Genotyping Of Human Immunodeficiency Virus Type-1 In Relation To Antiretroviral Drug Resistance In Western Province, Kenya

ABSTRACT Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS) is the main pandemic in the world today. Sub-Saharan Africa bears the brunt of the catastrophe. Although it harbours less than 10% of the world‟s population, it comprises 60% of all people living with HIV/AIDS globally. Kenya has a National adult HIV/AIDS prevalence of 7.4%. In recent times, expansion of access to antiretroviral therapy in resource-limited settings has gained prominence. However, it is estimated that in Africa, only one million people out of the over four million are receiving ART. Highly active antiretroviral therapy has markedly improved the prognosis of HIV-infected patients by controlling HIV replication. However, it has been observed that HAART fails to control HIV replication in an increasing number of patients as a result of a complex array of causes. One of these is the emergence of drug resistance leading to antiretroviral therapy failure. More seriously, HIV drug resistance can be transmitted and lead to treatment failure. The main objective of this study was to determine the circulating HIV-1 subtypes in Western Kenya, and the prevalence of mutations in the protease gene that confer antiretroviral resistance in the various subtypes. A total of 75 patients were sampled randomly from a cohort of 1000 clients receiving ARVs in Busia District Hospital. A single blood draw (5ml) was collected, packaged and shipped to KEMRI HIV laboratories in Nairobi for genotyping and analysis of drug associated mutations. Polymerase chain reaction, sequencing and phylogenetic analysis of HIV-1 partial protease showed that majority of strains were of subtype A1 (39/75) followed by D (21/75), C (5/75) and G (5/75) with possible recombinants of AC (1/75) and AD (1/75). Other prevalent subtypes included, A2 (2/75) and B (1/75). The generated sequences were further analysed using the sequence analysis Stanford HIV drug resistance database for drug-associated resistance mutations. Resistance associated mutations were detected in 12 (16.0%) isolates as follows: Subtypes A1 (n=10), subtype G (n=1) and subtype C (n=1). The analysis further indicated that major protease mutations such as D30N, V32I, M46I, and I47L were circulating in this region among patients unexposed to this class of ARVs. This is contrary to the earlier observations in which these mutations have been documented mainly in patients on protease-based regimens, an aspect attributed to transmitted-resistance mutations. A total of 4 subtypes A1 isolates were found to posses V32L and T74S mutations that result to reduced susceptibility to Nelfinavir. One subtype C isolate had D30N, G48R and G73S mutations, which are known to cause high-level resistance to Nelfinavir. Other minor protease mutations such as M36I and K20I were also detected. Such mutations are common to some patients not previously exposed to ARVs, especially in non-B subtypes. There is need for regular surveillance of drug resistance and monitoring of mutations conferring resistance to ARVs in both treated and untreated patient population in order to achieve successful treatment outcomes.