Document Type

Article

Publication Date

11-27-2013

Publication Title

PloS One

Department

Geisel School of Medicine

Abstract

Background: In HIV-infected children, viral diversity tends to increase with age in the absence of antiretroviral treatment (ART). We measured HIV diversity in African children (ages 6–36 months) enrolled in a randomized clinical trial comparing two ART regimens (Cohort I of the P1060 trial). Children in this cohort were exposed to single dose nevirapine (sdNVP) at birth. Methods: HIV diversity was measured retrospectively using a high resolution melting (HRM) diversity assay. Samples were obtained from 139 children at the enrollment visit prior to ART initiation. Six regions of the HIV genome were analyzed: two in gag , one in pol , and three in env . A single numeric HRM score that reflects HIV diversity was generated for each region; composite HRM scores were also calculated (mean and median for all six regions). Results: In multivariable median regression models using backwards selection that started with demographic and clinical variables, older age was associated with higher HRM scores (higher HIV diversity) in pol (P = 0.005) and with higher mean (P = 0.014) and median (P , 0.001) HRM scores. In multivariable models adjusted for age, pre-treatment HIV viral load, pre- treatment CD4%, and randomized treatment regimen, higher HRM scores in pol were associated with shorter time to virologic suppression (P = 0.016) and longer time to study endpoints (virologic failure [VF], VF/death, and VF/off study treatment; P , 0.001 for all measures). Conclusions:In this cohort of sdNVP-exposed, ART-naı ̈ ve African children, higher levels of HIV diversity in the HIV pol region prior to ART initiation were associated with better treatment outcomes

DOI

10.1371/journal.pone.0081213

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