Efficacy, safety and pharmacokinetic of once-daily boosted saquinavir (1500/100 mg) together with 2 nucleos(t)ide reverse transcriptase inhibitors in real life: a multicentre prospective study

López-Cortés, Viciana Pompeyo, Ruiz-Valderas Rosa, Pasquau Juan, Ruiz Josefa, Lozano Fernando, Merino Dolores, Vergara Antonio, Terrón Alberto, González Luís, Rivero Antonio, Muñoz-Sanz Agustin

Description

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 <50 copies/ml) was 67.7% (CI 95 : 63.6 - 71.7%) by intention-to-treat, and 92.2% (CI 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.

Informations

• Publié par: biomed
• Publié le: 01 janvier 2010
• Nombre de lectures: 2
• Langue: English

Extrait

LópezCortéset al.AIDS Research and Therapy2010,7:5 http://www.aidsrestherapy.com/content/7/1/5

R E S E A R C H

Open Access

Efficacy, safety and pharmacokinetic of oncedaily boosted saquinavir (1500/100 mg) together with 2 nucleos(t)ide reverse transcriptase inhibitors in real life: a multicentre prospective study 1* 1 1 2 3 4 Luis F LópezCortés , Pompeyo Viciana , Rosa RuizValderas , Juan Pasquau , Josefa Ruiz , Fernando Lozano , 5 6 7 8 9 10 Dolores Merino , Antonio Vergara , Alberto Terrón , Luis González , Antonio Rivero , Agustin MuñozSanz

Abstract 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 <50 copies/ml) was 67.7% (CI 95 : 63.6  71.7%) by intentionto treat, and 92.2% (CI 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.

Background Saquinavir was the first protease inhibitor (PI) commer cially available for the treatment of patients with HIV infection. Its oral bioavailability is markedly increased when concomitantly administered with low dose retai ner, which allows for reduced dosing frequency and

* Correspondence: [e-mail] 1 Servicio de Enfermedades Infecciosas, Hospitales Universitarios Virgen del Rocío, Instituto de Biomedicina de Sevilla, Seville, Spain

dosage. Ritonavirboosted saquinavir (SQVr) at the stan dard dosing of 1000/100 mg twice daily has shown as effective as ritonavirboostedlopinavir, although requir ing a higher pill burden when prescribed as the 200 mg hard or softgel capsules, which frequently leads to a bad compliance and high rates of therapy discontinua tion [1,2]. In several guidelines for the treatment of HIV1infected patients, SQVr has remained as an alter native antiretroviral drug, probably due to its high daily

© 2010 LópezCortés et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.