Title : Clinical relevance of the 516 G>T polymorphism in CYP2B6 and its effects on efavirenz concentrations in patients with HIV and tuberculosis: A meta-analysis
Abstract:
Introduction
Efavirenz is a long-acting antiretroviral drug that has been available for several decades. Despite being an older medication, it remains widely used in certain regions due to its low susceptibility to resistance. However, its use is associated with frequent adverse effects, mainly due to toxicity, particularly when coadministered with rifampicin in patients with HIV-TB coinfection. The most common adverse effects include hepatotoxicity and central nervous system (CNS) disturbances. The enzyme CYP2B6 plays a crucial role in the metabolism of efavirenz and has been directly linked to these adverse effects.
Objective
This study aims to analyze the impact of polymorphisms in the CYP2B6 gene, specifically the 516 G>T variant, on efavirenz metabolism. We intent to evaluate differences in plasma efavirenz concentrations among the GG, GT, and TT genotypes.
Methods
A systematic review was conducted using PubMed, Embase, and Cochrane databases to identify studies published up to March 2025 that examined the effects of the CYP2B6 516 G>T polymorphism on efavirenz treatment. The primary outcome of interest was plasma efavirenz concentration. Data were analyzed using pooled relative risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI), applying random-effects models.
Results
Five studies including a total of 373 patients met the inclusion criteria. Compared with the GG and GT genotypes, individuals with the TT genotype exhibited significantly higher plasma efavirenz concentrations. The mean differences in plasma concentration between the GT-TT and GG-TT subgroups were 5.65 µg/mL (95% CI: 2.90–8.40) and 6.41 µg/mL (95% CI: 3.52–9.30), respectively, both statistically significant (p < 0.05). No significant difference was observed between the GG and GT subgroups.
Conclusion
These findings suggest that individuals with the TT genotype of the CYP2B6 516 G>T polymorphism are at a higher risk of experiencing toxic effects due to elevated plasma efavirenz concentrations. This underscores the importance of pharmacogenetic testing to optimize efavirenz dosing and minimize toxicity, particularly in patients carrying the TT genotype. The observed heterogeneity among studies may be attributed to ethnic variability and differences in sample sizes.
