Molecular epidemiology of HIV-1 transmission in a cohort of HIV-1 concordant heterosexual couples from Dakar, Senegal

Abstract

Background: A large number of HIV-1 infections in Africa occur in married couples. The predominant direction of intracouple transmission and the principal external origins of infection remain important issues of debate.

Methods: We investigated HIV-1 transmission in 46 HIV-1 concordant positive couples from Dakar, Senegal. Intracouple transmission was confirmed by maximum-likelihood phylogenetic analysis and pairwise distance comparisons of HIV-1 env gp41 sequences from both partners. Standardized interview data were used to deduce the direction as well as the external sources of the intracouple transmissions.

Results: Conservative molecular analyses showed linked viruses in 34 (74%) couples, unlinked viruses in 6 (13%) couples, and indeterminate results for 6 (13%) couples. The interview data corresponded completely with the molecular analyses: all linked couples reported internal transmission and all unlinked couples reported external sources of infection. The majority of linked couples (93%) reported the husband as internal source of infection. These husbands most frequently (82%) reported an occasional sexual relationship as external source of infection. Pairwise comparisons of the CD4 count, antiretroviral therapy status, and the proportion of gp41 ambiguous base pairs within transmission pairs correlated with the reported order of infection events.

Conclusions: In this suburban Senegalese population, a majority of HIV-1 concordant couples showed linked HIV-1 transmission with the husband as likely index partner. Our data emphasize the risk of married women for acquiring HIV-1 as a result of the occasional sexual relationships of their husbands.

Figure 1. Numbers of couples analyzed in this study.

Flow chart showing the numbers of couples that were screened and analyzed in the molecular and epidemiological parts of the study. ^aThese include HIV-2 discordant, HIV-2 concordant positive, and mixed HIV-1/2 concordant positive couples, see text for details.

Figure 2. Molecular analysis of HIV-1 transmission in 46 HIV-1 concordant couples.

(A) Maximum-likelihood phylogenetic tree. All individual sequences are labeled by their couple number followed by M (male partner) or F (female partner). Female partners in polygamous partnerships are labeled as F1 and F2. Bootstrap values are calculated from 500 replicates; values of 50% or more are shown. Sequences from partners of the same couple are colored in blue if they cluster with a bootstrap value of 80% or more; in green if they cluster with a bootstrap value below 80%; in red if they are on separate branches of the tree. HIV-1 subtypes are shown on the main branches of the tree, HIV-1 reference sequences are omitted. The scale represents the maximum-likelihood genetic distance. (B) Maximum-likelihood genetic distances. Distance values between sequences of male and female partners of the same couple are shown. Bars correspond to the pairs of clustered or non-clustered sequences as they appear in the phylogenetic tree in panel A. Distance values between pairs of non-clustered sequences are shown for only one of the two sequences; the other sequence is labeled “id.” (idem). The dotted line represents the distance cut-off value for linked sequences which is set at 0.04.