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

Jane C. Lindsey, Michael D. Hughes, Avy Violari, Susan H. Eshleman, Elaine J. Abrams, Mutsa Bwakura-Dangarembizi, Linda Barlow-Mosha, Portia Kamthunzi, Pauline M. Sambo, Mark F. Cotton, Harry Moultrie, Sandhya Khadse, Werner Schimana, Raziya Bobat, Bonnie Zimmer, Elizabeth Petzold, Lynne M. Mofenson, Patrick Jean-Philippe, Paul Palumbo

Research output: Contribution to journalArticle

Abstract

Background: In a randomized trial comparing nevirapine (NVP)-based 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 by week 24] aged 2 months to 3 years, we assessed whether clinical, virologic, immunologic and safety outcomes varied by prior single-dose NVP exposure (PrNVP) for prevention of motherto- child HIV transmission and other covariates. Methods: Efficacy was assessed by time to ART discontinuation or virologic failure, virologic failure/death and death; safety by time to ART discontinuation because of a protocol-defined toxicity and first ≥ grade 3 adverse event; immunology and growth by changes in CD4%, weight/height World Health Organization 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 NVPbased ART for efficacy and safety outcomes; however, those on NVP had larger improvements in CD4%, weight and height z-scores. Lower pretreatment CD4% and higher HIV-1 RNA levels were associated with reduced efficacy, lower pretreatment CD4% with shorter time to ART discontinuation because of 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 breast-feeding, sex, HIV-1 subtype, age, pretreatment CD4%, HIV-1 RNA or World Health Organization disease stage. This finding should be considered when selecting an ART regimen for young children.

Original languageEnglish (US)
Pages (from-to)846-854
Number of pages9
JournalPediatric Infectious Disease Journal
Volume33
Issue number8
DOIs
StatePublished - Aug 2014

Keywords

  • Africa
  • Antiretroviral therapy
  • Clinical trials
  • Pediatrics
  • Prevention of mother-to-child transmission

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Microbiology (medical)
  • Infectious Diseases

Fingerprint Dive into the research topics of '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'. Together they form a unique fingerprint.

  • Cite this

    Lindsey, J. C., Hughes, M. D., Violari, A., Eshleman, S. H., Abrams, E. J., Bwakura-Dangarembizi, M., Barlow-Mosha, L., Kamthunzi, P., Sambo, P. M., Cotton, M. F., Moultrie, H., Khadse, S., Schimana, W., Bobat, R., Zimmer, B., Petzold, E., Mofenson, L. M., Jean-Philippe, P., & Palumbo, P. (2014). 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. Pediatric Infectious Disease Journal, 33(8), 846-854. https://doi.org/10.1097/INF.0000000000000337