HAART Regimens Compatible with Rifampin
For patients requiring rifampin therapy, the recommended HAART regimens are: dolutegravir 50 mg twice daily (not once daily) plus tenofovir/emtricitabine or lamivudine, OR efavirenz 600 mg daily plus two NRTIs. 1
Primary Recommended Regimens
Dolutegravir-Based Therapy
- Dolutegravir must be dosed at 50 mg twice daily (not the standard once-daily dose) when co-administered with rifampin for active tuberculosis treatment 1
- Combine with tenofovir alafenamide (TAF) or tenofovir disoproxil fumarate (TDF) plus emtricitabine (FTC) or lamivudine (3TC) as the NRTI backbone 1
- This dose adjustment is necessary because rifampin significantly reduces dolutegravir concentrations through CYP3A4 induction 1
Efavirenz-Based Therapy
- Efavirenz 600 mg once daily can be used without dose adjustment when combined with rifampin 1
- Pair with two NRTIs (tenofovir plus emtricitabine or lamivudine) 1
- Despite rifampin's enzyme-inducing effects, standard efavirenz dosing maintains adequate drug levels 2
Important Caveat About Tenofovir Alafenamide
- TAF has a pharmacokinetic interaction with rifampin that reduces TAF levels, though clinical data are limited 1
- If using TAF with rifampin, close monitoring of HIV RNA levels is essential 1
- TDF may be the safer tenofovir option when rifampin is required 1
Alternative Option (Third-Line)
Ritonavir-Boosted Protease Inhibitor Regimens
- Should only be used if dolutegravir and efavirenz are not options 1
- Requires substituting rifabutin 150 mg daily for rifampin (not using rifampin itself) 1
- Combine boosted PI with tenofovir/emtricitabine or lamivudine 1
- This is explicitly a last-resort option due to complexity of drug-drug interactions 1
Regimens That Are Contraindicated with Rifampin
The following HAART regimens cannot be used with rifampin due to severe drug-drug interactions: 1
- Bictegravir/TAF/FTC - inadequate data and significant interactions 1
- Dolutegravir/lamivudine (2-drug regimen) - not recommended with rifampin 1
- Darunavir boosted with ritonavir or cobicistat - contraindicated 1
- Doravirine - contraindicated 1
- Elvitegravir/cobicistat combinations - contraindicated 1
- Long-acting cabotegravir plus rilpivirine - contraindicated 1
- Rilpivirine-containing regimens - contraindicated 1
- Etravirine - contraindicated 1
Critical Timing Considerations
- Rifampin's enzyme induction reaches maximum effect within 1 week of starting therapy 3
- Induction effects persist for approximately 2 weeks after rifampin discontinuation 3, 4
- When stopping rifampin, antiretroviral drug levels will increase as induction wears off, requiring vigilance for toxicity 4
- When starting rifampin in a patient already on HAART, immediate regimen adjustment is necessary to prevent subtherapeutic antiretroviral levels 4
Special Situations
Tuberculosis Preventive Therapy
- For 3HP regimen (weekly rifapentine plus isoniazid for 12 weeks): dolutegravir 50 mg once daily is adequate 1
- For 1HP regimen (daily rifapentine plus isoniazid for 1 month): dolutegravir 50 mg twice daily is required 1
Active Opportunistic Infections
- The 2-drug dolutegravir/lamivudine regimen should not be initiated in patients with active opportunistic infections, even without rifampin 1
- Standard 3-drug regimens are preferred when treating active tuberculosis 1
Common Pitfalls to Avoid
- Never use standard once-daily dolutegravir dosing with rifampin - this will result in subtherapeutic levels and treatment failure 1
- Do not assume all integrase inhibitors behave similarly - bictegravir cannot be used with rifampin while dolutegravir (at increased dose) can 1
- Rifabutin is not interchangeable with rifampin for first-line tuberculosis treatment - rifabutin is only used when protease inhibitors are absolutely necessary 1
- Monitor for overlapping toxicities - both tuberculosis drugs and antiretrovirals can cause hepatotoxicity, requiring close monitoring 5