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Trends in pretreatment HIV-1 drug resistance in antiretroviral therapy-naive adults in South Africa, 2000-2016: A pooled sequence analysis
Chimukangara, B Lessells, R.J Rhee, S-Y Giandhari, J Kharsany, A.B.M Naidoo, K Lewis, L Cawood, C Khanyile, D Ayalew, K.A
Chimukangara, B
Lessells, R.J
Rhee, S-Y
Giandhari, J
Kharsany, A.B.M
Naidoo, K
Lewis, L
Cawood, C
Khanyile, D
Ayalew, K.A
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Abstract
Background: South Africa has the largest public antiretroviral therapy (ART) programme in the world. We assessed temporal trends in pretreatment HIV-1 drug resistance (PDR) in ART-naïve adults from South Africa.
Methods: We included datasets from studies conducted between 2000 and 2016, with HIV-1 pol sequences from more than ten ART-naïve adults. We analysed sequences for the presence of 101 drug resistance mutations. We pooled sequences by sampling year and performed a sequence-level analysis using a generalized linear mixed model, including the dataset as a random effect.
Findings: We identified 38 datasets, and retrieved 6880 HIV-1 pol sequences for analysis. The pooled annual prevalence of PDR remained below 5% until 2009, then increased to a peak of 11·9% (95% confidence interval (CI) 9·2-15·0) in 2015. The pooled annual prevalence of non-nucleoside reverse-transcriptase inhibitor (NNRTI) PDR remained below 5% until 2011, then increased to 10.0% (95% CI 8.4-11.8) by 2014. Between 2000 and 2016, there was a 1.18-fold (95% CI 1.13-1.23) annual increase in NNRTI PDR (p < 0.001), and a 1.10-fold (95% CI 1.05-1.16) annual increase in nucleoside reverse-transcriptase inhibitor PDR (p = 0.001).
Interpretation: Increasing PDR in South Africa presents a threat to the efforts to end the HIV/AIDS epidemic. These findings support the recent decision to modify the standard first-line ART regimen, but also highlights the need for broader public health action to prevent the further emergence and transmission of drug-resistant HIV.
Source of funding: This research project was funded by the South African Medical Research Council (MRC) with funds from National Treasury under its Economic Competitiveness and Support Package.
Disclaimer: The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of CDC.
Description
Date
2019-03
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Elsevier
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Keywords
Antiretroviral therapy,HIV,Molecular epidemiology,Pooled sequence analysis,Pre-treatment drug resistance,South Africa,Surveillance
Citation
Chimukangara B, Lessells RJ, Rhee SY, Giandhari J, Kharsany ABM, Naidoo K, Lewis L, Cawood C, Khanyile D, Ayalew KA, Diallo K, Samuel R, Hunt G, Vandormael A, Stray-Pedersen B, Gordon M, Makadzange T, Kiepiela P, Ramjee G, Ledwaba J, Kalimashe M, Morris L, Parikh UM, Mellors JW, Shafer RW, Katzenstein D, Moodley P, Gupta RK, Pillay D, Abdool Karim SS, de Oliveira T. Trends in Pretreatment HIV-1 Drug Resistance in Antiretroviral Therapy-naive Adults in South Africa, 2000-2016: A Pooled Sequence Analysis. EClinicalMedicine. 2019 Mar 18;9:26-34. doi: 10.1016/j.eclinm.2019.03.006.