efficacy and safety of fixed-dose combination of stavudine plus lamivudine plus nevirapine in the treatment of HIV infection in adults

Abstract

Objective: To determine the efficacy and safety of the fixed-dose combination of d4T/3TC/NVP in the treatment of antiretroviral naive HIV-infected Thai adults. Design: open label, single arm trial. Setting: Siriraj Hospital, which is the tertiary care center. Method: A baseline clinical assessment and blood test was done on 102 antiretroviral naive HIV-infected patients, who then received a fixed dose combination of d4T 30 mg (weight < 60 Kg) or 40 mg (weight is more than or equal to 60 Kg)/3TC150 mg/NVP 200 mg po q am and separated antiretroviral drugs consisting of d4T 30 mg (weight < 60 Kg) or 40 mg (weight is more than or equal to 60 Kg) po q pm + 3TC 150 mg po q pm for 2 weeks. A fixed dose combination of d4T 30 mg (weight < 60 Kg) or 40 mg (weight is more than or equal to 60 Kg)/3TC/NVP twice daily thereafter for 52 weeks. The patients were scheduled for follow-up visits at 2, 4, 8, 12, 24, 36 and 52 weeks at which time they were assessed clinically and evaluated for adverse events. A CD4 cell count and HIV-RNA assay were done at 12 weeks. Result: At week 12, the mean decrease in log HIV RNA was 2.87(0.76) log[subscript 10] copies/mL (P<0.001; 95%CI 2.70,3.03). Seventy three patients (86.9%) had HIV RNA <400 copies/mL by on-treatment analysis and 73.7% had HIV RNA <400 copies/mL by intent-to-treat analysis. Fifteen patients (88.2%) with baseline HIV RNA is less than or equal to 100,000 copies/mL and 58 patients (86.6%) with baseline HIV RNA > 100,000 copies/mL had viral load <400 copies/mL by on-treatment analysis (P=0.856). Fifteen patients (78.9%) with baseline HIV RNA is less than or equal to 100,000 copies/mL and 58 patients (72.5%) with baseline HIV RNA >100,000 copies/mL had viral load <400 copies/mL by intent-to-treat analysis (P=0.566). The mean (SD) CD4 cell count at week 12 was 131.6(83.0) cells/mm[superscript 3] (range 8-393). The mean (SD) increase in CD4 cell count from baseline was 73.7(55.5) cells/mm[superscript 3] (P<0.001). A total of 12% of the patients receiving d4T+3TC+NVP developed skin rashes. Hepatotoxicity was recognized in 6% of the patients. Conclusion: Fixed-dose combination of d4T+3TC+NVP is safe, well tolerated and effective in increasing CD4 cell counts and suppression of HIV RNA at 12 weeks in advanced HIV-infected patients in Thailand.