Pharmacokinetic evaluation and short-term activity of stavudine, nevirapine, and nelfinavir therapy in HIV-1-infected adults.
OBJECTIVE
Evaluate pharmacokinetic interaction, short-term safety, and antiretroviral activity of stavudine (d4T), nevirapine (NVP), and nelfinavir (NFV) as combination HIV-1 therapy.


METHODS
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.
Skowron
Gail
G
Division of Infectious Diseases, Roger Williams Medical Center, Providence, RI 02908, USA. Gail_Skowron@brown.edu
Leoung
Gifford
G
Hall
David B
DB
Robinson
Patrick
P
Lewis
Ronald
R
Grosso
Robert
R
Jacobs
Mark
M
Kerr
Bradley
B
MacGregor
Thomas
T
Stevens
Michael
M
Fisher
Alvan
A
Odgen
Richard
R
Yen-Lieberman
Belinda
B
D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D018791:CD4 Lymphocyte Count; D004347:Drug Interactions; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019888:Nelfinavir / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019829:Nevirapine / Q000493:pharmacokinetics* / Q000627:therapeutic use; D018119:Stavudine / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019562:Viral Load
D019380:Anti-HIV Agents; D019829:Nevirapine; D018119:Stavudine; D019888:Nelfinavir