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

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.

SUBMITTER: Xie W

PROVIDER: S-EPMC5467143 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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

Xie Wen W Agniel Denis D Shevchenko Andrey A Malov Sergey V SV Svitin Anton A Cherkasov Nikolay N Baum Marianna K MK Campa Adriana A Gaseitsiwe Simani S Bussmann Hermann H Makhema Joseph J Marlink Richard R Novitsky Vladimir V Lee Tun-Hou TH Cai Tianxi T O'Brien Stephen J SJ Essex M M

AIDS research and human retroviruses 20170406 6

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 ...[more]

PMID: 28132517

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Project description:INTRODUCTION:Sexual behaviour change contributed to reductions in HIV incidence in eastern and southern Africa between 1990 and 2010. More recently, there are indications that non-regular partnerships have increased. However, the effect of these increases on population-level risks for HIV and other sexually transmitted infections could have been reduced by simultaneous increases in condom use. We describe recent trends in sexual behaviour and condom use within the region and assess their combined effects on population levels of sexual risk. METHODS:Nationally representative Demographic and Health Survey data on sexually active males and females (15 to 49 years) were used for 11 eastern and southern African countries (≥3 surveys for each country; 1999 to 2016) to describe trends in sexual behaviour (multiple, non-regular, and casual sexual partnerships; condom use; age at first sex). Logistic regressions tested for statistical significance of changes. Analyses were stratified by sex. RESULTS:Recent increases in multiple, non-regular, and/or casual partnerships can be found for males in 10 countries and, for females, in nine countries; five countries exhibited recent decreases in age of sexual debut. Reduction in sex without condoms with non-regular partners was observed in six countries for males and eight for females. Changes in the proportion of the overall population reporting condomless sex with non-regular partners varied between countries, with declines in six countries and increases in three. CONCLUSIONS:Extensive change in sexual behaviour occurred across eastern and southern Africa during the period of scale-up of antiretroviral therapy programmes. This includes increasing multiple and non-regular partnerships, but their potential effects on population-level sexual risks were often offset by parallel increases in condom use. Strengthening condom programmes and reintegrating communication about behavioural dimensions into combination prevention programmes could help countries to meet international targets for reductions in HIV incidence.

Dataset Information

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

Publications

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

Similar Datasets

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