HIV-1 Subtypes B and C Unique Recombinant Forms (URFs) and Transmitted Drug Resistance Identified in the Western Cape Province, South Africa

South Africa has the largest worldwide HIV/AIDS population with 5.6 million people infected and at least 2 million people on antiretroviral therapy. The majority of these infections are caused by HIV-1 subtype C. Using genotyping methods we characterized HIV-1 subtypes of the gag p24 and pol PR and RT fragments, from a cohort of female participants in the Western Cape Province, South Africa. These participants were recruited as part of a study to assess the combined brain and behavioural effects of HIV and early childhood trauma. The partial HIV-1 gag and pol fragments of 84 participants were amplified by PCR and sequenced. Different online tools and manual phylogenetic analysis were used for HIV-1 subtyping. Online tools included: REGA HIV Subtyping tool version 3; Recombinant Identification Program (RIP); Context-based Modeling for Expeditious Typing (COMET); jumping profile Hidden Markov Models (jpHMM) webserver; and subtype classification using evolutionary algorithms (SCUEAL). HIV-1 subtype C predominates within the cohort with a prevalence of 93.8%. We also show, for the first time, the presence of circulating BC strains in at least 4.6% of our study cohort. In addition, we detected transmitted resistance associated mutations in 4.6% of analysed sequences. With tourism and migration rates to South Africa currently very high, we are detecting more and more HIV-1 URFs within our study populations. It is stil unclear what role these unique strains will play in terms of long term antiretroviral treatment and what challenges they will pose to vaccine development. Nevertheless, it remains vitally important to monitor the HIV-1 diversity in South Africa and worldwide as the face of the epidemic is continually changing.

南非是全球艾滋病（HIV/AIDS）感染人群规模最大的国家，现有560万感染者，且至少200万人正在接受抗逆转录病毒治疗（antiretroviral therapy）。该人群中绝大多数感染由HIV-1 C亚型（HIV-1 subtype C）所致。本研究针对南非西开普省的一组女性受试者队列，通过基因分型方法对其HIV-1的gag p24区（gag p24）、pol基因蛋白酶（PR）与逆转录酶（RT）片段的亚型进行了鉴定。该队列受试者是一项旨在评估HIV感染与早期童年创伤对大脑及行为联合影响的研究的招募对象。研究人员通过聚合酶链式反应（Polymerase Chain Reaction, PCR）扩增并测序了84名受试者的HIV-1 gag与pol基因部分片段。本研究采用多种在线工具与手动系统发育分析（phylogenetic analysis）方法完成HIV-1亚型分型，所用在线工具涵盖：REGA HIV分型工具v3（REGA HIV Subtyping tool version 3）、重组识别程序（Recombinant Identification Program, RIP）、快速分型上下文建模工具（Context-based Modeling for Expeditious Typing, COMET）、跳跃轮廓隐马尔可夫模型（jumping profile Hidden Markov Models, jpHMM）服务器，以及基于进化算法的亚型分类器（subtype classification using evolutionary algorithms, SCUEAL）。该队列中HIV-1 C亚型占绝对优势，流行率达93.8%。本研究还首次在至少4.6%的受试者队列中检出了流行的BC重组株（circulating BC strains）。此外，在4.6%的分析序列中检出了传播耐药相关突变（transmitted resistance associated mutations）。鉴于当前南非的旅游与移民规模居高不下，本研究人群中检出的HIV-1独特重组株（Unique Recombinant Forms, URFs）数量日益增多。目前尚不清楚这些独特重组株在长期抗逆转录病毒治疗中将发挥何种作用，也不确定它们会给疫苗研发带来哪些挑战。尽管如此，鉴于艾滋病疫情的流行态势持续演变，对南非乃至全球范围内的HIV-1基因多样性进行监测仍至关重要。