What is the best recommendation for a patient with active tuberculosis (TB) being treated with rifampin (RIF), isoniazid (INH), pyrazinamide (PZA), and ethambutol (EMB) who wants to start pre-exposure prophylaxis (PrEP) for HIV prevention?

Defer PrEP Until Completion of Tuberculosis Therapy

The best recommendation is to defer starting pre-exposure prophylaxis until the patient completes RIPE tuberculosis therapy (Option A). This approach avoids significant drug-drug interactions between rifampin and PrEP medications while ensuring optimal treatment of active TB, which takes priority for both individual and public health outcomes.

Critical Drug Interaction Concerns

Rifampin's Effect on PrEP Medications

• Rifampin is a potent CYP450 inducer that significantly lowers serum concentrations of many antiretroviral medications, including those used for PrEP 1
• The inducing effect of rifampin on drug metabolism continues for at least 2 weeks after discontinuation, meaning drug interactions persist even after stopping rifampin 1
• This interaction would substantially reduce the efficacy of oral PrEP formulations (both TDF/FTC and TAF/FTC), potentially leaving the patient inadequately protected against HIV acquisition

Why Each PrEP Option Is Problematic During TB Treatment

Option B (TDF/FTC) and Option D (TAF/FTC):

• While tenofovir and emtricitabine have relatively few drug-drug interactions in general 2, the specific interaction with rifampin during active TB treatment has not been adequately studied for PrEP dosing
• The available pharmacokinetic data 3 examined these drugs in HIV-infected patients already on treatment (not PrEP), where the clinical context and drug exposure requirements differ
• Suboptimal PrEP drug levels due to rifampin induction could result in HIV acquisition during a critical period when the patient is immunologically stressed from active TB

Option C (Injectable Cabotegravir):

• Cabotegravir is metabolized by UGT1A1 and UGT1A9 enzymes, which are also induced by rifampin
• Rifampin significantly reduces cabotegravir exposure, compromising PrEP efficacy
• This option is contraindicated during rifampin-containing regimens

Prioritizing Active TB Treatment

TB Treatment Takes Precedence

• Active tuberculosis requires immediate, uncompromised treatment with a rifampin-containing regimen for optimal outcomes [1, 4
• The standard 6-month RIPE regimen is highly effective and should not be altered to accommodate PrEP initiation 4
• Switching from rifampin to rifabutin solely to accommodate PrEP would compromise TB treatment efficacy, as rifabutin is typically reserved for situations where patients are already on antiretroviral therapy 1

Public Health Considerations

• Treating active TB effectively prevents transmission to others and is a public health priority
• The patient is HIV-negative, meaning there is no urgent need to start antiretroviral medications immediately (unlike HIV-positive patients where treatment timing is critical)
• PrEP can be safely deferred for 6 months without compromising the patient's long-term HIV prevention strategy

Recommended Clinical Approach

During TB Treatment (Months 0-6)

• Complete the full 6-month RIPE regimen without modification 1, 4
• Counsel the patient on HIV risk reduction strategies during this period (condom use, partner testing, avoiding high-risk exposures)
• Monitor TB treatment response with sputum cultures at 2 months 1
• Ensure directly observed therapy (DOT) for optimal TB treatment adherence 1

After TB Treatment Completion

• Wait at least 2 weeks after the last dose of rifampin before initiating any PrEP regimen 1
• This waiting period allows rifampin's enzyme-inducing effects to dissipate
• At that point, any standard PrEP regimen (oral TDF/FTC, TAF/FTC, or injectable cabotegravir) can be safely initiated based on patient preference and clinical factors

Common Pitfalls to Avoid

• Do not attempt to start oral PrEP concurrently with rifampin-containing TB treatment - the drug interaction will compromise PrEP efficacy
• Do not switch from rifampin to rifabutin in an HIV-negative patient solely to accommodate PrEP - this is not evidence-based and may compromise TB treatment 1
• Do not delay or modify TB treatment to accommodate PrEP initiation - active TB treatment is the immediate priority for morbidity, mortality, and public health outcomes
• Ensure the patient understands this is a temporary deferral (6 months), not a permanent contraindication to PrEP