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 m akes 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, respectivel y, and 35 and 56% of patients had an HIV RNA level below 50 copies/ml at th e same time points. At baseline, the mean number of mutations in the protea se gene was 10 (2-19), and the V82A and L90M mutations were present in 54 a nd 21% of patients, The presence of the V82A mutation did not affect signif icantly the rate of response (36 vs. 38%), whereas the L90M mutation was as sociated with treatment failure (0 vs. 43%), Plasma trough levels of nelfin avir (NFV) and saquinavir (SQV), in a twice daily dosing regimen, were abov e the protein-corrected IC95 in most patients despite the addition of an en zymatic inducer such as nevirapine, and peak levels were 2- and 5-fold incr eased with respect to standard doses. However, pharmacokinetics of saquinav ir-hard gel capsule (SQV-hgc) did not improve significantly in the three ti mes daily dosing regimen. In conclusion, the combination of stavudine, nevi rapine, nelfinavir, and saquinavir increased plasma drug levels and produce d an adequate virological response in patients who had failed indinavir or ritonavir therapy. This degree of response is not significantly decreased i n the presence of genotypic mutations associated with indinavir/ritonavir ( IDV/RTV) resistance.