Association between heterosexual exposure and infection with B/C and C subtype HIV-1 in Southern Brazil

Background: Subtype C is the predominant global strain of HIV-1, in many countries overtaking a preexisting epidemic strain. Reasons for this may include founder effect, segregation of subtypes within non-overlapping sociodemographic groups, or biological properties favoring heterosexual transmission of subtype C. It has been difficult to distinguish among these in previously studied settings. Projeto AMPLIAR is studying an explosive subtype C epidemic in the southern Brazilian state of Rio Grande do Sul.
Methods: Socio-demographic and risk behavior data were collected prior to counseling from consenting VCT clients ≥ 16 years old at 4 testing sites. HIV status was determined by a reference standard including a 4th generation EIA, HIV NAAT, and follow-up serology (if initially positive). Population pol sequences were analyzed using multiple subtyping tools (Rega,RIP3.0,NCBI,STAR).
Results: From 10/2004 through 11/2008 4584 clients were evaluated, with 731 (15.9%) HIV+. Of these, 333 were subtyped (35% C, 34% B/C recombinants, 24% B, and 7% F/F recombinants). The 113 B/C viruses showed 62 distinct patterns of recombination: 44 were unique forms, 5 were CRF31, and 64 fell into 17 novel groups. Subtyping and behavioral data were available on 221 participants. Odds of subtype C vs. B infection were much higher in heterosexuals, when compared to MSM (AOR 4.7 (1.6-13.8)), adjusting for sexual exposure, age, schooling, and race. Adjusted odds of infection with BC recombinants vs. B were also higher among heterosexuals than MSM (AOR 3.4 (1.07-11).
Conclusions: In a region with co-circulating subtypes, C-containing virus accounted for 69% of infections. The prevalence and diversity of BC recombinants suggests extensive mixing, yet both pure C and C-containing viruses are strongly and consistently associated with heterosexual exposure. This association is not explained by sociodemographic factors. These observations suggest a biological contribution to the transmission efficiency of C-containing virus, although a contributing founder effect cannot be ruled out.

O. Bacon1, R. da Silva de Souza2, S. Frost3, R. Diaz4, S. Pillai5, L. Motta2, R.D. Sperhacke2, E. Charlesbois5, F. Hecht5, C. Pilcher5
1Univ. California San Francisco, Medicine/Positive Health Program, San Francisco, United States, 2Universidade do Caxias do Sul, Caxias do Sul, Brazil, 3Cambridge University, Cambridge, United Kingdom, 4Universidade Federal do Sao Paulo, Sao Paulo, Brazil, 5University of California, San Francisco, United States