High Prevalence of Antiretroviral Resistance in Treated Ugandans Infected with Non-subtype B Human Immunodeficiency Virus Type 1

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Abstract
This study examined the emergence and prevalence of drug-resistant mutations in reverse transcriptase and protease coding regions in human immunodeficiency virus type 1 (HIV-1)-infected Ugandans treated with antiretroviral drugs (ARV). Genotypic resistance testing was performed on 50 and 16 participants who were enrolled in a cross-sectional and longitudinal observational cohort, respectively. The majority of the 113 HIV-1 PR-RT sequences were classified as subtypes A and D. Drug resistance mutations were prevalent in 52% of ARV-experienced individuals, and 17 of 27 ARV-resistant isolates had three mutations or more in reverse transcriptase. Resistance mutations in protease were less prevalent but only 17 of the 50 patients were receiving a protease inhibitor upon sample collection. Mutations conferring drug resistance were also selected in 3 of 16 participants in the longitudinal cohort, i.e., less than 8 months after the initiation of ARV treatment. Rapid emergence of ARV resistance was associated with poor adherence to treatment regimens, which was related to treatment costs. ARV resistance did, however, appear at a slightly higher prevalence in HIV-1 subtype D (21 of 33) than subtype A (7 of 25) infected individuals. Overall, this observational study suggests that ARV-resistant HIV-1 isolates are emerging rapidly in ARV-treated individual in Uganda and possibly other developing countries.

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