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Vitamin Drelated Host Genetic Variants Alter HIV Disease Progression in Children

Moodley, Amaran MD*†; Qin, Min PhD; Singh, Kumud K. PhD*†; Spector, Stephen A. MD*†

Pediatric Infectious Disease Journal: November 2013 - Volume 32 - Issue 11 - p 1230–1236
doi: 10.1097/INF.0b013e31829e4d06
HIV Reports

Background: Vitamin D deficiency is common in HIV infection and has been associated with advanced disease. This study investigated whether vitamin D–related genetic variants were associated with disease progression in HIV-infected children.

Methods: The Fok-I (C/T), Bsm-I (G/A), GC (A/C), DHCR7 (G/T) and CYP2R1 (G/A) genetic variants were detected by real-time polymerase chain reaction in HIV-infected children who participated in the Pediatric AIDS Clinical Trials Group P152 and P300 protocols, which predated the availability of effective combination antiretroviral therapy. The primary endpoints included time to progression to the first HIV-related disease endpoint (≥2 opportunistic infection, weight growth failure) or death, which constituted the progression-free survival. Analyses were performed for age >2 years and ≤2 years separately adjusting for race and treatment effect.

Results: Of the 998 children evaluated, 139 experienced HIV disease progression. For children >2 years, rapid disease progression was associated with the DHCR7 G allele compared with the T allele (G/G vs. T/T: hazard ratio [HR] = 5.0, P = 0.035; G/T vs. T/T: HR = 4.5, P = 0.042; G/G+G/T vs. T/T: HR = 4.8, P = 0.036) and the Bsm-I A allele compared with the G allele (A/G vs. G/G: HR = 2.2, P = 0.014 and A/G+A/A vs. G/G: HR = 2.0, P = 0.026). In children ≤2 years, the Bsm-I A allele increased the risk of disease progression in Hispanics (A/A vs. G/A+G/G: HR = 2.8, P = 0.03 and A/A vs. G/G: HR = 2.8, P = 0.046) and whites (A/A vs. G/G: HR = 6.6, P = 0.025 and A/A vs. G/A+G/G: HR = 3.6, P = 0.038).

Conclusions: Vitamin D–related host genetic variants that alter the availability and activity of vitamin D are associated with risk of HIV disease progression in children and may vary by age and race.

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

Accepted for publication May 1, 2013.

Presented in part at CROI 2012, 19th Conference on Retroviruses and Opportunistic Infections, Seattle, March 5–8, 2012.

This research was supported in part by National Institutes of Health grants R01 NS077874, R21AI084573, R01MH095585, the Thrasher Research Foundation and the International Maternal Perinatal Adolescent AIDS Clinical Trials (IMPAACT) Network. Overall support for the IMPAACT Group was provided by the National Institute of Allergy and Infectious Diseases (NIAID) [U01 AI068632], the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and the National Institute of Mental Health [AI068632]. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. This work was supported by the Statistical and Data Analysis Center at Harvard School of Public Health, under the National Institute of Allergy and Infectious Diseases cooperative agreement #5 U01 AI41110 with the Pediatric AIDS Clinical Trials Group and U01 AI068616 with the IMPAACT Group. Support of the sites was provided by the NIAID and the NICHD International and Domestic Pediatric and Maternal HIV Clinical Trials Network funded by NICHD (contract number N01-DK-9-001/HHSN267200800001C). 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.

© 2013 by Lippincott Williams & Wilkins, Inc.