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

French National Agency for Research on AIDS and Viral Hepatitis

Status: Terminated

Conditions: HIV Infections

Treatments: Drug: nelfinavir; Drug: lopinavir/r; Drug: indinavir; Drug: ritonavir

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00122590

ANRS111 COPHAR 2

Details and patient eligibility

About

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.

Full 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.

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)