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Journal of Virology, January 2002, p. 397-405, Vol. 76, No. 1
0022-538X/01/$04.00+0     DOI: 10.1128/JVI.76.1.397-405.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

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

Stanley A. Trask,1 Cynthia A. Derdeyn,2 Ulgen Fideli,3 Yalu Chen,1 Sreelatha Meleth,1 Francis Kasolo,4 Rosemary Musonda,5 Eric Hunter,2 Feng Gao,1 Susan Allen,3 and Beatrice H. Hahn1,2*

Departments of Medicine,1 Microbiology, School of Medicine,2 Department of Epidemiology and International Health, School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama 35294,3 Department of Pathology and Microbiology, University Teaching Hospital, Lusaka,4 Tropical Disease Research Center, Ndola, Zambia5

Received 24 July 2001/ Accepted 24 September 2001

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 subtype-specific 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.

* Corresponding author. Mailing address: Department of Medicine, University of Alabama at Birmingham, 720 20th Street South, KAUL 816, Birmingham, AL 35294. Phone: (205) 934-0412. Fax: (205) 934-1580. E-mail: bhahn{at}uab.edu.

Journal of Virology, January 2002, p. 397-405, Vol. 76, No. 1
0022-538X/01/$04.00+0     DOI: 10.1128/JVI.76.1.397-405.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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