Antiretroviral resistance among HIV-1 patients on first-line therapy attending a comprehensive care clinic in Kenyatta National Hospital, Kenya: a retrospective analysis.

INTRODUCTION: Antiretroviral therapy plays a major role in reducing the impact of Human Immunodeficiency Virus/Acquired Immune Disease Syndrome, especially in resource-limited settings. However, without proper infrastructure, it has resulted in emergence of drug resistance mutations in infected populations. To determine drug resistance mutations among patients attending a comprehensive care facility in Nairobi, 65 blood samples were successfully sequenced. METHODS: Whole blood samples were also tested for CD4+T-cell count and plasma HIV-1 RNA Viral load. Drug-resistance testing targeting the HIV-1 RT gene was determined. Patients were on first line ART that consisted of two NRTIs, and one NNRTI. RESULTS: Females were younger (mean 42) than males (mean 45) and lower median CD4+ counts (139 cells/µl) than males (152 cells/µl). The prevalence of drug resistance mutations (any major mutation) in this population was 23.1% (15/65). Major NRTI mutations were detected in 11 patient samples, which included M184V (n = 6), M41L (n=3), D67N (n=2), K219Q (n=3) and T215F (n=2). Major NNRTI mutations were detected in 14 patient samples. They included K103N (n = 10), G190A (n = 1), Y181C (n = 1) and Y188L (n = 1). CONCLUSION: Presence of major mutations in this study calls for proper laboratory infrastructure to monitor treatment as well as regular appraisals of available regimens.

Predicted HIV-1 coreceptor usage among Kenya patients shows a high tendency for subtype d to be cxcr4 tropic.

BACKGROUND: CCR5 antagonists have clinically been approved for prevention or treatment of HIV/AIDS. Countries in Sub-Saharan Africa with the highest burden of HIV/AIDS are due to adopt these regimens. However, HIV-1 can also use CXCR4 as a co-receptor. There is hence an urgent need to map out cellular tropism of a country's circulating HIV strains to guide the impending use of CCR5 antagonists. OBJECTIVES: To determine HIV-1 coreceptor usage among patients attending a comprehensive care centre in Nairobi, Kenya. METHODS: Blood samples were obtained from HIV infected patients attending the comprehensive care centre, Kenyatta National Hospital in years 2008 and 2009. The samples were separated into plasma and peripheral blood mononuclear cells (PBMCs). Proviral DNA was extracted from PBMCs and Polymerase Chain reaction (PCR) done to amplify the HIV env fragment spanning the C2-V3 region. The resultant fragment was directly sequenced on an automated sequencer (ABI, 3100). Co-receptor prediction of the env sequences was done using Geno2pheno [co-receptor], and phylogenetic relationships determined using CLUSTALW and Neighbor Joining method. RESULTS: A total of 67 samples (46 treatment experienced and 21 treatment naive) were successfully amplified and sequenced. Forty nine (73%) sequences showed a prediction for R5 tropism while 18(27%) were X4 tropic. Phylogenetic analysis showed that 46(69%) were subtype A, 11(16%) subtype C, and 10(15%) subtype D. No statistical significant associations were observed between cell tropism and CD4+ status, patient gender, age, or treatment option. There was a tendency for more X4 tropic strains being in the treatment experienced group than the naive group: Of 46 treatment experiencing participants, 14(30%) harboured X4, compared with 4(19%) of 21 of the treatment-naïve participants, the association is however not statistically significant (p = 0.31). However, a strong association was observed between subtype D and CXCR4 co- receptor usage (p = 0.015) with 6(60%) of the 10 subtype D being X4 tropic and 4(40%) R5 tropic. CONCLUSION: HIV-1 R5 tropic strains were the most prevalent in the study population and HIV infected patients in Kenya may benefit from CCR5 antagonists. However, there is need for caution where subtype D infection is suspected or where antiretroviral salvage therapy is indicated.