Title : Effect of ABCB1, ABCC4, and GSTP1 gene polymorphisms on the response and toxicities of antiretroviral therapy in Bangladeshi AIDS patients
Abstract:
Background: Antiretroviral therapy was reported to show varying degree of responses and toxicities. The inter-individual variation of the therapy outcomes is due to different factors including biological factors. Genetic factors are one of the leading causes of this variation. Therefore, it is warranted to investigate the influence of genetic factors that leads to variation of the therapy outcomes.
Objective: Our objectives were to evaluate the role of genetic polymorphisms in ABCB1, ABCC4 and GSTP1 on the drug response and toxicities of antiretroviral therapy in AIDS patients and to identify molecular (genetic) marker for selecting better treatment regimen and reducing toxicities
Methodology: A total 414 AIDS patients were recruited from Infectious Diseases hospital (IDH: 208) &(BSMMU: 206) of Bangladesh receiving Lamivudine-300 mg+ Tenofovir-300mg + Efavirenz-400mg (for 6 months). PCR-RFLP had been applied to determine the genetic polymorphisms. Viral load and regimen change and drug induced toxicities have been evaluated from recorded hospital data of the patients as well as it was matched with the data obtained from interview of the patients with the help of structured questionnaire.
Result: ABCB1 gene was associated with the high viral load such as for CT (p= 0.0095, OR=0.49), TT (p= 0. 0.0068, OR=0.40), and for CT+TT (p= 0.0018, OR=0.45) as well as regimen change (drug resistance) like for CT (p= 0.0091, OR=0.50), TT (p= 0. 0.0017, OR=0.36), and for CT+TT (p= 0.0009, OR=0.45). On the other hand, GSTP1 gene was linked with drug induced toxicities like drug allergy (hypersensitivity) such as for AG (p= 0.048, OR=1.99), GG (p= 0.04, OR= 2.39), and for AG+GG (p= 0.016, OR=2.2), nausea and vomiting: for GG (p= 0.017, OR= 2.96), and for AG+GG (p= 0.025, OR=1.9), hyperacidity: for GG (p= 0.023, OR= 2.96), and for AG+GG (p= 0.026, OR=2.16) , diarrhea: GG (p= 0.031, OR= 2.98), and for AG+GG (p= 0.03, OR=2.22) and insomnia: for AG+GG (p= 0.039, OR=2.1). No other significant association was observed for ABCB1, ABCC4 and GSTP1.
Conclusion: ABCB1 gene was associated with viral load and drug resistance. On the other hand, GSTP1 gene was related with drug induced toxicity in AIDS patients.
