Antiretroviral therapy blocks natural selection on protective and disease-susceptible HLA-B alleles in HIV-1 infection

= 0.002). By contrast, in contemporary antenatal KwaZulu-Natal cohorts in the ART era (2015-2025) the impact of HLA-B on HIV-1 disease outcome and vertical transmission is dramatically reduced. Using these and reported data, we constructed a model to estimate the impact of HIV-1 on HLA-B frequencies in KwaZulu-Natal, both in the prevailing setting of ART and in a hypothetical counterfactual scenario where ART was never rolled out. Over the 45-y period 1990-2035, in the absence of ART, the proportion of the population possessing any "protective" HLA-B allele was projected to increase from 23 to 42% (allele frequencies increasing from 0.12 to 0.24), and the proportion of the population possessing any "disease-susceptible" HLA-B allele was projected to decrease from 28 to 18% (allele frequencies declining from 0.15 to 0.092). The introduction of ART radically slows HLA-B frequency change. These data therefore demonstrate the potential for natural selection from an infectious disease to alter human population genetics within decades, and for the successful roll-out of therapy to halt this process.

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Publication Details

Journal
Proceedings of the National Academy of Sciences
Published
2026-04-27
DOI
https://doi.org/10.1073/pnas.2502683123
Primary Topic
HIV Research and Treatment
Type
article
Field-Weighted Citation Impact
0.00

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article

Antiretroviral therapy blocks natural selection on protective and disease-susceptible HLA-B alleles in HIV-1 infection

Mary Carrington, Nicholas Herbert, Gabriela Cromhout, Philip Goulder et al.
Proceedings of the National Academy of Sciences
HIV Research and Treatment
article

Antiretroviral therapy blocks natural selection on protective and disease-susceptible HLA-B alleles in HIV-1 infection

Mary Carrington, Nicholas Herbert, Gabriela Cromhout, Philip Goulder, Bridget S. Penman, Kogielambal Chinniah, Jeroen van Lobenstein, Veron Ramsuran, Noxolo Mchunu, Roopesh Bhoola, Nomonde Bengu, Sunetra Gupta, Rowena Fillis, Krista L. Dong, Christian Brander, Thilona Arumugam, Samantha Kannie, Malini Krishna, Thumbi Ndung’u, Constant Kapongo
article en

Abstract

= 0.002). By contrast, in contemporary antenatal KwaZulu-Natal cohorts in the ART era (2015-2025) the impact of HLA-B on HIV-1 disease outcome and vertical transmission is dramatically reduced. Using these and reported data, we constructed a model to estimate the impact of HIV-1 on HLA-B frequencies in KwaZulu-Natal, both in the prevailing setting of ART and in a hypothetical counterfactual scenario where ART was never rolled out. Over the 45-y period 1990-2035, in the absence of ART, the proportion of the population possessing any "protective" HLA-B allele was projected to increase from 23 to 42% (allele frequencies increasing from 0.12 to 0.24), and the proportion of the population possessing any "disease-susceptible" HLA-B allele was projected to decrease from 28 to 18% (allele frequencies declining from 0.15 to 0.092). The introduction of ART radically slows HLA-B frequency change. These data therefore demonstrate the potential for natural selection from an infectious disease to alter human population genetics within decades, and for the successful roll-out of therapy to halt this process.

Proceedings of the National Academy of SciencesVol. 123(19)
Universitat de Vic - Universitat Central de Catalunya (ES), Institució Catalana de Recerca i Estudis Avançats (ES), Harvard University (US), Centre for the AIDS Programme of Research in South Africa (ZA), Cancer Institute (WIA) (IN), Ragon Institute of MGH, MIT and Harvard (US), University of Oxford (GB), Massachusetts General Hospital (US), Stanger Hospital (ZA), Queen Nandi Regional Hospital (ZA), Medawar Building for Pathogen Research (GB), Western Regional Hospital (NP), Africa Health Research Institute (ZA), Frederick National Laboratory for Cancer Research (US), Laboratoire d’immunologie intégrative du cancer (FR), Mahatma Gandhi Memorial Hospital (ZA), Center for Cancer Research (US), Immunomedics (Germany) (DE), Institute of Infection and Immunity (CA), University College London (GB), University of KwaZulu-Natal (ZA)
Wellcome Trust, National Institutes of Health
Good health and well-being
Openalex Percentile: Top 10%
HIV Research and Treatment
DOIOpen Access PDFOpenAlex
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