Rifampicin + Dolutegravir

Rifampicin + dolutegravir is a drug combination used in the treatment of patients with HIV-1 infection who also have tuberculosis (TB). This combination requires special dosing considerations due to a significant drug-drug interaction. ## Pharmacokinetic Interaction Rifampicin is a potent enzyme inducer that significantly affects dolutegravir's metabolism. When co-administered, rifampicin decreases dolutegravir concentrations by inducing UGT1A1 and CYP3A4 enzymes, which are responsible for dolutegravir metabolism[1][4]. This interaction results in: - 43% decrease in dolutegravir Cmax - 54% decrease in dolutegravir AUC - 72% decrease in dolutegravir Ctrough[4] ## Dosing Recommendations Due to this interaction, current guidelines recommend: - Doubling the dose of dolutegravir to 50mg twice daily when co-administered with rifampicin[1][4] - Maintaining this increased dosing for approximately 2 weeks after stopping rifampicin, as the inducing effect may persist[4] - In the presence of integrase class resistance, this combination should be avoided[4] ## Clinical Evidence The INSPIRING study provided clinical evidence supporting this dosing approach: - Phase 3a randomized, open-label study with 113 participants - All participants had been taking rifampicin-based TB therapy for at least 8 weeks - Participants received either dolutegravir (50mg twice daily) or efavirenz (600mg once daily) - At 24 weeks, 81% of participants achieved viral suppression[5] More recent evidence from a phase 2b non-comparative placebo-controlled randomized trial by Griesel and colleagues suggests that dolutegravir 50mg once daily in a fixed-dose combination with tenofovir and lamivudine (TLD) may be adequate without an additional evening dose[1]. This study showed: - Similar safety profiles between once-daily and twice-daily dosing - Equivalent viral suppression rates at week 24 (83% in both arms) - No emergent integrase strand transfer inhibitor resistance mutations in patients with virological failure[1] ## Alternative Approaches For patients who cannot tolerate rifampicin or where drug interactions are problematic, rifabutin may offer an alternative: - Rifabutin is a less potent enzyme inducer than rifampicin - When co-administered with dolutegravir 50mg once daily, no dose adjustment is needed - Rifabutin decreases dolutegravir's volume of distribution by 33.1% but does not affect the area under the concentration-time curve[3] ## Clinical Implications The requirement for twice-daily dosing of dolutegravir with rifampicin creates challenges in high-burden settings: - Adherence issues with twice-daily dosing - Drug stock-out concerns - Increased pill burden for patients already managing multiple medications for HIV and TB[1] The potential for once-daily dosing, if confirmed in larger studies, could significantly simplify treatment for HIV/TB co-infected individuals.

Other names

dolutegravir + rifampicin