Background: Drug-drug interaction is still a challenge to design the ideal TB-Rx in AIDS patients (pts) receiving ARV therapy. Several reports have documented toxicities of both treatment together; also pharmacokinetics study of Rifampin recently suggest no substantially change in the presence of Efavirenz. On the other hand, the minimal effective Efavirenz plasma concentration that assure virological success is not known. Herein we report the efficacy and safety of ARV-EFZ containing regimen administered for the treatment of HIV-infected pt during the treatment of active tuberculosis.

Methods: Forty-four (44) HIV infected pts with active tuberculosis (pulmonary TB 20 pts extrapulmonary 24 pts), mostly ARV naive, were enrolled in an prospective open label protocol to evaluate the safety and efficacy of co-administration of tuberculosis regimen containing Rifampin 600mg, Isoniazid 400mg (9 months [mos]) and Pyrazinamide 2g (2 initial mo) and ARV therapy regimen containing 2 NUCs and EFZ (600mg/day). Clinical evaluation and laboratory profile including acid fast bacilli, CD4/CD8 counts and viral load. Pts were followed up to 36 mos.

Results: Male/female ratio = 2:1 (30/14), mean age was 33.8 ±8.7 yr (19–61), weight 51 ±9.0 Kg (35–64) and baseline viral load (VL) was 6.0 ±6.4 log (1.5–7.0) a CD4 cell count/mm³ was 106 ±132. After 3 mos, Rx VL decrease to 3.8 ±2.1 log with 16/22 below the detection limit, and CD4 cell counts increase 3.5 folds. VL continue to decrease and CD4⁺ counts continuing to raise until 24 mos observation: means values 6 mos VL = 1.7 log and CD4⁺ = 287; 12 mos VL = 1.3 log CD4⁺ = 255 and 24 mos VL = 1.4 log CD4⁺ = 341 cell count/mm³. The weight gain was at 6 mos in average of 5 ±9; 12 mos 9 ± 12; and 24 mos 21 ±16 Kg. Severe adverse reactions included rash (1) toxic hepatitis (4), and Immune Reconstitution Syndrome was noted in 5 patients, including fever, limphadenopaty, and H. zoster. Three (3) pts died during the first month of therapy, 2 of them with associated histoplasmosis and 1 with renal failure associated with the treatment.

Conclusions: Overall, 80% (35/44) had resolution of the Tb and respond well to the ARV Rx. Of the 9 failure pts, 6 abandoned the treatment before 6 mos of therapy. Efavirenz 600mg daily dose is sufficient to treat HIV/TB pt with Rifampin containing regimen. More clinical/pharmacological studies are warranted.