title: Association of pol diversity with antiretroviral treatment outcomes among HIV-infected African children.
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-naïve African children, higher levels of HIV diversity in the HIV pol region prior to ART initiation were associated with better treatment outcomes.
authors: Dept. of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors: Iris
authors: I
authors: Chen
authors: Leila
authors: L
authors: Khaki
authors: Jane C
authors: JC
authors: Lindsey
authors: Carrie
authors: C
authors: Fry
authors: Matthew M
authors: MM
authors: Cousins
authors: Robert F
authors: RF
authors: Siliciano
authors: Avy
authors: A
authors: Violari
authors: Paul
authors: P
authors: Palumbo
authors: Susan H
authors: SH
authors: Eshleman
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D044822:Biodiversity; D002675:Child, Preschool; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007223:Infant; D008297:Male; D016896:Treatment Outcome; D054302:pol Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*
chemical_list: D019380:Anti-HIV Agents; D054302:pol Gene Products, Human Immunodeficiency Virus