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Preliminary safety results of co-administration of nevirapine (NVP) or efavirenz (EFV), and rifampicin (RMP) in HIV-tuberculosis (TB) co-infected patients in Maputo (Mozambique): CARINEMO-ANRS 12146 Trial
N.B. Bhatt1, E. Baudin2, I.V. Jani1, L. Ciaffi3, M. Luggli3, R. Bastos4, P. Samo Gudo5, D. Arakaki6, C. Michon7, A. Calmy8,9, M. Bonnet10, and the ANRS 12146 Study Group
1National Institute of Health, Department of Immunology, Maputo, Mozambique, 2Epicentre, Paris, France, 3Médecins sans Frontières, Geneva, Switzerland, 4Maputo Central Hospital, Department of Dermatology, Maputo, Mozambique, 5Ministry of Health, National Tuberculosis Program, Maputo, Mozambique, 6The International Center for AIDS Care and Treatment Programs (ICAP), Maputo, Mozambique, 7Annecy Hospital, Paris, France, 8Access Campaign for Essential Medicine, Médecins sans Frontières, Geneva, Switzerland, 9Geneva University Hospital, Geneva, Switzerland, 10Epicentre, Geneva, Switzerland
Background: Nevirapine (NVP) based antiretroviral therapy is 1st line treatment in sub-Saharan countries. In TB-HIV co-infected patients, co-administration with RMP may result in sub-therapeutic NVP concentration. Skipping NVP 2 weeks leading dose in patients under RMP could overcome this problem but increase toxicity.
Methods: We conduct a prospective phase 3, randomized, open-label non-inferiority trial comparing 48 weeks virological suppression and safety of NVP (400mg without leading dose) vs EFV (600mg daily) combined to lamivudine-stavudine in HIV-TB co-infected patients. Patients with CD4< 250 cell/mm3 and active TB are randomized 4 weeks after starting TB treatment (baseline). Clinical assessment and alaminotransferrase (ALT) measurement assess the safety. Recruitment of 570 patients started in November 2007 and will continue until end of 2009. Overall preliminary safety results are presented.
Results: Until December 2008, 236 patients were enrolled (60% male and 73.3% with pulmonary TB), of those 4.7% discontinued treatment due to death (6), consent withdrawal (3) and lost of follow-up (1). At baseline, median (Inter Quartile Range) age, weight, CD4+ cell-count and ALT were 34 years (28-41), 53.0 Kg (47.9-58.9), 85.0 cells/mm3 (44.0-148.0) and 22.2 UI/L (14.0-36.4), respectively. Active Hepatitis B infection was found in 26.6% (34/128). A total of 26 SAE were declared: 6 anemia, 5 infectious diseases, 3 immune reconstitution syndromes, 3 hepatitis, 3 psychosis, 2 opportunistic infections, 1 diarrhea, 1 acute aphasia, 1 anasarc and 1 agranulocytosis. Grade≥2 (>2.5UNL) and grade≥3 (>5UNL) ALT increase was found in 14% and 4.7% of cases, respectively. Five (2.1%) patients permanently interrupted treatment due to hepatitis. Skin related adverse events were reported in 19.9% but none were severe or leaded to drug discontinuation.
Conclusions: The absence of severe rash, the relatively low number of severe hepatitis and definitive treatment interruptions due to hepatitis are reassuring but need to be further confirmed.
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