Clinical trial NCT00196625: Salvage Therapy With Amprenavir, Lopinavir and Ritonavir in HIV-Infected Patients in Virological Failure.
Official title: Study on Safety and Efficacy of Salvage Therapy With Amprenavir, Lopinavir and Ritonavir 200 Mg/d or 400 Mg/d in HIV-Infected Patients in Virological Failure.ANRS 104 PUZZLE 1
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infections
Keywords: HIV infections
Salvage therapy
Amprenavir
Lopinavir
Ritonavir
Lead sponsor: French National Agency for Research on AIDS and Viral Hepatitis
Sponsor class: OTHER_GOV
First posted: 2005-09-20
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: HIV infected patients are treated with highly active antiretroviral therapy (HAART). Side effects and the great number of pills reduces adherence to the treatment, and induces therapeutic failure. In order to maintain efficacy of HAART, new combination is evaluated. The aim of the study is to compare the antiviral efficacy of this salvage therapy combining lopinavir and amprenavir with 200 mg/d or 400 mg/d ritonavir, together with nucleoside reverse transcriptase inhibitors, over a 26-week period in HIV-infected patients in whom multiple antiretroviral regimens had failed.

Detailed description: HIV infected patients are treated with highly active antiretroviral therapy (HAART). Side effects and the great number of pills reduces adherence to the treatment, and induces therapeutic failure. In order to maintain efficacy of HAART, new combination is evaluated. The aim of the study is to compare the antiviral efficacy of this salvage therapy combining lopinavir and amprenavir with 200 mg/d or 400 mg/d ritonavir, together with nucleoside reverse transcriptase inhibitors (NRTI), over a 26-week period in HIV-infected patients in whom multiple antiretroviral regimens had failed. 100 patients with CD4 cell count below 300/mm3 and plasma HIV RNA over 30,000 copies/ml are to be included in four groups: amprenavir, lopinavir, NRTI, with ritonavir 200 mg.d or not (patients previously treated by additional ritonavir 200 or 400 mg/d).

Eligibility criteria: Inclusion Criteria:

* Documented HIV infection
* CD4 cell count below 300/mm3
* Plasma HIV RNA over 30,000 copies/ml
* Previously treated with 2 protease inhibitors and 1 non nucleoside analogue (except amprenavir, lopinavir)
* Written informed consent

Exclusion Criteria:

* Biological abnormalities
* Pregnancy
* Alcool abuse
* History of pancreatitis, hepatic failure
* Acute HIV related infection
* Chemotherapy

Primary outcomes:
measure: Mean change of VIH RNA between week 0 and week 26
Secondary outcomes:
measure: Disease progression
measure: CD4 cell count
measure: Safety
measure: Pharmacokinetics
measure: Genotypic resistance
Other outcomes:
Locations:
Study officials:
affiliation: Service des Maladies Infectieuses et Tropicales, Hôpital Saint-Antoine, Paris, France
name: Gilles Raguin, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: INSERM U593, Bordeaux, France
name: Genevieve Chene, MD, PhD
role: STUDY_DIRECTOR
References:
citation: Raguin G, Chene G, Morand-Joubert L, Taburet AM, Droz C, Le Tiec C, Clavel F, Girard PM; Puzzle 1 Study Group. Salvage therapy with amprenavir, lopinavir and ritonavir 200 mg/d or 400 mg/d in HIV-infected patients in virological failure. Antivir Ther. 2004 Aug;9(4):615-25.
citation: Taburet AM, Raguin G, Le Tiec C, Droz C, Barrail A, Vincent I, Morand-Joubert L, Chene G, Clavel F, Girard PM. Interactions between amprenavir and the lopinavir-ritonavir combination in heavily pretreated patients infected with human immunodeficiency virus. Clin Pharmacol Ther. 2004 Apr;75(4):310-23. doi: 10.1016/j.clpt.2003.12.013.