A prospective cohort study was conducted to examine the relationship between vaginal colonization with lactobacilli, bacterial vaginosis (BV), and acquisition of human immunodeficiency virus type 1 (HIV-1) and sexually transmitted diseases in a population of sex workers in Mombasa, Kenya. In total, 657 HIV-1-seronegative women were enrolled and followed at monthly intervals. At baseline, only 26% of women were colonized with Lactobacillus species. During follow-up, absence of vaginal lactobacilli on culture was associated with an increased risk of acquiring HIV-1 infection (hazard ratio [HR], 2.0; 95% confidence interval [CI], 1.2-3.5) and gonorrhea (HR, 1.7; 95% CI, 1.1-2.6), after controlling for other identified risk factors in separate multivariate models. Presence of abnormal vaginal flora on Gram's stain was associated with increased risk of both HIV-1 acquisition (HR, 1.9; 95% CI, 1.1-3.1) and Trichomonas infection (HR, 1.8; 95% CI, 1.3-2.4). Treatment of BV and promotion of vaginal colonization with lactobacilli should be evaluated as potential interventions to reduce a woman's risk of acquiring HIV-1, gonorrhea, and trichomoniasis.

Janssen Vaccines & Prevention BV, National Institutes of Health, Ragon Institute of MGH, MIT and Harvard, Henry M Jackson Foundation for the Advancement of Military Medicine, US Department of Defense, and International AIDS Vaccine Initiative.

We conducted a prospective study among women in Mombasa, Kenya, to determine whether Trichomonas vaginalis infection was associated with an increased risk of human immunodeficiency virus type 1 (HIV-1) infection. At monthly follow-up visits, laboratory screening for HIV-1 and genital tract infections was conducted. Among 1335 HIV-1-seronegative women monitored for a median of 566 days, there were 806 incident T. vaginalis infections (23.6/100 person-years), and 265 women seroconverted to HIV-1 (7.7/100 person-years). Trichomoniasis was associated with a 1.52-fold (95% confidence interval, 1.04-2.24-fold) increased risk of HIV-1 acquisition after adjustment for potential confounding factors. Treatment and prevention of T. vaginalis infection could reduce HIV-1 risk in women.

Designing an effective human immunodeficiency virus type 1 (HIV-1) vaccine will rely on understanding which variants, from among the myriad of circulating HIV-1 strains, are most commonly transmitted and determining whether such variants have an Achilles heel. Here we show that heterosexually acquired subtype A HIV-1 envelopes have signature sequences that include shorter V1-V2 loop sequences and fewer predicted N-linked glycosylation sites relative to the overall population of circulating variants. In contrast, recently transmitted subtype B variants did not, and this was true for cases where the major risk factor was homosexual contact, as well as for cases where it was heterosexual contact. This suggests that selection during HIV-1 transmission may vary depending on the infecting subtype. There was evidence from 23 subtype A-infected women for whom there was longitudinal data that those who were infected with viruses with fewer potential N-linked glycosylation sites in V1-V2 had lower viral set point levels. Thus, our study also suggests that the extent of glycosylation in the infecting virus could impact disease progression.Studies in the simian immunodeficiency virus (SIV)/macaque model of AIDS have shown that the viruses that evolve over the course of disease are selected in part because they increase the number and/or vary the position of the carbohydrates to shield them from the host antibody response (1, 15). Subsequent studies indicate that a similar evolutionary process may occur in the human immunodeficiency virus type 1 (HIV-1) envelope during both simian/human immunodeficiency virus infection in macaques (2) and HIV-1 infection in humans (17). A recent study of eight individuals infected with subtype C HIV-1 suggested that there may be counterselection at transmission against variants with long hypervariable loops and relatively large numbers of potential N-linked glycosylation sites, which are predicted to have a more recessed receptor-binding domain (4). The transmitted subtype C HIV-1s had signature sequence characteristics, which included shorter envelope variable loop domains and fewer potential N-linked glycosylation sites (PNGS) (4). Because the study was limited to a small number of cases, all of one subtype, it is unclear whether transmission of viruses with these characteristics is typical, a point that is of importance for designing globally effective vaccines and other interventions to block transmitted viruses.We examined HIV-1 sequences within a median of 70 days (interquartile range [IQR], 49 to 161) post negative serology (PNS) from 27 women and eight men from Kenya who acquired subtype A HIV-1 through heterosexual transmission (8, 9, 13; unpublished data). The days PNS was defined as the time from the last HIV-1-negative serological test to when the sample used to obtain sequences was taken. The sequences were compared to subtype A sequences in the Los Alamos database to determine if they differed in V1-V2 length or number of PNGS. The Los Alamos database includes sequences from su...