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Associations of Host Genetic Variants on CD4+ Lymphocyte Count and Plasma HIV-1 RNA in Antiretroviral Naïve Children

Qin, Min PhD*; Brummel, Sean PhD*; Singh, Kumud K. PhD; Fenton, Terence EdD*; Spector, Stephen A. MD

Pediatric Infectious Disease Journal:
doi: 10.1097/INF.0000000000000330
HIV Reports
Abstract

Background: CD4+ T-lymphocyte (CD4) counts and HIV plasma RNA concentration (RNA) are 2 key HIV disease markers. The complex interplay between virus and host genetics may contribute to differences in viral set point and CD4 status. Determining the effects of host genetic variation on HIV disease markers is often complicated by the use of antiretroviral therapy. In this study, the association between genetic variants and baseline HIV RNA and CD4 counts was examined in a large cohort of antiretroviral naïve children.

Methods: Specimens from 1053 HIV-infected children were screened for single nucleotide polymorphisms in 78 regions from 17 genes. Linear regression with a robust variance estimator was used to test the association between genetic markers with HIV RNA and CD4 count, controlling for age, race/ethnicity and study. False discovery rate (FDR) controlling was used to adjust for multiple testing.

Results: The study population was 60% black, 26% Hispanic and 13% white; median age 2.35 years; 55% female. Baseline median CD4 count was 780/mm3; median log10 HIV RNA was 5.17 copies/mL. For analyses of the associations of genetic makers with baseline CD4 count, 6 HLA and 4 additional markers exhibited P < 0.05, but none met the criteria for statistical significance with FDR controlled at 0.05. For baseline HIV RNA, HLA DRB1*15, DRB1*10, B-27/57, B-14, Cw-8, B-57 were statistically significant with FDR controlled at 0.05.

Conclusions: These results provide strong evidence that HLA DRB1*15, DRB1*10, B-27/57, B-14, Cw-8, B-57 are associated with HIV RNA and play a role in HIV pathogenesis in infected children.

Author Information

From the *Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, MA; and University of California, San Diego, La Jolla, CA and Rady Children’s Hospital, San Diego, CA.

Accepted for publication February 5, 2014.

This research was supported in part by the Pediatric AIDS Clinical Trial Group (U01 AI041089) and International Maternal Perinatal Adolescent AIDS Clinical Trials Network. Overall support for the International Maternal Pediatric Adolescent AIDS Clinical Trials Group was provided by the National Institute of Allergy and Infectious Diseases (U01 AI068632), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (contract number N01-DK-9-001/HHSN267200800001C), and the National Institute of Mental Health [AI068632], 1R01NS077874 (S.A.S.) and 5R01MH085608 (K.K.S.).

The authors have no other funding or conflicts of interest to disclose.

Address for correspondence: Stephen A. Spector, MD, 9500 Gilman Drive, Stein Clinical Research Building, MC 0672, La Jolla, CA 92093-0672. E-mail: saspector@ucsd.edu.

© 2014 by Lippincott Williams & Wilkins, Inc.