Molecular epidemiology and transmission dynamics of the HIV-1 epidemic in Ethiopia: epidemic decline coincided with behavioral interventions before ART scale-up

BACKGROUND: Ethiopia is one of the sub-Saharan countries hit hard by the HIV epidemic. Previous studies have shown that subtype C dominates the Ethiopian HIV-1 epidemic, but the evolutionary and temporal dynamics of HIV-1 in Ethiopia have not been closely scrutinized. Understanding the evolutionary and epidemiological pattern of HIV is vital to monitor the spread, evaluate and implement HIV prevention strategies. - METHODS: We analyzed 1,276 Ethiopian HIV-1 subtype C polymerase (pol sequences), including 144 newly generated sequences, collected from different parts of the country from 1986 to 2017. We employed state-of-art maximum likelihood and Bayesian phylodynamic analyses to comprehensively describe the evolutionary dynamics of the HIV-1 epidemic in Ethiopia. We used Bayesian phylodynamic models to estimate the dynamics of the effective population size (Ne) and reproductive numbers (Re) through time for the HIV epidemic in Ethiopia. - RESULTS: Our analysis revealed that the Ethiopian HIV-1 epidemic originated from two independent introductions at the beginning of the 1970s and 1980s from eastern and southern African countries, respectively, followed by epidemic growth reaching its maximum in the early 1990s. We identified three large clusters with a majority of Ethiopian sequences. Phylodynamic analyses revealed that all three clusters were characterized by high transmission rates during the early epidemic, followed by a decline in HIV-1 transmissions after 1990. Re was high (4–6) during the earlier time of the epidemic but dropped significantly and remained low (Re 1) after the mid-1990. Similarly, with an expected shift in time, the effective population size (Ne) steadily increased until the beginning of 2000, followed by a decline and stabilization until recent years. The phylodynamic analyses corroborated the modeled UNAIDS incidence and prevalence estimates. - CONCLUSIONS: The rapid decline in the HIV epidemic took place a decade before introducing antiretroviral therapy in Ethiopia and coincided with early behavioral, preventive, and awareness interventions implemented in the country. Our findings highlight the importance of behavioral interventions and antiretroviral therapy scale-up to halt and maintain HIV transmissions at low levels (Re 1). The phylodynamic analyses provide epidemiological insights not directly available using standard surveillance and may inform the adjustment of public health strategies in HIV prevention in Ethiopia.Introduction Materials and methods - Baseline HIV-1 Drug Resistance Survey - Study Population and Sequence Dataset - HIV-1 Subtyping - Maximum Likelihood Phylogenetic Analyses - Analysis of Transmission Clusters - Estimating Temporal Signal - Estimating Viral Phylodynamic History - Ethical Approval Results - Study Population and Initial Phylogenetic Analysis - Transmission Cluster Analysis - Evolutionary Rates and Dates of HIV-1 Subtype C in Ethiopia - Temporal Dynamics of Viral Transmission Discussio