Timing of the HIV-1 subtype C epidemic in Ethiopia based on early virus strains and subsequent virus diversification

Objective: To trace the introduction of HIV-1 subtype C into Ethiopia based on virus diversification during the epidemic. Design: A set of 474 serum samples obtained in Ethiopia in 1982-1985 was te sted for HIV-1. HIV-1 env gp120 V3 and gag or pot regions were sequenced an d analysed together with sequences from later stages of the epidemic. Results: None of 98 samples from 1982-1983, one of 193 samples from 1984, a nd one of 183 samples from 1985 were HIV-1 positive. Phylogenetic analysis of virus sequences from positive samples revealed that they belong to the E thiopian C, and not the C ', cluster. Analysis of 81 Ethiopian C V3 sequenc es from 1984-1997 revealed that the consensus sequence of the Ethiopian epi demic has been stable over time. Both the 1984 and 1985 V3 sequences, in co ntrast with three out of 27 (11%) of the 1988 and none out of 51 of the 199 2-1997 sequences, had no synonymous substitutions compared to the reconstru cted common ancestor of the Ethiopian C viruses. A highly significant corre lation between sampling years of the V3 sequences and their synonymous dist ances to the common ancestor was demonstrated. Conclusions: The increasing genetic heterogeneity together with stable cons ensus sequence of the Ethiopian HIV-1 C population demonstrates that evolut ion of the virus population is characterized by an unbiased expansion aroun d a stationary consensus. Based on the rate of synonymous diversification o f HIV-1 strains within the Ethiopian population, we were able to estimate 1 983 (95% confidence interval, 1980-1984) as the year of HIV-1 C introductio n into Ethiopia. (C) 2001 Lippincott Williams & Wilkins.