Pharmacokinetic evaluation and short-term activity of stavudine, nevirapine, and nelfinavir therapy in HIV-1-infected adults

Abstract

Objective: Evaluate pharmacokinetic interaction, short-term safety, and antiretroviral activity of stavudine (d4T), nevirapine (NVP), and nelfinavir (NFV) as combination HIV-1 therapy.

Design: Prospective, open-label study investigating the pharmacokinetic interactions between d4T, NVP, and NFV and documenting short-term tolerability and virologic and immunologic activity.

Methods: Twenty-five HIV-1-infected adults, naive to nonnucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs), < or = 6 months of d4T treatment, CD4 > or = 100 cells/mm, and viral load > = 5,000 copies/mL enrolled. All received NFV 750 mg 3 times daily and d4T 30-40 mg twice daily for 1 week, then added NVP at 200 mg once daily for 2 weeks and 200 mg twice daily thereafter. Steady-state pharmacokinetic parameters of NFV, AG1402 (metabolite of NFV), and d4T were compared before and after the addition of NVP.

Results: No statistically significant changes in NFV or d4T pharmacokinetics were observed following the addition of NVP. Levels of AG1402 were suppressed 60-70%. Drug-related adverse events were seen at expected rates. At day 36, median viral load suppression was 2.0 log10 and absolute CD4 count increased by 111 cells/mm.

Conclusions: NVP administration did not significantly affect the steady-state pharmacokinetic parameters of NFV or d4T. The combination of d4T, NVP, and NFV induced rapid suppression of HIV-1 viral load and rises in CD4 cell count.