Clinical trial NCT00122668: Evaluation of the Occurrence of Lipoatrophy in HIV-1 Infected Naive Patients
Official title: Randomized Comparative Study Evaluating the Rate of Occurrence of a Lipoatrophy Syndrome in ARVnaive HIV-1 Infected Patients Receiving NRTI-Sparing Antiretroviral Regimen (Hippocampe - ANRS 121)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: HIV Infections
HIV-Associated Lipodystrophy Syndrome
Keywords: HIV Protease Inhibitors
HIV-Associated Lipodystrophy Syndrome
HIV infections
Lead sponsor: French National Agency for Research on AIDS and Viral Hepatitis
Sponsor class: OTHER_GOV
First posted: 2005-07-22
Enrollment: 112
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: The aim of this randomized study is to compare the occurrence of lipoatrophy in HIV-1 infected, naive patients receiving either a nucleoside reverse transcriptase inhibitor (NRTI)-sparing antiretroviral therapy with non-nucleoside reverse transcriptase inhibitor (NNRTI) and boosted protease inhibitor (PI), or a standard antiretroviral therapy with 2 NRTI plus either PI or NNRTI. Lipoatrophy is evaluated by measurement of fat volume by computed tomography (CT)-scan and DEXA (Dual Energy X-ray Absorptiometry).

Detailed description: The study compare the rate of occurrence of lipoatrophy in ARVnaive HIV-1 infected patients receiving either a NRTI-sparing antiretroviral therapy with NRTI and boosted PI,or a standard antiretroviral therapy with 2 NRTI plus PI or NNRTI.

Patients were randomized (2:1:1) to either PI+NNRTI (Gp1) or standard therapy, 2NRTI+ either PI (Gp2) or + NNRTI (Gp3). The study-treatment were lopinavir/r 100/400mg bid or indinavir/r 100/400mg bid for PI-class, for NNRTI-class, efavirenz or nevirapine and all NRTIs except D4T and DDC at usual dosage.

Lipoatrophy is evaluated by evolution of subcutaneous fat in the limbs measured by DEXA (Dual Energy X-ray Absorptiometry)and CT-scan of the thighs between baseline and W96.

Eligibility criteria: Inclusion Criteria:

* Confirmed HIV-1-infected diagnosis
* Naive of antiretroviral treatment
* Plasma viral load (VL) over 5000 copies/ ml
* CD4 count below or equal to 350/mm3 or CD4 over 350/mm3 and VL over or equal to 100 000 copies/ml
* Written, informed consent after approval by the local human research ethics committee

Exclusion Criteria:

* Acute opportunistic infection
* Pregnancy or breast feeding
* Cytotoxic systemic chemotherapy except for Kaposi sarcoma
* Patient infected with B or C hepatitis requiring specific treatment at the beginning of the study
* Polynuclear neutrophils below 750/mm3
* Hemoglobin below 8 g/dl
* Platelets below 20 000/mm3
* Creatinine level over 1.5 (upper normal) UN
* ASAT, ALAT, bilirubin level over 3 UN

Primary outcomes:
measure: Evolution of subcutaneous fat in the limbs measured by DEXA and CT-scan of the thighs between baseline and Week 96
Secondary outcomes:
measure: During the study until 96 weeks
measure: Viro-immunologic efficacy: Proportion of patients with a plasma viral load below 400 and 50 copies/ml
measure: Evolution of viral load
measure: Evolution of CD4 lymphocytes
measure: Evaluation of clinical safety
measure: Evaluation of lipohypertrophic syndrome
measure: Evaluation of glucidic and lipids metabolic profile
measure: Evaluation of mitochondrial toxicity
measure: Evaluation of bone toxicity by measurement of bone density
measure: Evaluation of plasma trough concentration of protease inhibitors and non nucleoside reverse transcriptase inhibitors
measure: Evaluation of intracellular concentration of nucleoside reverse transcriptase inhibitors
measure: Evolution of quality of life using the World Health Organization Quality of Life in persons with HIV Brief Form (WHO-QOL-HIV BREF)
Other outcomes:
Locations:
city: Paris
country: France
facility: Service des Maladies infectieuses et Tropicales Hopital Pitie Salpetriere
Study officials:
affiliation: Service des Maladies infectieuses et Tropicales, Hopital Pitie Salpetriere, Paris
name: Claudine Duvivier, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: INSERM U 720
name: Dominique Costagliola
role: STUDY_CHAIR
References:
citation: Soulie C, Assoumou L, Ghosn J, Duvivier C, Peytavin G, Ait-Arkoub Z, Molina JM, Costagliola D, Katlama C, Calvez V, Marcelin AG. Nucleoside reverse transcriptase inhibitor-sparing regimen (nonnucleoside reverse transcriptase inhibitor + protease inhibitor) was more likely associated with resistance comparing to nonnucleoside reverse transcriptase inhibitor or protease inhibitor + nucleoside reverse transcriptase inhibitor in the randomized ANRS 121 trial. AIDS. 2009 Jul 31;23(12):1605-8. doi: 10.1097/QAD.0b013e32832d9031.
citation: Duvivier C, Kolta S, Assoumou L, Ghosn J, Rozenberg S, Murphy RL, Katlama C, Costagliola D; ANRS 121 Hippocampe study group. Greater decrease in bone mineral density with protease inhibitor regimens compared with nonnucleoside reverse transcriptase inhibitor regimens in HIV-1 infected naive patients. AIDS. 2009 Apr 27;23(7):817-24. doi: 10.1097/QAD.0b013e328328f789.
citation: Duvivier C, Ghosn J, Assoumou L, Soulie C, Peytavin G, Calvez V, Genin MA, Molina JM, Bouchaud O, Katlama C, Costagliola D; ANRS 121 study group. Initial therapy with nucleoside reverse transcriptase inhibitor-containing regimens is more effective than with regimens that spare them with no difference in short-term fat distribution: Hippocampe-ANRS 121 Trial. J Antimicrob Chemother. 2008 Oct;62(4):797-808. doi: 10.1093/jac/dkn278. Epub 2008 Jul 18.