Rifampicin and Atazanavir Co-Administration
Direct Answer
Rifampicin is absolutely contraindicated with atazanavir (with or without ritonavir boosting) and must never be co-administered. 1
FDA Contraindication
The FDA drug label explicitly states that rifampicin is contraindicated in patients receiving atazanavir due to rifampicin's ability to substantially decrease plasma concentrations of atazanavir, resulting in loss of antiviral efficacy and development of viral resistance. 1
Clinical Evidence Supporting the Contraindication
Pharmacokinetic Failure with Ritonavir-Boosted Atazanavir
Even with ritonavir boosting (atazanavir 300 mg + ritonavir 100 mg daily), rifampicin co-administration results in subtherapeutic atazanavir levels in over 50% of measurements, falling below the minimum recommended trough of 150 ng/mL needed to suppress wild-type HIV replication. 2
Studies attempting higher doses of atazanavir (300-400 mg every 12 hours) with rifampicin demonstrated mean trough concentrations of only 44-113 ng/mL—well below therapeutic targets—making this combination clinically futile. 3
Severe Hepatotoxicity Risk
When rifampicin is initiated first and atazanavir/ritonavir is subsequently added, severe hepatotoxicity and gastrointestinal toxicity occur rapidly, forcing drug discontinuation within days. 4
The sequence of drug initiation matters critically: adding protease inhibitors to existing rifampicin therapy creates particularly dangerous hepatotoxic interactions. 4
Recommended Alternative Regimens
First-Line Alternative: Rifabutin Substitution
For HIV-infected patients requiring TB treatment while on atazanavir/ritonavir, substitute rifabutin for rifampicin with appropriate dose reduction. 5
Rifabutin dose: 150 mg daily (not 300 mg) when combined with ritonavir-boosted protease inhibitors. 5
Rifabutin is a less potent CYP3A4 inducer than rifampicin, making it compatible with protease inhibitor-based regimens when dose-adjusted. 6
The TB regimen becomes: rifabutin 150 mg daily + pyrazinamide + ethambutol for 6 months (2-month intensive phase with all three drugs, followed by 4-month continuation phase). 5, 6
Alternative Antiretroviral Strategy: Switch to Efavirenz
If rifampicin-based TB therapy is mandatory (e.g., rifabutin unavailable), switch the antiretroviral regimen from atazanavir to efavirenz 600 mg daily plus two NRTIs. 5, 6
Efavirenz at standard 600 mg daily dosing is recommended by most experts when co-administered with rifampicin, though FDA labeling suggests 800 mg daily for patients >60 kg. 5
This allows use of the superior rifampicin-based TB regimen (rifampicin + isoniazid + pyrazinamide + ethambutol for 2 months, then rifampicin + isoniazid for 4 months). 5
Last Resort: Non-Rifamycin TB Regimen
If neither rifabutin substitution nor antiretroviral switching is feasible, a non-rifamycin TB regimen may be used, though this is suboptimal. 5
- Such regimens require 9-12 months of treatment, have lower cure rates, and are generally not recommended for active TB. 5, 7
Critical Timing Considerations
Washout Period After Rifampicin Discontinuation
Wait at least 2 weeks after the last rifampicin dose before starting atazanavir or other protease inhibitors, as rifampicin's CYP3A4 induction persists for this duration. 6
This washout period allows hepatic enzyme activity to normalize and prevents subtherapeutic antiretroviral concentrations. 6
Monitoring Requirements
Management of HIV/TB co-infection with complex drug interactions should be directed by or conducted in consultation with physicians experienced in treating both diseases. 5, 6
Monitor for TB treatment failure, antiretroviral treatment failure, paradoxical TB reactions, synergistic drug toxicities, and rifamycin-related adverse effects. 5
Daily therapy during the TB intensive phase is strongly preferred; intermittent dosing (twice or thrice weekly) in HIV-infected patients has been associated with high relapse rates and emergence of rifamycin resistance, particularly in patients with CD4 counts <100 cells/μL. 5