Evaluation of Therapeutic Drug Monitoring of Protease Inhibitors on Virologic Success and Tolerance of Highly Active Antiretroviral Therapy (HAART)

NCT ID: NCT00122590

Last Updated: 2005-08-01

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 115 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-07-31
• Study Completion Date: 2005-03-31

Brief Summary

This Cophar2 study is a trial which evaluates repeated early therapeutic drug monitoring, from weeks 2 to 24, after the initiation of HAART including either indinavir/r, lopinavir/r or the new 625 mg formulation of nelfinavir twice-a-day (bid). If trough concentrations were out of the range given for each protease inhibitor (PI), the PI dose was adjusted.

Detailed Description

Because of the large pharmacokinetic inter-patient variability of protease inhibitors (PI), therapeutic drug monitoring (TDM) of protease inhibitor (PI) has been proposed to improve efficacy and tolerance of PI-containing HAART. The objective of the Cophar2 trial is to evaluate the feasibility and the impact of an early therapeutic drug monitoring in PI-naive HIV-1 infected patients in order to warrant virological success and safety of HAART.

It is a prospective, open, multicenter trial with repeated early TDM (weeks 2, 8 or 16, 24) after the initiation of HAART including either indinavir/r (IDV), lopinavir/r (LPV) or the new 625 mg formulation of nelfinavir (NFV) bid. It was planned to include 99 PI-naïve HIV-1 infected patients over 18 years old, 33 for each PI. Concentrations were measured by HPLC in each center. If trough concentrations were out of the range of 150-500, 2500-7000 or 1500-5500 ng/ml for IDV, LPV and NFV respectively, the PI doses were adjusted possibly more than once during the first 24 weeks of follow-up. Adjustments were done by steps of one pill (200, 133/33 or 250 mg for IDV, LPV/r or NFV, respectively) bid. Failure of the strategy was defined by either two consecutive viral loads over 200 copies/ml between weeks 16 and 48, or a validated PI-related adverse event grade III or IV or a grade II diarrhoea or renal lithiasis. Patients without adverse events before week 16 were defined as assessable if they had at least the virological assessment of week 16.

Conditions

HIV Infections

Keywords

protease inhibitors; nelfinavir; lopinavir; indinavir; Pharmacokinetics

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

nelfinavir

Intervention Type: DRUG

lopinavir/r

Intervention Type: DRUG

indinavir

Intervention Type: DRUG

ritonavir

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Patients infected with HIV-1
• Needing an antiretroviral treatment according to standard of care
• HIV viral load greater than 1000 copies/ml
• Beginning a treatment containing a PI (indinavir with or without ritonavir, nelfinavir, lopinavir + ritonavir) and 2 reverse transcriptase inhibitors
• PI-naive
• Antiretroviral treatment-naive or already treated with reverse transcriptase inhibitors but if the viral genotypic test does not show more than 2 major mutations (including T215Y/F, Q151M, M184V/I, V75M/S, L74V) and if 3 nucleoside analogues are still active except for didanosine.

Exclusion Criteria

• Pregnant women and nursing mothers
• Acute HIV infection
• Diabetes
• Renal insufficiency with creatinine clearance below 30 ml/min
• Cardiac insufficiency
• Hepatic insufficiency with TP below 60%
• Treatment with known interactions with PI
• Chemotherapy against Kaposi's sarcoma, lymphoma, neoplasia
• Treatment containing interferon (INF) or interleukin-2 (IL2) or HIV- immune vaccine
• Treatment with hypolipemic drugs
• Laxative treatment
• Previous renal colic
• Diarrhoea with more than 5 stools/day since one week

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: collaborator

French National Agency for Research on AIDS and Viral Hepatitis

OTHER_GOV

Sponsor Role: lead

Principal Investigators

Dominique Salmon, MD

Role: PRINCIPAL_INVESTIGATOR

Service de Medecine Interne Hopital Cochin Paris

France Mentre, MD

Role: STUDY_CHAIR

Inserm EMI 03 57

Locations

Service de Medecine Interne Hopital Cochin

Paris, , France

Countries

France

Other Identifiers

ANRS111 COPHAR 2

Identifier Type: -

Identifier Source: org_study_id