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ABCB1 Polymorphism in HIV-Infected Individuals Taking Antiretroviral Drugs
HariOm Singh1, Dharmesh Samani1, Supriya D Mahajan2
1Department of Molecular Biology, ICMR-National AIDS Research Institute, Pune, 411026, India.
AIDS Research and Treatment
|October 27, 2025
Summary
Genetic variants in the ABCB1 gene may influence antiretroviral (ARV)-associated hepatotoxicity in HIV patients. Certain ABCB1 haplotypes, like TC, were linked to increased risk, while CC and TT haplotypes showed protective effects against liver damage.
Area of Science:
- Pharmacogenomics
- Hepatology
- Infectious Diseases
Background:
- P-glycoprotein (P-gp), an ABC transporter, affects drug elimination and exposure.
- The ABCB1 gene is implicated in the elimination of non-nucleoside reverse-transcriptase inhibitors (NNRTIs).
- Genetic variations in ABCB1 can impact drug exposure and toxicity.
Purpose of the Study:
- To investigate the association between ABCB1 gene polymorphisms (1236C/T and 3435C/T) and antiretroviral (ARV)-associated hepatotoxicity.
- To explore the influence of ABCB1 variants on the severity of liver injury in HIV-infected individuals.
Main Methods:
- A cross-sectional study involving 165 HIV-infected individuals and 155 healthy controls.
- Genotyping of ABCB1 1236C/T and 3435C/T polymorphisms using the PCR-RFLP method.
- Analysis of genotype and haplotype associations with hepatotoxicity, considering factors like alcohol use and specific ARV regimens (e.g., nevirapine).
Main Results:
- The TC haplotype showed a trend towards increased risk of severe hepatotoxicity (OR=1.96, p=0.06).
- CC and TT haplotypes were associated with a reduced risk of severe hepatotoxicity (ORs ranging from 0.09 to 0.34, p<0.05).
- The 1236TT genotype combined with nevirapine use suggested a potential risk for hepatotoxicity severity (OR=2.11, p=0.55).
Conclusions:
- ABCB1 haplotypes may play a role in modulating the severity of ARV-induced hepatotoxicity.
- While individual polymorphisms showed no significant association, the TC haplotype and 1236TT genotype with nevirapine use indicated potential risks.
- CC and TT haplotypes demonstrated protective effects, warranting further investigation in larger cohorts.
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