Using phylogeography to characterize the origins of the HIV-1 subtype F epidemic in Romania

Background: During the late 1980s and early 1990s, an estimated 10,000 Romanian children were infected with HIV-1 subtype F nosocomially through contaminated needles and blood transfusions. However, the geographic source and origins of this epidemic remain unclear.

Methods: Here we used phylogenetic inference and "relaxed" molecular clock dating analysis to further characterize the Romanian HIV-1 subtype F epidemic.

Results: These analyses revealed a major lineage of Romanian HIV sequences consisting nearly entirely of virus sampled from adolescents and children and a distinct cluster that included a much higher ratio of adult sequences. Divergence time estimates inferred the time of most recent common ancestor of subtype F1 sequences to be 1973 (1966-1980) and for all Angolan sequences to 1975 (1968-1980). The most common ancestor of the Romanian sequences was dated to 1978 (1972-1983) with pediatric and adolescent sequences interspersed throughout the lineage. The phylogenetic structure of the entire subtype F epidemic suggests that multiple introductions of subtype F into Romania occurred either from the Angolan epidemic or from more distant ancestors. Since the historical records note that the Romanian pediatric epidemic did not begin until the late 1980s, the inferred time of most recent common ancestor of the Romanian lineage of 1978 suggests that there were multiple introductions of subtype F occurred into the pediatric population from HIV already circulating in Romania.

Conclusions: Analysis of the subtype F HIV-1 epidemic in an historical context allows for a deeper appreciation of how the HIV pandemic has been influenced by socio-political events.