Molecular Epidemiology of Human Immunodeficiency Virus Type 1 Transmission in a Heterosexual Cohort of Discordant Couples in Zambia

Abstract

Most human immunodeficiency virus type 1 (HIV-1) transmissions in sub-Saharan Africa are believed to occur between married adults who are discordant for their HIV-1 infection status; however, no studies to date have investigated the molecular epidemiology of such transmission events. Here we report the genetic characterization of HIV-1 strains from 149 transmission pairs that were identified prospectively in a cohort of discordant couples in Lusaka, Zambia. Subgenomic gag, gp120, gp41, and/or long terminal repeat regions were amplified by PCR analysis of uncultured blood samples from both partners and sequenced without interim cloning. Pairwise genetic distances were calculated for the regions analyzed and compared to those of subtypespecific reference sequences as well as local controls. Sequence relationships were also examined by phylogenetic tree analysis. By these approaches, epidemiological linkage was established for the majority of transmission pairs. Viruses from 129 of the 149 couples (87%) were very closely related and clustered together in phylogenetic trees in a statistically highly significant manner. In contrast, viruses from 20 of the 149 couples (13%) were only distantly related in two independent genomic regions, thus ruling out transmission between the two partners. The great majority (95%) of transmitted viruses were of subtype C origin, although representatives of subtypes A, D, G, and J were also identified. There was no evidence for extensive transmission networks within the cohort, although two phylogenetic subclusters of viruses infecting two couples each were identified. Taken together, these data indicate that molecular epidemiological analyses of presumed transmission pairs are both feasible and required to determine behavioral, virological, and immunological correlates of heterosexual transmission in sub-Saharan Africa with a high level of accuracy.

Genetic Diversity of HIV Type 1 in Likasi, Southeast of the Democratic Republic of Congo

“…[2][3][4][5][6][7] The proportion of CRF02_AG among subtype A strains based on env sequences decreases from west to central Africa, with an absence of CRF02_AG in the Democratic Republic of Congo (DRC). 2,8,9 The profile of HIV-1 endemic in DRC, such as high number of cocirculating HIV-1 subtypes, possible recombinant viruses, and unclassified strains, is consistent with that of an old and mature epidemic of HIV-1. 5 The DRC is bordered on the southeast by Zambia.…”

Escape and Compensation from Early HLA-B57-Mediated Cytotoxic T-Lymphocyte Pressure on Human Immunodeficiency Virus Type 1 Gag Alter Capsid Interactions with Cyclophilin A

“…2 were obtained from a cohort of 88 epidemiologically linked subtype C heterosexual transmission pairs enrolled in a discordant couple cohort in Lusaka, Zambia. Details of this cohort have been described previously (25,63). The set point viral load in donors was determined by repeated longitudinal testing to ensure values were stable within 0.3 logs.…”

“…Epidemiologically linked transmission pairs were identified as described previously during follow-up of a discordant couple cohort at the Zambia Emory HIV Research Project (25,63). Couples were counseled and provided condoms at each 3-month return visit.…”

Role of donor genital tract HIV-1 diversity in the transmission bottleneck

“…Viral DNA was used to establish epidemiological linkage and Env subtype as previously described (9,10,42). cDNA synthesis and SGA of the env gene from PB, PL, and genital fluids (SW, CA, and CF) was performed using end pointlimiting dilution nested PCR to produce full-length gp160 (9-11, 14, 15, 18, 43).…”