ABSTRACT
BACKGROUND: Global HIV-1 genetic diversity and evolution form a major challenge to treatment and prevention efforts. An increasing number of distinct HIV-1 recombinants have been identified worldwide, but their contribution to the global epidemic is unknown. We aimed to estimate the global and regional distribution of HIV-1 recombinant forms during 1990-2015. METHODS: We assembled a global HIV-1 molecular epidemiology database through a systematic literature review and a global survey. We searched the PubMed, Embase (Ovid), CINAHL (Ebscohost), and Global Health (Ovid) databases for HIV-1 subtyping studies published from Jan 1, 1990, to Dec 31, 2015. Unpublished original HIV-1 subtyping data were collected through a survey among experts in the field who were members of the WHO-UNAIDS Network for HIV Isolation and Characterisation. We included prevalence studies with HIV-1 subtyping data collected during 1990-2015. Countries were grouped into 14 regions and analyses were done for four time periods (1990-99, 2000-04, 2005-09, and 2010-15). The distribution of circulating recombinant forms (CRFs) and unique recombinant forms (URFs) in individual countries was weighted according to the UNAIDS estimates of the number of people living with HIV in each country to generate regional and global estimates of numbers and proportions of HIV-1 recombinants in each time period. The systematic review is registered with PROSPERO, CRD42017067164. FINDINGS: Our global data collection yielded an HIV-1 molecular epidemiology database of 383â519 samples from 116 countries in 1990-2015. We found that the proportion of recombinants increased over time, both globally and in most regions, reaching 22·8% (7â978â517 of 34â921â639) of global HIV-1 infections in 2010-15. Both the proportion and the number of distinct CRFs detected increased over time to 16·7% and 57 CRFs in 2010-15. The global and regional distribution of HIV-1 recombinants was diverse and evolved over time, and we found large regional variation in the numbers (0-44 CRFs), types (58 distinct CRFs), and proportions (0-80·5%) of HIV-1 recombinants. Globally, CRF02_AG was the most prevalent recombinant, accounting for 33·9% (2â701â364 of 7â978â517) of all recombinant infections in 2010-15. URFs accounted for 26·7% (2â131â450 of 7â978â517), CRF01_AE for 23·0% (1â838â433), and other CRFs for 16·4% (1â307â270) of all recombinant infections in 2010-15. Although other CRFs accounted for small proportions of infections globally (<1% each), they were prominent in regional epidemics, including in east and southeast Asia, west and central Africa, Middle East and north Africa, and eastern Europe and central Asia. In addition, in 2010-15, central Africa (21·3% [243â041 of 1â143â531]), west Africa (15·5% [838â476 of 5â419â010]), east Africa (12·6% [591â140 of 4â704â986]), and Latin America (9·6% [153â069 of 1â586â605]) had high proportions of URFs. INTERPRETATION: HIV-1 recombinants are increasingly prominent in global and regional HIV epidemics, which has important implications for the development of an HIV vaccine and the design of diagnostic, resistance, and viral load assays. Continued and improved surveillance of the global molecular epidemiology of HIV is crucial. FUNDING: None.
Subject(s)
HIV Infections/epidemiology , HIV Infections/virology , HIV-1/genetics , Reassortant Viruses/genetics , Genetic Variation , Genotype , Global Health/statistics & numerical data , HIV Infections/transmission , Humans , Molecular EpidemiologyABSTRACT
BACKGROUND: Global genetic diversity of HIV-1 is a major challenge to the development of HIV vaccines. We aimed to estimate the regional and global distribution of HIV-1 subtypes and recombinants during 1990-2015. METHODS: We searched PubMed, EMBASE (Ovid), CINAHL (Ebscohost), and Global Health (Ovid) for HIV-1 subtyping studies published between Jan 1, 1990, and Dec 31, 2015. We collected additional unpublished HIV-1 subtyping data through a global survey. We included prevalence studies with HIV-1 subtyping data collected during 1990-2015. We grouped countries into 14 regions and analysed data for four time periods (1990-99, 2000-04, 2005-09, and 2010-15). The distribution of HIV-1 subtypes, circulating recombinant forms (CRFs), and unique recombinant forms (URFs) in individual countries was weighted according to the UNAIDS estimates of the number of people living with HIV (PLHIV) in each country to generate regional and global estimates of HIV-1 diversity in each time period. The primary outcome was the number of samples designated as HIV-1 subtypes A, B, C, D, F, G, H, J, K, CRFs, and URFs. The systematic review is registered with PROSPERO, number CRD42017067164. FINDINGS: This systematic review and global survey yielded 2203 datasets with 383â519 samples from 116 countries in 1990-2015. Globally, subtype C accounted for 46·6% (16â280â897/34â921â639 of PLHIV) of all HIV-1 infections in 2010-15. Subtype B was responsible for 12·1% (4â235â299/34â921â639) of infections, followed by subtype A (10·3%; 3â587â003/34â921â639), CRF02_AG (7·7%; 2â705â110/34â921â639), CRF01_AE (5·3%; 1â840â982/34â921â639), subtype G (4·6%; 1â591â276/34â921â639), and subtype D (2·7%; 926â255/34â921â639). Subtypes F, H, J, and K combined accounted for 0·9% (311â332/34â921â639) of infections. Other CRFs accounted for 3·7% (1â309â082/34â921â639), bringing the proportion of all CRFs to 16·7% (5â844â113/34â921â639). URFs constituted 6·1% (2â134â405/34â921â639), resulting in recombinants accounting for 22·8% (7â978â517/34â921â639) of all global HIV-1 infections. The distribution of HIV-1 subtypes and recombinants changed over time in countries, regions, and globally. At a global level during 2005-15, subtype B increased, subtypes A and D were stable, and subtypes C and G and CRF02_AG decreased. CRF01_AE, other CRFs, and URFs increased, leading to a consistent increase in the global proportion of recombinants over time. INTERPRETATION: Global and regional HIV diversity is complex and evolving, and is a major challenge to HIV vaccine development. Surveillance of the global molecular epidemiology of HIV-1 remains crucial for the design, testing, and implementation of HIV vaccines. FUNDING: None.