Efficacy, tolerance, and pharmacokinetics of the combination of stavudine, nevirapine, nelfinavir, and saquinavir as salvage regimen after ritonavir or indinavir failure.
The high rate of protease inhibitor treatment failure in clinical cohorts makes it necessary to define novel salvage therapies. In a prospective study of 31 HIV-infected patients included in a salvage regimen with stavudine, nevirapine, nelfinavir, and saquinavir, viral load decreased a median of 1.65 log(10) and 1.95 log(10) after 6 and 12 months of treatment, respectively, and 35 and 56% of patients had an HIV RNA level below 50 copies/ml at the same time points. At baseline, the mean number of mutations in the protease gene was 10 (2-19), and the V82A and L90M mutations were present in 54 and 21% of patients. The presence of the V82A mutation did not affect significantly the rate of response (36 vs. 38%), whereas the L90M mutation was associated with treatment failure (0 vs. 43%). Plasma trough levels of nelfinavir (NFV) and saquinavir (SQV), in a twice daily dosing regimen, were above the protein-corrected IC(95) in most patients despite the addition of an enzymatic inducer such as nevirapine, and peak levels were 2- and 5-fold increased with respect to standard doses. However, pharmacokinetics of saquinavir-hard gel capsule (SQV-hgc) did not improve significantly in the three times daily dosing regimen. In conclusion, the combination of stavudine, nevirapine, nelfinavir, and saquinavir increased plasma drug levels and produced an adequate virological response in patients who had failed indinavir or ritonavir therapy. This degree of response is not significantly decreased in the presence of genotypic mutations associated with indinavir/ritonavir (IDV/RTV) resistance.
Casado
J L
JL
Department of Infectious Diseases, Ramon y Cajal Hospital, 28034 Madrid, Spain. jcasado@hrc.insalud.es
Dronda
F
F
Hertogs
K
K
Sabido
R
R
Antela
A
A
Martí-Belda
P
P
Dehertogh
P
P
Moreno
S
S
D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D004338:Drug Combinations; D004352:Drug Resistance, Microbial; D004359:Drug Therapy, Combination; D005260:Female; D006678:HIV / Q000201:enzymology / Q000235:genetics; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D016333:HIV Protease / Q000235:genetics; D017320:HIV Protease Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D019469:Indinavir / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009154:Mutation; D019888:Nelfinavir / Q000493:pharmacokinetics / Q000627:therapeutic use; D019829:Nevirapine / Q000627:therapeutic use*; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D019438:Ritonavir / Q000627:therapeutic use; D019258:Saquinavir / Q000493:pharmacokinetics / Q000627:therapeutic use; D018119:Stavudine / Q000627:therapeutic use*; D017211:Treatment Failure; D019562:Viral Load
D019380:Anti-HIV Agents; D004338:Drug Combinations; D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D019469:Indinavir; D019829:Nevirapine; D018119:Stavudine; D016333:HIV Protease; D019888:Nelfinavir; D019258:Saquinavir; D019438:Ritonavir