The HIV-1 epidemic in Ethiopia – transmission patterns, antiretroviral drug resistance and treatment outcomes

Ethiopia is among sub-Saharan country that has been hard hit by the HIV epidemic. Although previous studies have indicated that the epidemic is dominated by subtype C, the evolutionary and temporal dynamics of HIV-1 in Ethiopia are not well scrutinized. It is crucial to understand the epidemiological and evolutionary patterns of HIV in order to monitor its spread, evaluate, and implement HIV prevention strategies. Ethiopia, like many low-income countries, has sparse and incomplete HIV epidemiological data, making HIV epidemic surveillance difficult. However, with the increased availability of HIV genetic sequencing data and the development of phylogenetic and phylodynamic tools, molecular epidemiology analysis can now be used to describe the transmission dynamics and evolutionary history of HIV. In this PhD thesis, we used state-of-art phylogenetic and phylodynamic methods, including both Bayesian coalescent and birth–death models to estimate the dynamics of the effective population size (Ne) and reproductive numbers (Re) through time for the HIV-1 epidemic in Ethiopia. In our study, we showed that the HIV epidemic in Ethiopia originated from two independent introduction in the mid-1970s and mid-1980s. Furthermore, we showed that the Ethiopian epidemic dynamics were characterised by an expanding epidemic growth from the beginning of the epidemic until the mid-1990s, followed by a sharp decline in HIV-1 transmissions, which coincided with early behavioural, preventive, and public health awareness campaigns implemented in Ethiopia.
Over the last decades, the rapid expansion of ART has significantly reduced the risk of transmission and improved the survival and quality of life of HIV-infected patients. However, global evidence indicates that the rapid expansion of ART is associated with increase in pretreatment drug resistance (PDR) and acquired drug resistance (ADR), posing threat to both individual outcomes and the prospect of elimination of HIV as a public health threat. Following the increase of PDR to non-nucleoside reverse transcriptase inhibitors (NNRTIs), many countries, including Ethiopia, have switched to the dolutegravir (DTG)-based regimen as first- and second-line therapies. However, differences in naturally occurring polymorphisms (NOPs) have been linked to the development of different mutational pathways, resulting in varying levels of drug resistance against integrase strand transfer inhibitor (INSTIs) among different HIV-1 subtypes. In this PhD thesis work, we assessed the prevalence of PDR in different population groups (young newly HIV-1 infected adults, general population and risk group (Female sex workers, FSWs). Our finding indicated that HIVDR will be an eminent challenge for the HIV epidemic control in Ethiopia.