Efficacy and safety of Efavirenz in HIV patients on Rifampin for tuberculosis

Abstract

Forty-nine AIDS patients, most of who were antiretroviral therapy (ARV) naive, with active tuberculosis, were treated with Rifampin 600 mg, Isoniazid 400 mg and Pirazinamide 2 g daily. They also received ARV, consisting of Efavirenz (600 mg/day) plus 2 NRTIs. All patients were prospectively followed for at least 24 months. Baselines were: male/female ratio 2:1, mean age 34.7 +/- 9.4 yrs; weight 51 +/- 9.0 kg, viral load 5.6 +/- 0.6 logs, CD4 cell count 101 +/- 128 cells/ mm3. Follow up mean values of data logs of VL and CD4+ cell /mm3 counts were: VL 1.7 and CD4+ 265; VL 1.3 and CD4+ 251; VL 1.4 and CD4+ 326 at 6, 12 and 24 months, respectively. Weight gain changes were: 5 +/- 9.9 +/- 12 and 21 +/- 16 kg respectively at 6, 12 and 24 months. A non-concomitant ARV regimen was introduced at least three weeks after TB treatment initiation. Severe adverse reactions included rash (two), toxic hepatitis (six), Immune Reconstitution Syndrome (seven), and four deaths. We conclude that Efavirenz at a daily dose of 600 mg is sufficient and safe to treat HIV/TB patients using a Rifampin containing regimen.

CYP2B6 G516T Polymorphism but Not Rifampin Coadministration Influences Steady-State Pharmacokinetics of Efavirenz in Human Immunodeficiency Virus-Infected Patients in South India

“…Although concomitant RMP administration lowered the peak concentration and exposure to EFV by about 18%, this did not seem to have any adverse impact on the immunological outcomes. This is in agreement with that suggested by others, who observed excellent clinical outcomes when giving EFV at 600 mg/day to patients receiving RMP (11,22,27,28). A study conducted with HIV-TB patients receiving EFV at 600 mg/day and RMP reported virological success in about 80% of the patients studied at 48 weeks of treatment (24).…”

“…The available pharmacokinetic data provide evidence of a 13 to 25% reduction in EFV levels when it is coadministered with RMP (20), which is lower than those of nevirapine (40%) and protease inhibitors (80 to 95%) (7). Although effective pharmacological, clinical, immunological, and virologic responses have been reported with a 600-mg dose of EFV (11,22,27,28), the adequacy of this dose during concomitant treatment with RMP remains a matter of debate. In fact, after reviewing the current literature, the FDA concluded that the available data are insufficient to support definitive dosing recommendations for the coadministration of EFV and RMP (10).…”

Clinical management of tuberculosis and HIV-1 co-infection

“…Several pharmacokinetic studies have found a 20-30% reduction in efavirenz levels when administered with rifampicin [166,167] and that, in general, increasing the efavirenz dose from 600 mg to 800 mg is effective and safe [166,168]. Conversely in cohort studies standard dose efavirenz has been given with rifampicin without compromised clinical efficacy [169][170][171]. A large cohort study conducted in South Africa showed no difference in rates of virological suppression when comparing patients on efavirenz-containing ART alone and those on efavirenz-containing ART and rifampicin-based TB treatment concurrently.…”

Tuberculose et VIH : drame de l’Afrique

“…Le traitement antirétroviral HAART (highly active antiretroviral therapy) doit-il être introduit aussitôt ou faut-il attendre quelques semaines ? Une expérience faite au Brésil suggère qu'attendre quatre semaines est préférable [7]. Outre ces problèmes logistiques, il faut savoir aussi qu'il existe des interactions médicamenteuses.…”