Saquinavir/Ritonavir in Single Therapy as Maintenance Treatment

Study Overview
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Brief Summary
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Study the efficacy of Saquinavir/Ritonavir when given in single therapy as maintenance therapy, compared to standard HAART therapies.

Detailed Description
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Different therapeutic strategies have been investigated to improve adherence to treatment and reduce toxicity. Both the reduction in the number of doses and the number of daily tablets have led to an improvement in therapeutic compliance. Similarly, the administration of new treatment regimens with a reduced number of tablets a day and without NTRI may be clinically useful in improving compliance with HAART and limiting NTRI-associated toxicity. These would comprise combinations of a PI, boosted with ritonavir, plus a non-Nucleoside and single therapy with PIs boosted with ritonavir. In this regard, the results obtained with lopinavir/ritonavir and with atazanavir/ritonavir are very promising and open up a possible channel of research with other PIs boosted with low doses of ritonavir. There are other PIs whose antiretroviral efficacy has also been demonstrated, such as saquinavir, but whose economic cost is much lower. Furthermore, saquinavir has a low toxicity profile, and the availability of saquinavir 500 mg facilitates comfortable administration, since it makes it possible to reduce the number of daily tablets to more than half. Moreover, it is important to take into account that the incidence of mutations that confer resistance to saquinavir on patients that fail on combinations including this PI is very low, which makes it possible to reuse the drug in future treatment regimens or salvage patients with other PI All these characteristics (high intrinsic potency, low number of tablets, low toxicity, low potential of selection of resistant viral strains in combination with ritonavir, and low economic cost) make single therapy with the new formulation of saquinavir, boosted with low doses of ritonavir, a possible therapeutic option as maintenance strategy in HIV-infected patients with maintained suppression of the viral load.

Official Title
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Open-label, Comparative and Randomised Pilot Study to Evaluate the Efficacy and Safety of Saquinavir/Ritonavir in Single Therapy vs Standard HAART Therapy as Maintenance Therapy.

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: Saquinavir/Ritonavir : 2 capsules (500 mg) / 12 hours


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients infected by HIV-1 (at least one documented positive Western-Blot). Age > 18 years. Patients on antiretroviral treatment (standard HAART therapy) for at least six months. HIV-1 plasma viral load <50 copies/mL (documented in at least two determinations performed over the six months prior to the inclusion visit). Patients without evidence of previous virological failure to IP Absence of opportunistic infections and/or tumours in the three months prior to inclusion. Subject able to follow the treatment period, without any suspicion of poor adherence during previous antiretroviral treatments. Signature of the informed consent. Exclusion Criteria: Suspicion of unsuitable antiretroviral treatment compliance. Documented existence of any of the primary mutations in the protease gene or 3 or more of the following: L10F/I/R/V, K20M/R, M36I/V, I54L/T/V, L63P, A71T/V , V82A/F/T/S, I84A/V OR L90M. Known allergic hypersensitivity to any of the investigational drugs or any similar drug. Hepatic tests (AST, ALT, GGT) > or equal to 5 times the upper limit of normality during the three months prior to the screening visit Presence of renal impairment (creatinine > or equal to 1.5 times the upper limit of normality). Pregnancy or breastfeeding. Refusal to use reliable contraceptive methods during the study period. Participation in another clinical trial wich entail the antiretroviral treatment modification.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>Saquinavir (Invirase): 2 capsules (500 mg) / 12 hours | Drug: Saquinavir/Ritonavir : 2 capsules (500 mg) / 12 hours<br>* Saquinavir/Ritonavir: 2 capsules (500 mg) / 12 hours<br>* Other names: Invirase;|
| No Intervention: 2<br>IP o NNUCS + 2 NUCS as a HAART therapy . | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Virological response: Viral Load |  | weeks 24 and 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CD4 and CD8 lymphocyte count. |  | weeks 24 and 48 | 
| Physical Exploration: including weight, height, index waist/hip (the abdominal perimeter is measured between the last floating rib and the iliac crest), assessment of changes in body fat distribution,... |  | weeks 24 and 48 | 
| Karnofsky Index. |  | weeks 24 and 48 | 
| Adverse events. |  | during the 48 weeks of follow-up | 
| Trough plasma concentrations of Saquinavir. |  | during the 48 weeks of follow-up | 
| Lipid study in plasma (total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides) |  | during the 48 weeks of follow-up | 
| Serology for Hepatitis B and C virus. |  | at baseline visit | 
| Assessment of treatment adherence. |  | at baseline and weeks 4, 12, 24, 36 and 48 | 
| Assessment of quality of life (by means of the MOS-HIV questionnaire). |  | at baseline and weeks 4, 12, 24, 36 and 48 | 
| Genotype if virological failure. |  | at any time of study if it is necessary | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Saquinavir/ritonavir, Single therapy, Virological efficacy, Safety, HIV-1