ArticleAIDS (London, England)2017
Determinants of virological outcome and adverse events in African children treated with paediatric nevirapine fixed-dose-combination tablets.
Article in AIDS (London, England), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.
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Who cites it
6 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.
- Mortality and its predictors among human immunodeficiency virus-infected children younger than 15 years receiving antiretroviral therapy in Ethiopia: a systematic review and meta-analysis.BMC infectious diseases · 2024Pooled it
- Pharmacogenetic predictors of nevirapine pharmacokinetics in Ghanaian children living with HIV with or without TB coinfection.Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases · 2021Trial
- Causal Inference for Continuous Multiple Time Point Interventions.Statistics in medicine · 2024Article
- Determining Targets for Antiretroviral Drug Concentrations: A Causal Framework Illustrated With Pediatric Efavirenz Data From the CHAPAS-3 Trial.Pharmacoepidemiology and drug safety · 2024Article
- Determinants of nonsuppression of HIV viral load among children receiving antiretroviral therapy in the Simiyu region: a cross-sectional study.AIDS research and therapy · 2023Article
- Non-nucleoside reverse transcriptase inhibitor levels among HIV-exposed uninfected infants at the time of HIV PCR testing - findings from a tertiary healthcare facility in Pretoria, South Africa.Journal of the International AIDS Society · 2019Observational
Corrections and comments
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Authors and funding
11 authors at 1 institution in 2 countries.
Funding
Abstract
backgroundNevirapine is the only nonnucleoside reverse transcriptase inhibitor currently available as a paediatric fixed-dose-combination tablet and is widely used in African children. Nonetheless, the number of investigations into pharmacokinetic determinants of virological suppression in African children is limited, and the predictive power of the current therapeutic range was never evaluated in this population, thereby limiting treatment optimization.
methodsWe analysed data from 322 African children (aged 0.3-13 years) treated with nevirapine, lamivudine, and either abacavir, stavudine, or zidovudine, and followed up to 144 weeks. Nevirapine trough concentration (Cmin) and other factors were tested for associations with viral load more than 100 copies/ml and transaminase increases more than grade 1 using proportional hazard and logistic models in 219 initially antiretroviral treatment (ART)-naive children.
resultsPre-ART viral load, adherence, and nevirapine Cmin were associated with viral load nonsuppression [hazard ratio = 2.08 (95% confidence interval (CI): 1.50-2.90, P < 0.001) for 10-fold higher pre-ART viral load, hazard ratio = 0.78 (95% CI: 0.68-0.90, P < 0.001) for 10% improvement in adherence, and hazard ratio = 0.94 (95% CI: 0.90-0.99, P = 0.014) for a 1 mg/l increase in nevirapine Cmin]. There were additional effects of pre-ART CD4 cell percentage and clinical site. The risk of virological nonsuppression decreased with increasing nevirapine Cmin, and there was no clear Cmin threshold predictive of virological nonsuppression. Transient transaminase elevations more than grade 1 were associated with high Cmin (>12.4 mg/l), hazard ratio = 5.18 (95% CI 1.95-13.80, P < 0.001).
conclusionTreatment initiation at lower pre-ART viral load and higher pre-ART CD4 cell percentage, increased adherence, and maintaining average Cmin higher than current target could improve virological suppression of African children treated with nevirapine without increasing toxicity.
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