Molecular epidemiology of HIV type 1 CRF02_AG in Cameroon and African patients living in Italy

Abstract

HIV-1 CRF02_AG accounts for >50% of infected individuals in Cameroon. CRF02_AG prevalence has been increasing both in Africa and Europe, particularly in Italy because of migrations from the sub-Saharan region. This study investigated the molecular epidemiology of CRF02_AG in Cameroon by employing Bayesian phylodynamics and analyzed the relationship between HIV-1 CRF02_AG isolates circulating in Italy and those prevalent in Africa to understand the link between the two epidemics. Among 291 Cameroonian reverse transcriptase sequences analyzed, about 70% clustered within three distinct clades, two of which shared a most recent common ancestor, all related to sequences from Western Africa. The major Cameroonian clades emerged during the mid-1970s and slowly spread during the next 30 years. Little or no geographic structure was detected within these clades. One of the major driving forces of the epidemic was likely the high accessibility between locations in Southern Cameroon contributing to the mobility of the population. The remaining Cameroonian sequences and the new strains isolated from Italian patients were interspersed mainly within West and Central African sequences in the tree, indicating a continuous exchange of CRF02_AG viral strains between Cameroon and other African countries, as well as multiple independent introductions in the Italian population. The evaluation of the spread of CRF02_AG may provide significant insight about the future dynamics of the Italian and European epidemic.

FIG. 1.

Maximum likelihood (ML) phylogenetic analysis of HIV-1 CRF02_AG. The ML tree includes 824 strains of African and Italian origin. The color of a tip branch represents the geographic region from where the strain originated, according to the legend given in the figure. Branch lengths were scaled in nucleotide substitutions per site as indicated by the bar at the bottom. Approximate likelihood-ratio test (aLRT) SH-like p-values for supported clades (p>0.75) are also indicated. For display purposes, the three supported Cameroon monophyletic clades, 1, 2, and 3, have been collapsed and colored in purple, yellow, and blue, respectively. A tree with fully labeled tips is given in Supplementary Fig. S1.

FIG. 2.

Marginal density of evolutionary rate estimates for each Cameroon CRF02_AG monophyletic clade. Distribution of mean evolutionary rate estimates (x-axis) from 10,000 Markov chain Monte Carlo (MCMC) sampled trees (minus 10% burn-in). The time of the most recent common ancestor (TMRCA) with 95% high density posterior (95% HPD) intervals is also indicated.

FIG. 3.

Phylogeographic structure of Cameroon CRF02_AG clades. Distribution of observed migrations (x-axis) in 10,000 random trees generated using the sequences of each of the three well-supported monophyletic CRF02_AG Cameroon clades highlighted in Fig. 1. The arrow indicates the number of migrations observed in the Bayesian maximum clade credibility (MCC) tree including only the sequences from a specific clade (MCC trees are given in Supplementary Fig. S3). (A) Cameroon clade 1 sequences. (B) Cameroon clade 2 sequences. (C) Cameroon clade 3 sequences.

FIG. 4.

CRF02_AG geographic distribution and Cameroon accessibility map. (A) On the left a map of Africa is displayed with the countries involved in the CRF02_AG flow to Cameroon, and an expanded Cameroon map is shown to the right. Circles indicate the sampling locations of Cameroonian sequences. Strains clustering within clade 1, 2, 3 or intermixed in the tree are represented according to the legend on the right top of the map. (B) Cameroon accessibility map. The gray gradient of colors, according to the color bar in the figure, indicates the estimated travel time to the nearest city of population >100,000 people, with white at one extreme indicating low travel times (<30 min) and dark gray at the other extreme indicating long travel times (>10 h).

FIG. 5.

Citizens from Cameroon and other African countries (bordering and not bordering Cameroon) involved in the spread of CRF02_AG and residing in Italy: demographic balance over the years 2002–2008. For each year, the demographic balance is updated to December 31. N: Overall number of immigrants residing in Italy over the years 2002–2008.