Triomune Bioequivalence With Innovators

Generic antiretroviral therapy is the mainstay of HIV treatment in resource-limited settings, yet there is little evidence confirming the bioequivalence of generic and brand name formulations. We compared the steady-state pharmacokinetics of Lamivudine, Stavudine and Nevirapine in HIV-infected subjects who were receiving a generic formulation (Triomune®) or the corresponding brand formulations (Epivir®, Zerit®, and Viramune®). An open-label, randomized, crossover study was carried out in 18 HIV-infected Ugandan subjects stabilized on Triomune-40. Subjects received Lamivudine (150 mg), Stavudine (40 mg), and Nevirapine (200 mg) in either the generic or brand formulation twice a day for 30 days, before switching to the other formulation. At the end of each treatment period, blood samples were collected over 12 h for pharmacokinetic analysis. The main outcome measures were the mean AUC0-12h and Cmax. Bioequivalence was defined as a geometric mean ratio between the generic and brand-name within the 90% confidence interval of 0.8-1.25.

Inclusion criteria

• HIV-infected men and non-pregnant women;
• On Triomune for at least 4 weeks;
• 18 years or greater;
• Residing within 15km of Kampala city center

Exclusion criteria

• Unable to sign or understand informed consent
• Concurrent medication known to interact with any of the components of Triomune
• Patients with active TB, malabsorption, nausea, emesis, abdominal discomfort, chronic diarrhoea, documented active clinically relevant hepatitis;
• Patients expected to change their drug regimen or dosage during the study
• Those planning to move out of Kampala in the next two months;
• Hemoglobin <7.0 mmol/l (men) or <6.5 mmol/l (women);
• Alanine aminotransferase or aspartate aminotransferase >5 times the upper limit of normal;
• Serum creatinine > 1.5 times the upper limit of normal