Safety, efficacy and pharmacokinetics of ritonavir 400 mg - saquinavir 400 mg and rifampicin combined therapy in HIV naive patients with tuberculosis.
Introduction: Treatment of tuberculosis (TB) and AIDS with rifampicin and ritonavir -saquinavir (rtv-sqv) is recommended in current guidelines although this association is not well studied in literature. Our aim is to access drug concentration, efficacy and safety of concomitant use of rifampicin and antiretroviral regimens containing rtv-sqv (400-400) in TB-HIV naive patients.
Methods: AIDS patients with TB diagnosis were enrolled (n=20). At day 0, TB treatment was introduced. At day 30, HAART (2 nucleoside analogs and rtv-sqv 400/400 mg bid) was initiated. Pharmacokinetics from serial blood samples was assayed with a validated reversed-phase HPLC method before HAART introduction, after 30 days of therapy and at the end of study (without rifampicin). Clinical evaluation was performed monthly and recorded vital signs, weight, karnofsky score and adverse events (AE). CD4 counts, viral load (VL) and genotyping test were collected at baseline, D30 and D180. Primary endpoints were: drug concentration and viral load at D180 (<80 copies). Secondary endpoints were the presence of grade 3 and 4 AE, clinical improvement, CD4 counts, and genotypic resistance to rtv-sqv
Results: We included 20 patients with TB-HIV diagnosis. Mean baseline CD4 counts was 152 cells/ mm3 (±146) and baseline VL was 5,34 log (±0,4). During the study 15 patients dropped out, 14 because of AE (hepatic and gastrointestinal were the most frequents). One patient (among 5) presented VL<80 copies at D180. All but one increased baseline CD4 counts. No genotypic resistance was detected. Clinical improvement was evident in all (n=5) patients who tolerated the therapy. A decrease in AUC and an extended elimination half-life of rtv-sqv was observed during rifampicin therapy but concentrations were in the therapeutic range.
Conclusions: Although therapeutic levels of the studied drugs were achieved and VL reduced we do not recommend this regimen for naive patients because AE are the major cause of treatment abandon.
The 3rd IAS Conference on HIV Pathogenesis and Treatment
"CavalcantiRollaV., et al.
Safety, efficacy and pharmacokinetics of ritonavir 400 mg - saquinavir 400 mg and rifampicin combined therapy in HIV naive patients with tuberculosis..
The 3rd IAS Conference on HIV Pathogenesis and Treatment: