Efficacy, safety and pharmacokinetic of once-daily boosted saquinavir ide reverse transcriptase inhibitors in real life: a multicentre prospective study

• Published in: AIDS research and therapy 2010-03, Vol.7, p.5
• Main Authors: López-Cortés, Luis F, Viciana, Pompeyo, Ruiz-Valderas, Rosa, Pasquau, Juan, Ruiz, Josefa, Lozano, Fernando, Merino, Dolores, Vergara, Antonio, Terrón, Alberto, González, Luis, Rivero, Antonio, Muñoz-Sanz, Agustin
• Format: Article
• Language: English
• Subjects: Analysis; Diagnosis; DNA polymerases; Dosage and administration; Drug therapy; Hepatitis C; Pharmacokinetics; Properties; Reverse transcriptase inhibitors; Saquinavir
• ISSN: 1742-6405; 1742-6405
• DOI: 10.1186/1742-6405-7-5

Background Ritonavir-boosted saquinavir (SQVr) is nowadays regarded as an alternative antiretroviral drug probably due to several drawbacks, such as its high pill burden, twice daily dosing and the requirement of 200 mg ritonavir when given at the current standard 1000/100 mg bid dosing. Several once-daily SQVr dosing schemes have been studied with the 200 mg SQV old formulations, trying to overcome some of these disadvantages. SQV 500 mg strength tablets became available at the end of 2005, thus facilitating a once-daily regimen with fewer pills, although there is very limited experience with this formulation yet. Methods Prospective, multicentre study in which efficacy, safety and pharmacokinetics of a regimen of once-daily SQVr 1500/100 mg plus 2 NRTIs were evaluated under routine clinical care conditions in either antiretroviral-naïve patients or in those with no previous history of antiretroviral treatments and/or genotypic resistance tests suggesting SQV resistance. Plasma SQV trough levels were measured by HPLV-UV. Results Five hundred and fourteen caucasian patients were included (47.2% coinfected with hepatitis C and/or B virus; 7.8% with cirrhosis). Efficacy at 52 weeks (plasma RNA-HIV [less than]50 copies/ml) was 67.7% (CI.sub.95 : 63.6 - 71.7%) by intention-to-treat, and 92.2% (CI.sub.95 : 89.8 - 94.6%) by on-treatment analysis. The reasons for failure were: dropout or loss to follow-up (18.4%), virological failure (7.8%), adverse events (3.1%), and other reasons (4.6%). The high rate of dropout may be explained by an enrollement and follow-up under routine clinical care condition, and a population with a significant number of drug users. The median SQV Cmin (n = 49) was 295 ng/ml (range, 53-2172). The only variable associated with virological failure in the multivariate analysis was adherence (OR: 3.36; CI95, 1.51-7.46, p = 0.003). Conclusions Our results suggests that SQVr (1500/100 mg) once-daily plus 2 NRTIs is an effective regimen, without severe clinical adverse events or hepatotoxicity, scarce lipid changes, and no interactions with methadone. All these factors and its once-daily administration suggest this regimen as an appropriate option in patients with no SQV resistance-associated mutations.