Nuffield Department of Women's and Reproductive Health, University of Oxford, Women's Centre, John Radcliffe Hospital, Oxford, United Kingdom
Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
J Virol. 2020 Dec 22;95(2). doi: 10.1128/JVI.01580-20.
The global diversity of HIV forms a major challenge to the development of an HIV vaccine, as well as diagnostic, drug resistance, and viral load assays, which are essential to reaching the UNAIDS 90:90:90 targets. We sought to determine country level HIV-1 diversity globally between 1990 and 2015. We assembled a global HIV-1 molecular epidemiology database through a systematic literature search and a global survey. We searched PubMed, EMBASE (Ovid), CINAHL (Ebscohost), and Global Health (Ovid) for HIV-1 subtyping studies published from 1 January 1990 to 31 December 2015. We collected additional unpublished data through a global survey of experts. Prevalence studies with original HIV-1 subtyping data collected between 1990 and 2015 were included. This resulted in a database with 383,519 subtyped HIV-1 samples from 116 countries over four time periods (1990 to 1999, 2000 to 2004, 2005 to 2009, and 2010 to 2015). We analyzed country-specific numbers of distinct HIV-1 subtypes, circulating recombinant forms (CRFs), and unique recombinant forms (URFs) in each time period. We also analyzed country-specific proportions of infections due to HIV-1 recombinants, CRFs, and URFs and calculated the Shannon diversity index for each country. Finally, we analyzed global temporal trends in each of these measures of HIV-1 diversity. We found extremely wide variation in complexity of country level HIV diversity around the world. Central African countries such as Chad, Democratic Republic of the Congo, Angola, and Republic of the Congo have the most diverse HIV epidemics. The number of distinct HIV-1 subtypes and recombinants was greatest in Western Europe (Spain and France) and North America (United States) (up to 39 distinct HIV-1 variants in Spain). The proportion of HIV-1 infections due to recombinants was highest in Southeast Asia (>95% of infections in Viet Nam, Cambodia, and Thailand), China, and West and Central Africa, mainly due to high proportions of CRF01_AE and CRF02_AG. Other CRFs played major roles (>75% of HIV-1 infections) in Estonia (CRF06_cpx), Iran (CRF35_AD), and Algeria (CRF06_cpx). The highest proportions of URFs (>30%) were found in Myanmar, Republic of the Congo, and Argentina. Global temporal analysis showed consistent increases over time in country level numbers of distinct HIV-1 variants and proportions of CRFs and URFs, leading to increases in country level HIV-1 diversity. Our study provides epidemiological evidence that the HIV pandemic is diversifying at country level and highlights the increasing challenge to prevention and treatment efforts. HIV-1 molecular epidemiological surveillance needs to be continued and improved. This is the first study to analyze global country level HIV-1 diversity from 1990 to 2015. We found extremely wide variation in complexity of country level HIV diversity around the world. Central African countries have the most diverse HIV epidemics. The number of distinct HIV-1 subtypes and recombinants was greatest in Western Europe and North America. The proportion of HIV-1 infections due to recombinants was highest in South-East Asia, China, and West and Central Africa. The highest proportions of URFs were found in Myanmar, Republic of the Congo, and Argentina. Our study provides epidemiological evidence that the HIV pandemic is diversifying at country level and highlights the increasing challenge to HIV vaccine development and diagnostic, drug resistance, and viral load assays.
全球 HIV 形式的多样性对 HIV 疫苗的开发以及诊断、耐药性和病毒载量检测构成了重大挑战,这些都是实现艾滋病署 90-90-90 目标所必需的。我们旨在确定全球 HIV-1 多样性在 1990 年至 2015 年之间的变化情况。我们通过系统文献检索和全球调查,建立了一个全球 HIV-1 分子流行病学数据库。我们在 PubMed、EMBASE(Ovid)、CINAHL(Ebscohost)和 Global Health(Ovid)中搜索了从 1990 年 1 月 1 日至 2015 年 12 月 31 日发表的 HIV-1 亚型研究。我们通过对专家的全球调查收集了额外的未发表数据。本研究纳入了在 1990 年至 2015 年期间收集的原始 HIV-1 亚型数据的患病率研究。这使得数据库中包含了来自 116 个国家的 383519 份 HIV-1 亚型样本,分为四个时间段(1990 年至 1999 年、2000 年至 2004 年、2005 年至 2009 年和 2010 年至 2015 年)。我们分析了每个时间段内每个国家独特的 HIV-1 亚型、循环重组形式(CRF)和独特重组形式(URF)的数量。我们还分析了每个国家因 HIV-1 重组、CRF 和 URF 引起的感染比例,并计算了每个国家的香农多样性指数。最后,我们分析了这些 HIV-1 多样性衡量标准在每个国家的全球时间趋势。我们发现,全球各国 HIV 多样性的复杂程度存在极大差异。乍得、刚果民主共和国、安哥拉和刚果共和国等中非国家的 HIV 流行情况最为复杂。HIV-1 亚型和重组数量最多的是西欧(西班牙和法国)和北美(美国)(西班牙有多达 39 种不同的 HIV-1 变体)。HIV-1 感染因重组引起的比例最高的是东南亚(越南、柬埔寨和泰国的感染比例超过 95%)、中国和西非和中非,主要是由于 CRF01_AE 和 CRF02_AG 的比例较高。其他重组(超过 75%的 HIV-1 感染)在爱沙尼亚(CRF06_cpx)、伊朗(CRF35_AD)和阿尔及利亚(CRF06_cpx)中发挥了主要作用。URF 比例最高(超过 30%)的国家有缅甸、刚果共和国和阿根廷。全球时间分析显示,随着时间的推移,国家一级独特的 HIV-1 变体数量和 CRF 和 URF 的比例持续增加,导致国家一级 HIV-1 多样性增加。我们的研究提供了流行病学证据,表明 HIV 大流行在国家一级正在多样化,并突出了对预防和治疗工作的日益挑战。需要继续和改进 HIV-1 分子流行病学监测。这是第一项分析 1990 年至 2015 年全球 HIV-1 多样性的研究。我们发现,全球各国 HIV 多样性的复杂程度存在极大差异。乍得、刚果民主共和国、安哥拉和刚果共和国等中非国家的 HIV 流行情况最为复杂。HIV-1 亚型和重组数量最多的是西欧(西班牙和法国)和北美(美国)。HIV-1 感染因重组引起的比例最高的是东南亚、中国和西非和中非,主要是由于 CRF01_AE 和 CRF02_AG 的比例较高。URF 比例最高(超过 30%)的国家有缅甸、刚果共和国和阿根廷。我们的研究提供了流行病学证据,表明 HIV 大流行在国家一级正在多样化,并突出了对 HIV 疫苗开发以及诊断、耐药性和病毒载量检测的日益挑战。