprenavir/ritonavir [Intent-to-Treat (Exposed), Snapshot analysis]. Median increases in absolute and relative (percentage) CD4 counts from Baseline to Week 48 occurred in both the fosamprenavir (340 cells/mm; 8%) and fosamprenavir/ritonavir group (190 cells/mm; 8%). The most common adverse events were vomiting, cough, and diarrhea; 18 subjects experienced serious adverse events, including nine with suspected abacavir hypersensitivity.
Fosamprenavir regimens administered to HIV-1 infected children aged 2-18 years were generally well-tolerated and provided sustained antiviral activity over 48 weeks, with plasma amprenavir exposures comparable to or higher than adults.
[Show abstract][Hide abstract] ABSTRACT: Introduction
Guidelines in resource-poor settings have progressively included interventions to reduce postnatal HIV transmission through breast milk. In addition to HIV-free survival, infant growth and non-HIV infections should be considered. Determining the effect of these interventions on infant growth and non-HIV infections will inform healthcare decisions about feeding HIV-exposed infants. We synthesize findings from studies comparing breast to formula feeding, early weaning to standard-duration breastfeeding, breastfeeding with extended antiretroviral (ARV) to short-course ARV prophylaxis, and alternative preparations of infant formula to standard formula in HIV-exposed infants, focusing on infant growth and non-HIV infectious morbidity outcomes. The review objectives were to collate and appraise evidence of interventions to reduce postnatal vertical HIV transmission, and to estimate their effect on growth and non-HIV infections from birth to two years of age among HIV-exposed infants.
We searched PubMed, SCOPUS, and Cochrane CENTRAL Controlled Trials Register. We included randomized trials and prospective cohort studies. Two authors independently extracted data and evaluated risk of bias. Rate ratios and mean differences were used as effect measures for dichotomous and continuous outcomes, respectively. Where pooling was possible, we used fixed-effects meta-analysis to pool results across studies. Quality of evidence was assessed using the GRADE approach.
Results and discussion
Prospective cohort studies comparing breast- versus formula-fed HIV-exposed infants found breastfeeding to be protective against diarrhoea in early life [risk ratio (RR)=0.31; 95% confidence interval (CI)=0.13 to 0.74]. The effect of breastfeeding against diarrhoea [hazard ratio (HR)=0.74; 95% CI=0.57 to 0.97] and respiratory infections (HR=0.65; 95% CI=0.41 to 1.00) was significant through two years of age. The only randomized controlled trial (RCT) available showed that breastfeeding tended to be protective against malnutrition (RR=0.63; 95% CI=0.36 to 1.12). We found no statistically significant differences in the rates of non-HIV infections or malnutrition between breast-fed infants in the extended and short-course ARV prophylaxis groups.
Low to moderate quality evidence suggests breastfeeding may improve growth and non-HIV infection outcomes of HIV-exposed infants. Extended ARV prophylaxis does not appear to increase the risk for HIV-exposed infants for adverse growth or non-HIV infections compared to short-course ARV prophylaxis.
Journal of the International AIDS Society 12/2013; 16(1):18865. DOI:10.7448/IAS.16.1.18865 · 5.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective
To investigate the clinical, laboratory, epidemiological profiles and outcome in human immunodeficiency virus infected Nepalese children.
This was a hospital based prospective study. Human immunodeficiency virus-infected children presenting to pediatric immunology clinic at BP Koirala Institute of Health Sciences were enrolled and followed up.
Median age at diagnosis among 39 enrolled children was 58 months. All children acquired infection vertically. Unsafe sex (74.4%) and intravenous drug use (25.6%) were the major risk behaviors in fathers. At presentation, 20.8% children were asymptomatic, 54.0% were malnourished, 41.0% were in WHO clinical stage 1, 17.9% were in stage 4, 74.4% were anemic, 17.9% had thrombocytopenia and median CD4 count was 543. Fever, lymphadenopathy, hepatosplenomegaly, skin eruptions and oral lesions were common presenting features (16.2%, 16.2%, 13.5%, 10.8%, and 8.1% respectively out of 74 features). Tuberculosis (16.0%), chronic otitis media (12.0%), scabies (10.7%), bacterial pneumonia (9.3%) and oropharyngeal candidiasis (6.7%) were common opportunistic infections. Antiretroviral treatment was started in 18 (46.2%) cases at median age of 67 months. Median change in CD4 count at follow up was significantly different between the groups receiving and not receiving antiretroviral treatment (+192 vs. −72; P=0.045).
Infection in children is vertical. Undernutrition, anemia, fever, lymphadenopathy, hepatosplenomegaly, skin eruptions, and ear discharge are common presenting features. Opportunistic infections are common and tuberculosis is the most common opportunistic infection followed by chronic ear infection, scabies, candidiasis and bacterial pneumonia. Timely antiretroviral treatment improves immune response.
Asian Pacific Journal of Tropical Disease 06/2014; 4(3):169–175. DOI:10.1016/S2222-1808(14)60499-0
Note: This list is based on the publications in our database and might not be exhaustive.
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