Effect of Abcb1 C3435t Polymorphism on Clinical Outcomes in Hiv Patients on Lopinavir-based Antiretroviral Therapy at Kenyatta National Hospital

Abstract

Background Genetic variation is important consideration in drug disposition and overall clinical response in patients on antiretroviral therapy. ABCB1 affects disposition of many drugs and thus affects the pharmacokinetics of drugs and ultimately treatment response. Polymorphisms of ABCB1 especially ABCB1 C3435T polymorphism may affect pharmacokinetics of lopinavir by interfering with efflux of lopinavir from sanctuary sites and thus affect CD4 treatment response and other clinical outcomes of patients infected by human immunodeficiency virus (HIV). Objectives The main objective was investigating effects of ABCB1 C3435T polymorphisms on clinical outcomes in HIV patients on lopinavir-based antiretroviral therapy (ART) regimens at the Comprehensive Care Centre (CCC) of Kenyatta National Hospital (KNH). Method The study design was a historical cohort carried out among Kenyan HIV patients on lopinavir-based regimens attending KNH CCC clinic and entailed collection of patient data. Patient clinical and demographic information were abstracted from the medical records using a data abstraction form. Blood samples were drawn from the participants. PureLink® genomic DNA extraction mini kit was used for the extraction and purification of genomic DNA. TaqMan® drug genotyping assay and protocol was used in the DNA amplification and genotyping by use of real time polymerase chain reaction. Data analysis was conducted by use of STATA software version 10. Results There were 84 study participants comprising 59.5% female and 40.5% male. All were on a lopinavir-based regimen. Prevalence of the ABCB1 3435CC wild-type genotype was 64 (76.2%) while that of the heterozygous CT genotype was 19 (22.6%), and the TT variant genotype was 1 (1.2%). ABCB1 C3435T polymorphism was significantly associated with creatinine levels (p=0.001) 6 months after therapy on lopinavir-based regimens. Study participants with the CT genotype had lower creatinine levels after 6 months on lopinavir-based regimens than those with the CC genotype. In addition, study participants with the CT genotype had mean change of CD4 count of 71 after six months on lopinavir-based regimens compared to those with the CC genotype who had a mean change of CD4 count of 28. ABCB1 C3435T genotypes had no significant association with haemoglobin levels, ALT levels and body mass index.

Conclusion This study reveals that the patients with heterozygous ABCB1 3435 CT genotype exhibit better immunological profile and better renal function. Therefore, genotyping for ABCB1 C3435T polymorphism would help predict patients who would respond effectively to lopinavir-based regimens. However, more genotypic studies on other ABCB1 polymorphisms need to be done.