High Frequency of Non-B Human Immunodeficiency Virus Type 1 (HIV-1) Subtype Specific Mutations at the Protease Gene among Treatment-naive HIV-1 Infected Individuals in Jos, Nigeria

Abstract

Aims: To determine the prevalence of non-B HIV-1 subtype specific mutations in the protease gene among antiretroviral drug-naive individuals in Jos, Nigeria. Study Design: This was a cross-sectional study in which randomly selected blood samples of HIV-1 positive anti-retroviral drug-naïve individuals were used for genotyping assay. Place and Duration of Study: The study was conducted at the adult HIV clinic of the AIDS Prevention Initiative in Nigeria (APIN) programme, Jos University Teaching Hospital (JUTH), Jos, Nigeria between October 2010 and April 2011. Methodology: Of the one hundred and five plasma samples, 100 samples were successfully reverse transcribed and amplified by nested PCR. The amplicons were directly sequenced on an automated ABI genetic analyzer using BigDye Terminator Cycle Sequencing Kit. Subtyping and phylogenetic analyses were performed using the REGA subtyping tool version 2.0 and MEGA 5.0 software. Both the Stanford HIV database algorithm and IAS-USA 2013 drug resistance update were used for interpretation of drug sensitivity. Results: The proportion of the non-B HIV-1 subtypes were as follows: CRF02_AG (48%), G (41%), CRF06_cpx (6%), A (5%). Q58E, a major drug resistance mutation to PI, occurred as a low prevalence mutation in subtype G. The most common mutations observed among the subtypes were I13V, K14R, K20I, M36I, R41K, H69K, V82I and L89M. Conclusion: A non-uniform distribution of non-B HIV-1 subtypes were observed in Jos, Nigeria, with CRF02_AG and G predominating among the antiretroviral drug-naive individuals. Among the different subtypes in circulation, there was a high prevalence of minor mutations and natural polymorphisms associated with the protease gene. Such mutations define the subtype diversity which may impact on virulence and drug ‘responses’, thus further studies are needed to evaluate the clinical implications of these mutations.