Drug Resistance Mutations in a Population Before Antiretroviral Therapy Initiation in Northern South Africa.
AIDS research and human retroviruses(2022)
摘要
South Africa introduced the "diagnose and treat" universal HIV treatment program in September 2016. This program enables all identified HIV-positive patients to immediately start first-line antiretroviral therapy (ART). However, the presence of drug-resistant (DR) viruses in the drug-naive population complicates the choice of ART. We used next-generation sequencing (NGS) to determine the prevalence and diversity of HIV DR mutations in patients entering HIV treatment programs in northern South Africa. RNA was isolated from plasma of drug-naive HIV-1-infected patients. Using reverse transcriptase polymerase chain reaction, the HIV-1- gene comprising the complete protease (PR) and the first 900 bp of reverse transcriptase (RT) was amplified and sequenced on an Illumina MiniSeq platform. Consensus sequences were derived at >20% threshold and at >5% threshold using Geneious PRIME software version 2020.1.2. HIV-1 surveillance drug resistance mutations (SDRM) were inferred using Calibrated Population Resistance tool in HIV Drug Resistance Database. Viral subtypes were determined using REGA and RIP genotyping tools. The HIV PR/RT region was successfully sequenced from 241 patients. From these, 23 (9.5%) had at least one SDRM detected at >20% threshold, with a prevalence of 9.5% ( = 18), 3% ( = 7), and 0.4% ( = 1) for non-nucleoside reverse transcriptase inhibitors (NNRTI), nucleoside reverse transcriptase inhibitors (NRTI), and protease inhibitors (PI), respectively. The number of patients with SDRM increased to 31 (12.9%) when minority variants were accounted for at >5% threshold. The most frequent SDRMs based on drug class were; K103N (7.9%-NNRTI), K65R (2.5%-NRTI), and D30N (0.8%-PI). Four cases of dual NRTI/NNRTI mutations were identified. All consensus sequences were subtype C, except three, which were C/A1, C/F1, and C/G recombinants. NGS analysis confirms that individuals entering HIV treatment programs in northern South Africa, habor moderate levels of SDRM, including cases of dual-class drug resistance. Further SDRM studies may be required to better understand resistance in the drug-naive population in the era of "diagnose and treat" in Limpopo Province, South Africa.
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关键词
South Africa,drug-naive population,human immunodeficiency virus,next-generation sequencing,surveillance drug resistance mutation
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