African Ancestry Influences CCR5 2459G>A Genotype-Associated Virologic Success of Highly Active Antiretroviral Therapy

Cheruvu, Vinay K. PhD*; Igo, Robert P. Jr PhD; Jurevic, Richard J. DDS, PhD; Serre, David PhD§; Zimmerman, Peter A. PhD; Rodriguez, Benigno MD; Mehlotra, Rajeev K. PhD

JAIDS Journal of Acquired Immune Deficiency Syndromes: 1 May 2014 - Volume 66 - Issue 1 - p 102–107
doi: 10.1097/QAI.0000000000000129
Epidemiology and Prevention

Introduction: In a North American, HIV-positive, highly active antiretroviral therapy (HAART)-treated, adherent cohort of self-identified white and black patients, we previously observed that chemokine (C-C motif) receptor 5 (CCR5) −2459G>A genotype had a strong association with time to achieve virologic success (TVLS) in black but not in white patients.

Methods: Using 128 genome-wide ancestry informative markers, we performed a quantitative assessment of ancestry in these patients (n = 310) to determine (1) whether CCR5 −2459G>A genotype is still associated with TVLS of HAART when ancestry, not self-identified race, is considered and (2) whether this association is influenced by varying African ancestry.

Results: We found that the interaction between CCR5 −2459G>A genotype and African ancestry (≤0.125 vs. ≥0.425 and <0.71 vs. ≥0.71) was significantly associated with TVLS (GG compared with AA, P = 0.044 and 0.018, respectively). Furthermore, the association between CCR5 −2459G>A genotype and TVLS was stronger in patients with African ancestry ≥0.71 than in patients with African ancestry ≥0.452, in both Kaplan–Meier (log-rank P = 0.039 and 0.057, respectively, for AA, GA, and GG) and Cox proportional hazards regression (relative hazard for GG compared with AA 2.59 [95% confidence interval: 1.27 to 5.22; P = 0.01] and 2.26 [95% confidence interval: 1.18 to 4.32; P = 0.01], respectively) analyses.

Conclusions: We observed that the association between CCR5 −2459G>A genotype and TVLS of HAART increased with stronger African ancestry. Understanding the genomic mechanisms by which African ancestry influences this association is critical and requires further studies.

*Department of Biostatistics, Environmental Health Sciences, and Epidemiology, College of Public Health, Kent State University, Kent, OH;

Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH;

Department of Biological Sciences, Case Western Reserve University School of Dental Medicine, Cleveland, OH;

§Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH;

Center for Global Health and Diseases, Case Western Reserve University School of Medicine, Cleveland, OH; and

Department of Medicine, Division of Infectious Diseases and HIV Medicine, Case Western Reserve University School of Medicine, Cleveland, OH (Dr Richard J. Jurevic, DDS, PhD, is now with the Department of Oral Diagnostics, School of Dentistry, West Virginia University, Morgantown, WV).

Correspondence to: Rajeev K. Mehlotra, PhD, Center for Global Health and Diseases, Biomedical Research Building, 409A, 2109 Adelbert Road, Cleveland, OH 44106-2624 (e-mail: rkm@case.edu).

Supported by a development award from the Center for AIDS Research University Hospitals Case Medical Center (NIH grant AI36219) (R.K.M.); an Infectious Diseases research support from STERIS Corporation (R.K.M. and B.R.); a large pilot grant from Case Western Reserve University/Cleveland Clinic CTSA grant number UL1RR024989 (National Center for Research Resources) (R.K.M.); and the National Institute of Dental and Craniofacial Research (NIH grant 1P01DE019759, Project 4 to R.J.J.).

Presented in part at the XIX International AIDS Conference, July 2012; Washington DC. (Abstract no. TUPE009).

The authors have no conflicts of interest to disclose.

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Received February 07, 2014

Accepted February 07, 2014

© 2014 by Lippincott Williams & Wilkins