Predicted dolutegravir resistance in people living with HIV in South Africa during 2020–35: a modelling study

作者：Tom Loosli, Nuri Han, Anthony Hauser, Johannes Josi, Suzanne M Ingle, Ard van Sighem, Linda Wittkop, Jörg Janne Vehreschild, Francesca Ceccherini‐Silberstein, Gary Maartens, M. John Gill, Caroline Sabin, Leigh F. Johnson, Richard Lessells, Huldrych F. Günthard, Matthias Egger, Roger D. Kouyos · 发表于：The Lancet Global Health · 年份：2025 · DOI：10.1016/s2214-109x(24)00553-9 · 被引用次数：27 · 研究领域：HIV/AIDS drug development and treatment、HIV Research and Treatment、HIV-related health complications and treatments

BACKGROUND: In response to increasing resistance to non-nucleoside reverse transcriptase inhibitors, millions of people living with HIV have switched to dolutegravir-based antiretroviral therapy, so understanding the possible emergence of dolutegravir resistance is essential. We aimed to predict how dolutegravir resistance in South Africa will change over time. METHODS: For this modelling study, we used the Modelling Antiretroviral Drug Resistance in South Africa (MARISA) model, a deterministic compartmental model calibrated to reproduce the HIV-1 epidemic in South Africa from 2005 to 2035 using data from the International Epidemiology Databases to Evaluate AIDS collaboration and the literature. Key parameters for modelling dolutegravir-resistance evolution were acquisition rates of dolutegravir-resistance mutations, reversion rates of dolutegravir-resistance mutations, the effect of resistance to nucleoside reverse transcriptase inhibitors on dolutegravir-resistance acquisition, the effect of dolutegravir resistance on dolutegravir-treatment efficacy, the probability of transmitting dolutegravir drug-resistance mutations compared with the probability of transmitting wild-type HIV, and the proportion of people with virologic failure on dolutegravir-based antiretroviral therapy with detectable drug levels. Model outcomes were estimated transmitted dolutegravir resistance and estimated acquired dolutegravir resistance. FINDINGS: We estimated a substantial increase in the number...