Title

Genome-Wide Analyses Reveal Gene Influence on HIV Disease Progression and HIV-1C Acquisition in Southern Africa

Authors

Wen Xie, Harvard T.H. Chan School of Public Health AIDS Initiative
Denis Agniel, Harvard Medical School
Andrey Shevchenko, Saint Petersburg State University
Sergey V. Malov, Saint Petersburg State University
Anton Svitin, Saint Petersburg State University
Nikolay Cherkasov, Saint Petersburg State University
Marianna K. Baum, Florida International University
Adriana Campa, Florida International University
Simani Gaseitsiwe, Harvard T.H. Chan School of Public Health AIDS Initiative
Hermann Bussmann, Harvard T.H. Chan School of Public Health AIDS Initiative
Joseph Makhema, Harvard T.H. Chan School of Public Health AIDS Initiative
Richard Marlink, Harvard T.H. Chan School of Public Health AIDS Initiative
Vladimir Novitsky, Harvard T.H. Chan School of Public Health AIDS Initiative
Tun Hou Lee, Harvard T.H. Chan School of Public Health AIDS Initiative
Tianxi Cai, Harvard T.H. Chan School of Public Health
Stephen J. O'Brien, Saint Petersburg State UniversityFollow
M. Essex, Harvard T.H. Chan School of Public Health AIDS Initiative

Document Type

Article

Publication Date

6-1-2017

Publication Title

AIDS Research and Human Retroviruses

Keywords

HIV clinical outcomes research, HIV transmission, HIV/AIDS pathogenesis, natural hosts, Restriction factors

ISSN

19318405

Volume

33

Issue/No.

6

First Page

596

Last Page

609

Abstract

Sub-Saharan Africans infected with HIV-1C make up the largest AIDS patient population in the world and exhibit large heterogeneity in disease progression before initiating antiretroviral therapy. To identify host variants associated with HIV disease progression, we performed genome-wide association studies on a total of 556 treatment-naive HIV-infected individuals in Botswana. We characterized the pattern of HIV disease progression using a novel functional principal component analysis, which can better capture longitudinal CD4 and viral load (VL) trajectories. Two single-nucleotide polymorphisms (SNPs) near HCG22 (chr6, peak variant rs2535307, combined p = 3.72 × 10-7, minor allele as risky allele) and CCNG1 (chr5, peak variant kgp22385164, combined p = 1.88 × 10-6, minor allele as risky allele) were significantly associated with CD4 and VL dynamics. Inspection of SNPs in these gene regions in a third Botswana cohort (using GWATCH) also revealed a strong association of HCG22 with HIV-1C acquisition, suggesting that this region is associated with infection as well as disease progression. Our study uncovered two genetic regions that are significant and have specific effects on HIV-1C acquisition or progression in sub-Saharan Africans, and the result suggested new potential targets for AIDS prevention and treatment. In addition, our results also indicate the possibility of using genetic markers as HIV disease progression indicators in sub-Saharan Africans to prioritize fast progressors for antiretroviral treatment.

NSUWorks Citation

Xie, Wen; Denis Agniel; Andrey Shevchenko; Sergey V. Malov; Anton Svitin; Nikolay Cherkasov; Marianna K. Baum; Adriana Campa; Simani Gaseitsiwe; Hermann Bussmann; Joseph Makhema; Richard Marlink; Vladimir Novitsky; Tun Hou Lee; Tianxi Cai; Stephen J. O'Brien; and M. Essex. 2017. "Genome-Wide Analyses Reveal Gene Influence on HIV Disease Progression and HIV-1C Acquisition in Southern Africa." AIDS Research and Human Retroviruses 33, (6): 596-609. doi:10.1089/aid.2016.0017.

DOI

10.1089/aid.2016.0017