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.

BACKGROUND AND

OBJECTIVE

Efavirenz is associated with frequent adverse effects, mainly hepatotoxicity and central nervous system disturbances. The cytochrome P450 enzyme CYP2B6 plays a key role in efavirenz metabolism and is strongly linked to these toxicities. This study aimed to evaluate the effect of the CYP2B6 c.516 G>T polymorphism on efavirenz plasma concentrations by comparing individuals with GG, GT, and TT genotypes.

METHODS

A systematic review of four databases was conducted to identify studies published up to March 2025 evaluating the association between the CYP2B6 c.516 G>T polymorphism and efavirenz plasma concentrations. Pooled mean differences with 95% confidence intervals were calculated using random-effects models.

RESULTS

Five studies, including 373 patients, met the inclusion criteria. Individuals with the TT genotype showed significantly higher plasma efavirenz concentrations compared with GG and GT carriers. The mean differences in plasma concentration between the GT-TT and GG-TT subgroups were 5.65 µg/mL and 6.41 µg/mL, respectively, both statistically significant (p < 0.05). No significant difference was observed between the GG and GT genotypes.

CONCLUSION

This meta-analysis confirms that the CYP2B6 c.516 TT genotype is significantly associated with elevated plasma efavirenz concentration in patients with HIV and tuberculosis. While higher concentrations may increase toxicity risk, this was not directly evaluated in the current pooled analysis. These findings support the potential utility of pharmacogenetic testing to optimize efavirenz dosing and minimize the risk of adverse effects, particularly in carriers of the TT genotype. The observed heterogeneity among studies may be attributed to ethnic variability and differences in sample sizes.