A 34-year-old man with HIV infection (CD4 count 175 cells/μL) presents with a 3-week history of productive cough, fever, and night sweats. Chest X-ray reveals bilateral upper lobe infiltrates with cavitation. Sputum smear microscopy is positive for acid-fast bacilli. He is initiated on a standard four-drug tuberculosis regimen (rifampicin, isoniazid, pyrazinamide, and ethambutol) and continues his current efavirenz-based antiretroviral therapy. Laboratory values: ALT 42 U/L, AST 38 U/L, CD4 count 175 cells/μL, viral load 45,000 copies/mL. Vital signs are stable. Two weeks into treatment, plasma efavirenz concentrations fall 40% below the therapeutic range despite consistent medication adherence and normal renal/hepatic function. Which of the following best explains this pharmacokinetic interaction?

1. A)Isoniazid competitively inhibits CYP2B6, the primary metabolic enzyme for efavirenz
2. B)Pyrazinamide increases gastric pH, reducing efavirenz absorption from the gastrointestinal tract
3. C)Rifampicin induces CYP3A4 and CYP2B6, increasing efavirenz hepatic metabolism and clearanceGABARITO
4. D)Ethambutol forms a chelation complex with efavirenz, reducing its bioavailability
5. E)Tuberculosis-induced hepatic inflammation impairs efavirenz protein binding and renal excretion