HIV-1 Genetic Diversity and Pre-treatment Drug Resistance Mutations Among Recently Diagnosed HIV-1 Infected Antiretroviral-Naive individuals in Addis Ababa, Ethiopia
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Date
2019-11
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Addis Ababa University
Abstract
Background: Africa is a region hardest hit by the Human Immunodeficiency Virus (HIV) among other continents on the globe with the highest rise of the infection in the eastern and southern parts. Besides, the development of Pretreatment drug resistance (PDR) is becoming an obstacle to the success of antiretroviral therapy (ART). Despite ART scale-up, there is only limited information with regard to HIV-1 PDR in Ethiopia. Moreover, with increasing movement of people, HIV-1 variants other than the predominant subtype C may be introduced and intermixed from the neighboring countries. Therefore, this study was aimed to assess HIV-1 Genetic Diversity and Pre-treatment Drug Resistance Mutations among recently diagnosed HIV-1 Infected Antiretroviral-Naive individuals in Addis Ababa, Ethiopia.
Method: Institutional based cross-sectional study was conducted from June 2018 up to December 2018 in Addis Ababa, Ethiopia. Plasma samples (n=72) from ART-naive study participants were collected for sequencing of partial HIV-1 pol region covering the complete protease (PR) and partial reverse transcriptase (RT) regions (nucleotides 2253 to 3539 of reference strain HXB2) using in-house assay. Both Stanford University HIV drug resistance
database (Stanford HIVdb) and the International Antiviral Society-USA (IAS-USA) 2019 mutation list Algorithms were used to assess the presence of PDR mutations.
Result: From 72 eligible plasma samples, 75% (54/72) of them were successfully amplified. Out of this, 51/54 (94.4%) were successfully sequenced and analyzed. According to the Stanford HIVdb and IAS-USA mutation list, 9.8% (5/51) of analyzed samples had at least one PDR Mutation. PDR mutations to Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTIs) was the most frequently detected mutation (7.8% and 9.8%, according to Stanford HIVdb and IAS-USA Algorithm respectively) followed by Nucleoside Reverse Transcriptase Inhibitors (NRTIs) (1/51, 2% by both Algorithms) and Protease Inhibitors (PIs) (1/51, 2%, According to the Stanford HIVdb only). One individual had PDR mutations that confer resistance to NNRTIand NRTI simultaneously. In addition, a high rate of polymorphism was observed both in the PR and RT regions. With regard to HIV-1 genetic diversity, phylogenetic analysis showed that all 51/51 (100%) of the study participants were infected with subtype C virus.
Conclusion and Recommendations: This study presents additional evidence for increased level of PDR and persistence HIV-1C clade homogeneity after 15 years of the rollout of ART and 3 decades of HIV-1C circulation in Ethiopia, respectively. Therefore, routine genotypic drug resistance testing is warranted for successful ART programs and the overall prevention of HIV transmission in the country to support the global efforts in achieving the third 90 of the UN target.
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Keywords
HIV, Genetic diversity, HIV drug resistance, HIV Subtype