DETERMINATION OF ANTIRETROVIRAL DRUG RESISTANCE MUTATIONS AMONG HIV- 1 INFECTED PARTICIPANTS FROM SELECTED CARE CENTRES IN KENYA

Abstract

Majority of people infected with HIV-1 in the developing countries continue to benefit from scaled-up access to antiretroviral medications. But the frequent appearance of drug resistance mutations poses significant threats to success of treatment. This study aimed to determine HIV drug resistance-associated mutations (DRAMs) among HIV-1 infected patients on treatment in Kenya. A total of 83 patients on highly active antiretroviral therapy (HAART) meeting the inclusion criteria were enrolled from care and treatment centres in Kiambu, Kilifi, Kajiado, Nakuru, Kisumu and Homabay counties. Viral RNA and DNA were amplified from plasma and peripheral blood mononuclear cells (PBMCs) respectively, and the pol-RT region of HIV-1 sequenced in 54 patients. Sequences were analyzed for DRAMS and interpreted using the Stanford HIV Drug Resistance Interpretation algorithm. Viral loads and CD4 counts were also determined using m2000 Abbot real-time assay and FACs respectively. The median participant age and duration of HAART were 34 years and 33 months respectively. The median CD4 T cell counts and viral load were 399 (range, 12-1954) cells/mm3 and 3.51 (range, 1.59-5.96) log10 HIV-1 RNA copies respectively. In total, 27.8% of the patients harboured reverse transcriptase inhibitor DRAMS, with 73.3% of the mutations conferring resistance to both nucleoside RTIs (NRTIs) and non-nucleoside RTIs (NNRTIs). Mutation frequency of all DRAMS was 25 (47.2%) and 52.8% for NRTI and NNRTI types respectively. The most common of NRTI and NNRTI mutations were M184V/I and K103N occurring respectively in 73.3% and 60% of the patients with DRAMs, appearing at a mutation frequency of 44% and 32.1% respectively. Most of the subjects were infected by viruses of subtypes A (57.4%), with the rest being recombinant (22.2%), D (14.8%) and C (5.6%) strains. Recombinant viruses had the highest ratio of average DRAMs per subtype at 4.5, followed by subtypes A (3.6), C (3) and D (2.3). No residual DRAMs were observed in patients with viral load less than 1,000 RNA copies/ml. A significant proportion of patients receiving anti-HIV treatment in Kenya have developed multiple drug resistance. Viral load and Drug-resistance testing should therefore be integrated to monitoring programs to improve treatment efficacy.