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.
