Pharmacokinetic Evaluation and Short-Term Activity of Stavudine, Nevirapine, and Nelfinavir Therapy in HIV-1???Infected Adults

Abstract

Evaluate pharmacokinetic interaction, short-term safety, and antiretroviral activity of stavudine (d4T), nevirapine (NVP), and nelfinavir (NFV) as combination HIV-1 therapy. Prospective, open-label study investigating the pharmacokinetic interactions between d4T, NVP, and NFV and documenting short-term tolerability and virologic and immunologic activity. Twenty-five HIV-1-infected adults, naive to nonnucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs), ≤6 months of d4T treatment, CD4 ≥100 cells/mm3, 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. 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/mm3. 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.