Nearly half of the patients maintain undetectable HIV load after 1 year of therapy, although important immunological benefit can be obtained in a greater proportion of patients. These data suggest the use of the most potent antiretroviral therapy in pretreated patients with high HIV load, and the capacity of initial virological decline to predict the long-term outcome.
RTV/IDV 100/800 mg in a twice daily dosing regimen is associated with a significant virological response in patients with antiretroviral treatment failure. The correlation between plasma drug levels, toxicity, and response suggests the usefulness of individualized drug monitoring.
This data confirm the usefulness of phenotypic testing in guiding antiretroviral therapy in heavily pretreated patients. The number of active drugs and the line of salvage therapy are independent predictors of virological response, regardless of HIV load and the length of antiretroviral exposure.
Increased drug levels could overcome resistance and improve the response to a salvage regimen. We evaluate the inhibitory quotient (IQ, Ctrough/protein-binding corrected IC50) as a predictor of virological response in 52 patients included in two dual protease inhibitor (PI)-based salvage regimens. The HIV-RNA level decrease at 12 weeks was greater in patients who achieved an IQ greater than 1. The IQ could be useful to improve the virological response to a dual PI salvage regimen.
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.
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