Predictors of Virologic and Clinical Response to Nevirapine versus Lopinavir/Ritonavir-based Antiretroviral Therapy in Young Children With and Without Prior Nevirapine Exposure for the Prevention of Mother-to-child HIV Transmission

Abstract

Background In a randomized trial comparing nevirapine (NVP)- versus lopinavir/ritonavir (LPV/r)– based antiretroviral therapy (ART) in HIV-infected children (primary endpoint discontinuation of study treatment for any reason or virologic failure (VF) by week 24) aged two months to three years, we assessed whether clinical, virologic, immunologic and safety outcomes varied by prior single-dose NVP exposure (PrNVP) for prevention of mother-to-child HIV transmission and other covariates. Methods Efficacy was assessed by time to ART discontinuation or VF, VF/death, and death; safety by time to ART discontinuation due to a protocol-defined toxicity and first ≥ grade 3 adverse event; immunology and growth by changes in CD4%, weight/height WHO z-scores from entry to week 48. Cox proportional hazards and linear regression models were used to test whether treatment differences depended on PrNVP exposure and other covariates. Results Over a median follow-up of 48 (PrNVP) and 72 (No PrNVP) weeks, there was no evidence of differential treatment effects by PrNVP exposure or any other covariates. LPV/r – based ART was superior to NVP-based ART for efficacy and safety outcomes but those on NVP had larger improvements in CD4%, weight and height z-scores. Lower pre-treatment CD4% and higher HIV-1 RNA levels were associated with reduced efficacy, lower pre-treatment CD4% with shorter time to ART discontinuation due to a protocol-defined toxicity, and no PrNVP with shorter time to first grade ≥3 adverse event. Conclusions Differences between LPV/r and NVP ART in efficacy, safety, immunologic and growth outcomes did not depend on PrNVP exposure, prior breastfeeding, sex, HIV-1 subtype, age, pre-treatment CD4%, HIV-1 RNA or WHO disease stage. This finding should be considered when selecting an ART regimen for young children.

Nevirapine- Versus Lopinavir/Ritonavir-Based Antiretroviral Therapy in HIV-Infected Infants and Young Children: Long-term Follow-up of the IMPAACT P1060 Randomized Trial

“…Details of methods for the weighted models are given in the Supplementary Appendix. We pooled data from both cohorts, following analyses demonstrating that previous NVP exposure was not associated with differential treatment outcomes between the 2 randomization arms [16].…”

HIV/AIDS Treatment Failure and its Determinant Factors among First Line HAART Patients at Felege-Hiwot Referral Hospital, Bahir Dar, Northwest Ethiopia

“…Inappropriate prescribing, treatment interruptions due to suboptimal patient adherence, poor patient retention on ART, or late initiation or when stock-outs occur. These factors have been shown to be associated with the development of HIV treatment failure [6,8,20].…”

“…Monitoring of ART program factors known to be associated with the emergence of treatment failure for the purpose of improving programmatic functioning, may minimize the emergence of preventable HIVDR, especially at ART sites where viral load is not routinely available [6,8,18,19]. Inappropriate prescribing, treatment interruptions due to suboptimal patient adherence, poor patient retention on ART, or late initiation or when stock-outs occur.…”

“…Due to HIV's error-prone replication, high mutation rate and viral recombination, development of some HIV drug resistance (HIVDR) is inevitable, even with appropriate ART prescribing and adherence [5][6][7][8]. HIVDR has significant human and financial implications: it limits treatment options.…”

Pediatric HIV: Progress on Prevention, Treatment, and Cure

“…There is increasing evidence confirming the benefit of starting LPV/r-based ART as first-line therapy in infants regardless of PMTCT history [67**,68]. Unfortunately in low resource settings programs have been slow to incorporate LPV/r into their first line regimens and nevirapine-based ART is more often prescribed for infants and young children [69].…”