Prevalence and diversity of HIV drug resistance mutations in patients entering treatment program in Northern South Africa
20th International Conference on AIDS and STIs in Africa (ICASA)
Kigali, Rwanda
Background: In September 2016, South Africa introduced the universal HIV treatment programme, that is, ‘diagnose and treat.’ Transmission of drug resistant viruses complicates the choice of first line treatment regimen at the population level. This study aimed to determine the prevalence and diversity of HIV drug resistance mutations in patients entering HIV treatment programmes in northern South Africa.
Methods: Proviral DNA was isolated from peripheral blood mononuclear cells of 257 of supposed drug naïve HIV-1 infected patients to entering treatment programmes in northern South Africa. A fragment of the HIV pol gene, comprising the complete protease and the first 421 amino acids of reverse transcriptase was amplified by nested PCR. Amplicons were sequenced on an Illumina MiniSeq Next Generation Sequencing (NGS) platform. Consensus sequences were derived with minority variants cut-offs of >20%-5% for each patient using Geneious® software version 8.1.5. HIV-1 drug resistance was inferred using the Calibrated Population Resistant (CPR) tool in HIV drug resistant database. Viral subtypes were determined using SCQUEL and RIP genotyping tools.
Results: Quality sequences were obtained for 253/257 (98.4%) of the patients. About 9.5% (24/253) of the patients harboured at least one surveillance drug resistance mutation (SDRM). The proportion of resistance mutations to NNRTI, PI, and NRTI were 8.3%, 1.4% and 0.8% respectively. A majority (15/24; 62.5%) of the patients harbouring SDRM were females, between the ages 21-66 years, with median CD4+ cell count of 212/µl (range:50-811) and median viral load of 20,863 copies/mL (range: 20-696 474). The most frequent SDRM was K103N (75%; 18/24), and of these 5/12 were in males (41.7%). K103N is associated with high-level reduction in Nevirapine (NVP) and Efavirenz (EFV) susceptibility. Other mutations observed included: NNRTI: V106M (3/24), K101 (1/24), P225H (3/24); NRTI: 1/24 of each of M41L, K65R, M184V, F77L; PI: G73S (1/24), D30N (2/24), L90M (1/24). All sequences were HIV-1 subtype C on the Pol gene, except one which was HIV-1 subtype G.
Conclusion and Recommendation: These observations from NGS analysis suggest that the study population, entering HIV treatment programmes in northern South Africa, harboured moderate levels of transmitted drug resistance mutations. Drug resistance surveillance studies may be needed to better understand resistance in the drug naïve population in the era of ’diagnose and treat.
Citation
@inproceedings{ogola2019,
author = {Ogola, Bixa and Matume, Nontokozo and Bessong, Pascal},
publisher = {20th International Conference on AIDS and STDs in Africa
(ICASA)},
title = {Prevalence and Diversity of {HIV} Drug Resistance Mutations
in Patients Entering Treatment Program in {Northern} {South}
{Africa}},
date = {2019-12-02},
langid = {en}
}