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Use of a High Resolution Melting Assay to Analyze HIV Diversity in HIV-infected Ugandan Children

James, Maria M. BA*; Wang, Lei PhD; Donnell, Deborah PhD; Cousins, Matthew M. MS*; Barlow-Mosha, Linda MD, MPH§; Fogel, Jessica M. MS*; Towler, William I. MS*; Agwu, Allison L. MD, ScM; Bagenda, Danstan PhD§║; Mubiru, Micheal BS, DMS**; Musoke, Philippa MB ChB, PhD§††; Eshleman, Susan H. MD, PhD*

The Pediatric Infectious Disease Journal: November 2012 - Volume 31 - Issue 11 - p e222–e228
doi: 10.1097/INF.0b013e3182678c3f
HIV Reports

Background: We used a novel high resolution melting (HRM) diversity assay to analyze HIV diversity in Ugandan children (age 0.6–12.4 years) who were enrolled in an observational study of antiretroviral treatment (ART). Children were maintained on ART if they were clinically and immunologically stable.

Methods: HIV diversity was measured before ART (baseline) in 76 children and after 48 or 96 weeks of ART in 14 children who were not virally suppressed. HIV diversity (expressed as HRM scores) was measured in 6 regions of the HIV genome (2 in gag, 1 in pol, 3 in env).

Results: Higher baseline HRM scores were significantly associated with older age (≥2 years, P ≤ 0.001 for all 6 regions). HRM scores from different regions were weakly correlated. Higher baseline HRM scores in 3 regions (1 in gag, 2 in env) were associated with ART failure. HIV diversity was lower in 4 regions (2 in gag, 1 in pol, 1 in env) after 48–96 weeks of nonsuppressive ART compared with baseline.

Conclusions: Higher levels of HIV diversity were observed in older children before ART, and higher levels of diversity in some regions of the HIV genome were associated with ART failure. Prolonged exposure to nonsuppressive ART was associated with a significant decrease in viral diversity in selected regions of the HIV genome.

From the *Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center and Department of Global Health, University of Washington, Seattle, WA; §Makerere University-Johns Hopkins University Research Collaboration (MU-JHU) Kampala, Uganda; Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD; Department of Epidemiology and Biostatistics, Makerere University School of Public Health, Kampala, Uganda; **Department of Research Coordination, Makerere University-Johns Hopkins University Research Collaboration (MU-JHU), Baltimore, MD; and ††Department of Paediatrics and Child Health, School of Medicine, Makerere University, Kampala, Uganda.

Accepted for publication June 30, 2012.

William I. Towler is currently at Ohio State University Medical Center, Biomedical Informatics, Columbus, OH.

Supported by (1) the National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIAID, NIH. 1R01-AI095068); (2) the HIV Prevention Trials Network (HPTN) sponsored by the NIAID, the Eunice Kennedy Shriver National Institutes of Child Health and Human Development (NICHD), National Institute on Drug Abuse, National Institute of Mental Health and Office of AIDS Research, NIH, Department of Health and Human Resources (U01-AI068613, UM1-AI068613, UM1-AI068617); (3) the International Maternal Pediatric and Adolescent AIDS Clinical Trials Group, NIAID, NICHD, NIH (U01-AI068632); and (4) the International Leadership Award, Elizabeth Glaser Pediatric AIDS Foundation. The authors have no other funding or conflicts of interest to disclose.

Address for correspondence: Susan H. Eshleman, MD, PhD, Department of Pathology, Johns Hopkins Medical Institutions, Ross Bldg. 646, 720 Rutland Ave., Baltimore, MD 21205. E-mail: seshlem@jhmi.edu.

© 2012 Lippincott Williams & Wilkins, Inc.