title: Nevirapine Resistance in Previously Nevirapine-Unexposed HIV-1-Infected Kenyan Infants Initiating Early Antiretroviral Therapy.
abstract: Nevirapine (NVP) resistance occurs frequently in infants following NVP use in prevention of mother-to-child transmission (PMTCT) regimens. However, among previously NVP-unexposed infants treated with NVP-antiretroviral therapy (ART), the development and impact of NVP resistance have not been well characterized. In a prospective clinical trial providing early ART to HIV-infected infants <5 months of age in Kenya (OPH03 study), we followed NVP-unexposed infants who initiated NVP-ART for 12 months. Viral loads were assessed and resistance determined using a population-based genotypic resistance assay. Of 99 infants screened, 33 had no prior NVP exposure, 22 of whom were initiated on NVP-ART. Among 19 infants with follow-up, seven (37%) infants developed resistance: one at 3 months and six at 6 months after ART initiation. The cumulative probability of NVP resistance was 5.9% at 3 months and 43.5% at 6 months. Baseline HIV RNA levels (p=0.7) and other characteristics were not associated with developing resistance. Post-ART, higher virus levels at visits preceding the detection of resistance were significantly associated with increased detection of resistance (p=0.004). Virus levels after 6 and 12 months of ART were significantly higher in infants with resistance than those without (p=0.007, p=0.030, respectively). Among infants without previous NVP exposure, development of NVP resistance was frequent and was associated with virologic failure during the first year of ART. Earlier development of NVP resistance in infants than in adults initiating NVP-ART may be due to longer viremia following ART or inadequate NVP levels resulting from NVP lead-in dosing. The development of NVP resistance may, in part, explain the superiority of protease inhibitor-based ART in infants.
authors.affiliation: 1 Department of Medical Microbiology, University of Nairobi , Nairobi, Kenya .|2 Department of Global Health, University of Washington , Seattle, Washington.|3 Kenya Medical Research Institute , Nairobi, Kenya .
authors.forename: Bhavna H
authors.initials: BH
authors.lastname: Chohan
authors.affiliation: 2 Department of Global Health, University of Washington , Seattle, Washington.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Tapia
authors.affiliation: 2 Department of Global Health, University of Washington , Seattle, Washington.
authors.forename: Sarah
authors.initials: S
authors.lastname: Benki-Nugent
authors.affiliation: 4 Department of Pediatrics, University of Nairobi , Nairobi, Kenya .
authors.forename: Brian
authors.initials: B
authors.lastname: Khasimwa
authors.affiliation: 3 Kenya Medical Research Institute , Nairobi, Kenya .
authors.forename: Musa
authors.initials: M
authors.lastname: Ngayo
authors.affiliation: 4 Department of Pediatrics, University of Nairobi , Nairobi, Kenya .
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Maleche-Obimbo
authors.affiliation: 4 Department of Pediatrics, University of Nairobi , Nairobi, Kenya .
authors.forename: Dalton
authors.initials: D
authors.lastname: Wamalwa
authors.affiliation: 5 Fred Hutchinson Cancer Research Center , Seattle, Washington.
authors.forename: Julie
authors.initials: J
authors.lastname: Overbaugh
authors.affiliation: 2 Department of Global Health, University of Washington , Seattle, Washington.|6 Department of Epidemiology, University of Washington , Seattle, Washington.|7 Department of Medicine, University of Washington , Seattle, Washington.|8 Department of Pediatrics, University of Washington , Seattle, Washington.
authors.forename: Grace
authors.initials: G
authors.lastname: John-Stewart
mesh_terms: D044966:Anti-Retroviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D024882:Drug Resistance, Viral; D005260:Female; D060005:Genotyping Techniques; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D007223:Infant; D007630:Kenya; D008137:Longitudinal Studies; D008297:Male; D020125:Mutation, Missense; D019829:Nevirapine / Q000494:pharmacology* / Q000627:therapeutic use; D011446:Prospective Studies; D055502:Secondary Prevention; D013997:Time Factors; D019562:Viral Load
chemical_list: D044966:Anti-Retroviral Agents; D019829:Nevirapine
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