Is there a need to increase the dose of efavirenz during concomitant rifampicin-based antituberculosis therapy in sub-Saharan Africa? The HIV-TB pharmagene study

Aims: The current HIV treatment guidelines are inconsistent about the need for weight-based efavirenz dose adjustment during rifampicin containing antituberculosis (anti-TB) cotreatment. We investigated effect of rifampicin-based anti-TB cotreatment on plasma efavirenz exposure and treatment outcome, considering effect of CYP2B6 genotype and bodyweight. Patients & methods: HIV-only (arm 1, n = 285) or TB–HIV (arm 2, n = 208) coinfected patients were enrolled and received efavirenz-based ART alone or with rifampicin-based anti-TB therapy, respectively. Plasma efavirenz concentrations at 4th and 16th weeks, viral load and CD4 cell count at 24th and 48th weeks were determined. Results: The mean plasma efavirenz concentration at weeks 4 (p = 0.03) and 16 (p = 0.08) was inconsistently higher in arm 2 than arm 1, mainly in CYP2B6*6 carriers. Effect of bodyweight on efavirenz pharmacokinetics was significant only in arm 1, but not in arm 2. Proportion of patients with nondetectable viral load (≤50 copies/ml) at ...