Background:  Candidate HIV-1 vaccines are being evaluated in East Africa and Thailand, where inter-subtype recombinant forms often constitute a substantial fraction of the circulating strains. Dual infection, more common in high-risk, multiply exposed individuals, is thought to be the proximal source of new recombinants. Most recombinant strains do not appear to establish population-level spread; the majority of identified recombinants are unique, isolated only from a single individual.  Factors that lead to the emergence of circulating recombinant forms (CRF) are incompletely understood. Our objective was to analyze the structure and relationships of inter-subtype recombinant HIV-1 from different risk groups in Asia and East Africa, and identify factors leading to emergent CRF.

Methods:  Virtually complete genome sequences representing 125 inter-subtype recombinant strains, mostly collected between 1996 and 2005, were tabulated with respect to component subtypes and breakpoints. Newly developed software (Breakpoint Blast) was used to evaluate the frequency of breakpoints across the genome and to identify breakpoints common to two or more strains. The relationship of strain complexity and shared breakpoints to date of isolation, geographic region, and risk group was evaluated.

Results:  From East Africa, we collected 66 recombinant strains exclusively from heterosexual or perinatal transmission, and, from Asia, 59 about half from injecting drug users (IDU) and half from heterosexual transmission, were available for analysis. In Asia, strains from IDU shared many more breakpoints than those from heterosexual contact.  CRF maintained their structure during wide geographic spread but also shared breakpoints with other recombinant strains, composed of the same subtypes, in their respective geographic regions.

Conclusions:  Recombinant strains reflect the social networks in which they spread. In multiply exposed, high-risk groups, repeated cycles of dual infection and recombination leads to a dynamic network of complex and inter-related recombinants. CRF may emerge when strains from high-risk groups enter larger, but lower-risk, heterosexual networks, where lower dual infection rates lead to a stabilization of their structure. In vaccine trials, particularly those in high-risk groups, the possibility exists that vaccinees may be exposed to multiple HIV-1 strains in a single transmission event, and to related but non-identical recombinant strains in the population.