The effects of CYP2B6 Polymorphisms on CD4 cell count in HIV Patients on Nevirapine Based Regimens at Kenyatta National Hospital
Angima, James A.
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Background: The CD4 cell count has become a valuable indicator of immunological function in the management of HIV infection. Regular measurements of CD4 levels have been utilized to assess immunological response to antiretroviral drugs in HIV/AIDS patients. Fluctuations in CD4 cell counts can be influenced by genetic characteristics of HIV/AIDS patients. CYP2B6 gene is a drug metabolizing enzyme that may influence CD4 cell counts due to its effect on the disposition of antiretroviral drugs. Objectives: The main objective of this study was to determine the prevalence of polymorphisms of CYP2B6 516G>T and CYP2B6 983T>C and the influence of these polymorphisms on the CD4 cell levels on patients on nevirapine based regimens at Kenyatta National Hospital. Methodology: DNA extraction and genotyping were performed on 204 archived blood samples of HIV positive patients who had been on nevirapine based antiretroviral regimens. The DNA extraction was performed using PureLink® Genomic DNA extraction protocol (Life Technologies, Carlsbad, CA). Genotyping was performed using TaqMan® Drug Metabolism genotyping assay protocol (Life Technologies, Carlsbad, CA). Multi-linear regression was performed using STATA version 11 to establish association between CYP2B6 516G>T and 983T>C single nucleotide polymorphisms and CD4 cell counts using patient social-demographic data adapted from a study conducted by Makori et al 2014. Results: One hundred and ninety four (194) blood samples were genotyped for the expression of CYP2B6 516G>T SNP. The number of samples that expressed CYP2B6 516GG wild-type genotype was 89 (45.9%). Seventy three (37.6%) samples expressed the heterozygous GT genotype while 32 (16.5%) expressed the homozygous TT genotype. The allele frequencies for CYP2B6 516G>T SNP in the study population were; 64.7% for G and 35.3% for the T allele (χ2= 6.04; P<0.014). Two hundred and four (204) blood samples were genotyped for the expression of CYP2B6 983T>C SNP. One hundred and eighty three (89.7%) samples expressed CYP2B6 983TT genotype, while 19 (9.3%) and 2 (1%) expressed the heterozygous TC and homozygous CC genotypes respectively. Allele frequencies for the CYP2B6 983T>C SNP were 94.4% for T allele and 5.6% for C allele (χ2= 3.165; P<0.075). On bivariable analysis, there was no association between CYP2B6 516G>T and 983T>C genotypes and baseline, current and the rate of change of CD4 cell counts. Discussion This study has shown that the prevalence of CYP2B6 516G>T and 983T>C genotypes in the study population was similar to those reported in other African populations. There was no association between CYP2B6 516G>T and 983T>C genotypes and CD4 cell counts which was at variance with previous studies. Conclusion: This study found no association between the expression of CYP2B6 516G>T and 983T>C genotypes and CD4 cell counts. Nevirapine plasma concentrations need to be determined to infer any association between these genotypes and CD4 cell counts.
University of Nairobi
A thesis submitted in partial fulfillment of the requirements for the award of the degree of Master of Science in molecular pharmacology of the University of Nairobi
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