HIV-1 molecular epidemiology in Guinea-Bissau, West Africa: origin, demography and migrations

Abstract

The HIV-1 epidemic in West Africa has been dominated by subtype A and the recombinant form CRF02_AG. Little is known about the origins and the evolutionary history of HIV-1 in this region. We employed Maximum likelihood and Bayesian methods in combination with temporal and spatial information to reconstruct the HIV-1 subtype distribution, demographic history and migration patterns over time in Guinea-Bissau, West Africa. We found that CRF02_AG and subsubtype A3 were the dominant forms of HIV-1 in Guinea-Bissau and that they were introduced into the country on at least six different occasions between 1976 and 1981. These estimates also corresponded well with the first reported HIV-1 cases in Guinea-Bissau. Migration analyses suggested that (1) the HIV-1 epidemic started in the capital Bissau and then dispersed into more rural areas, and (2) the epidemic in Guinea-Bissau was connected to both Cameroon and Mali. This is the first study that describes the HIV-1 molecular epidemiology in a West African country by combining the results of subtype distribution with analyses of epidemic origin and epidemiological linkage between locations. The multiple introductions of HIV-1 into Guinea-Bissau, during a short time-period of five years, coincided with and were likely influenced by the major immigration wave into the country that followed the end of the independence war (1963-1974).

Figure 1. a–b. Determination of Guinea-Bissau-specific clusters in HIV-1 CRF02_AG and subsubtype A3 phylogenies.

Maximum-likelihood trees were reconstructed based on the sequences from Guinea-Bissau together with reference sequences (A. CRF02_AG and B. subsubtype A3). The scale bar at the bottom of each tree represents 0.01 nucleotide substitutions per site. Asterisks along branches represent significant monophyletic clusters (**: Zero-branch-length test p-values <0.001, and posterior probabilities >95% in corresponding Bayesian analysis. *: Zero-branch-length test p-values <0.01, and posterior probabilities >90%). Statistically supported clusters are numbered according to appearance in tree and the corresponding tMRCA are marked with filled circles (red circles  =  Guinea-Bissau-specific tMRCAs, and black circles  =  the tMRCA of the CRF02_AG or subsubtype A3). The colours represent the country or geographic region representing the origin of each tip in the phylogeny.

Figure 2. a–d. Bayesian skyline plots for the CRF02_AG and subsubtype A3 epidemics.

Non-parametric median estimates of the number of effective infections over time for a. the CRF02_AG Guinea-Bissau cluster 2, b. the CRF02_AG epidemic in West Africa, c. the subsubtype A3 Guinea-Bissau cluster 1, and d. the subsubtype A3 epidemic in West Africa. All plots were based on the relaxed clock assumption. The grey lines represent the upper and lower 95% highest posterior density estimates. The pink area highlights the decade following the time period (1976–1981) of the estimated HIV-1 introductions into Guinea-Bissau.

Figure 3. Net migration rates over 5-year intervals.

Mean number of immigrating and emigrating people per 1000 individuals over different 5-year intervals from 1950 to 2010 for Guinea-Bissau and neighbouring countries (Guinea, Mali, Senegal, and The Gambia). The pink area highlights the time period of the estimated HIV-1 introductions into Guinea-Bissau. Data were obtained from the United Nations World Population Prospects (United Nations Population Division, 2010) .

Figure 4. Temporal dynamics of spatial HIV-1 CRF02_AG diffusion within Guinea-Bissau.

Snapshots of the HIV-1 CRF02_AG dispersal pattern within Guinea-Bissau. Lines between locations represent branches in the maximum clade credibility tree (MCC) along which well-supported location transitions occurs. The diffusion process was visualized in Google Earth (http://earth.google.com).

Figure 5. Temporal dynamics of spatial HIV-1 subsubtype A3 diffusion within Guinea-Bissau.

Snapshots of the HIV-1 subsubtype A3 dispersal pattern within Guinea-Bissau. Lines between locations represent branches in the maximum clade credibility tree (MCC) along which well-supported location transitions occurs. The diffusion process was visualized in Google Earth (http://earth.google.com).

Figure 6. Temporal dynamics of spatial HIV-1 CRF02_AG diffusion between Guinea-Bissau and other African countries.

Snapshots of the HIV-1 CRF02_AG dispersal pattern between Guinea-Bissau and other African countries. Lines between locations represent branches in the maximum clade credibility tree (MCC) along which well-supported location transitions occurs. The diffusion process was visualized in Google Earth (http://earth.google.com).