Association of pol Diversity with Antiretroviral Treatment Outcomes among HIV-Infected African Children

Year: 2013

Type: article

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.

Source: PLoS ONE

DOI: 10.1371/journal.pone.0081213

Authors: Iris Chen, Leila Khaki, Jane C. Lindsey, Carrie Fry, Matthew M. Cousins, Robert F. Siliciano, Avy Violari, Paul Palumbo, Susan H. Eshleman

Institutions: Johns Hopkins University, Harvard University, Frontier Science & Technology Research Foundation, Inc., Johns Hopkins Medicine, Perinatal HIV Research Unit, Dartmouth College

Language: English

Topic: HIV/AIDS drug development and treatment

Subfield: Infectious Diseases

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,382

Funders: International Maternal Pediatric Adolescent AIDS Clinical Trials Network, National Institutes of Health, National Institute of Mental Health, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Child Health and Human Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development

OpenAlex ID: W2109549126