Evaluation of Therapeutic Drug Monitoring of Protease Inhibitors on Virologic Success and Tolerance of Highly Active Antiretroviral Therapy (HAART)
![]() |
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT00122590 |
Recruitment Status :
Terminated
First Posted : July 22, 2005
Last Update Posted : August 1, 2005
|
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
Condition or disease | Intervention/treatment | Phase |
---|---|---|
HIV Infections | Drug: nelfinavir Drug: lopinavir/r Drug: indinavir Drug: ritonavir | Not Applicable |
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.
Study Type : | Interventional (Clinical Trial) |
Enrollment : | 115 participants |
Allocation: | Non-Randomized |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | Prospective Trial to Evaluate How Therapeutic Drug Monitoring of Protease Inhibitors Increases Virologic Success and Tolerance of HAART (ANRS 111 COPHAR2) |
Study Start Date : | July 2002 |
Study Completion Date : | March 2005 |
- treatment failure defined as viral load greater than 200 copies/ml between week 16 (W16) and week 48 (W48) (confirmed by 2 samples spiked at least 15 days apart but no more than 45 days after virological failure, assayed by 50 copies/ml method)
- toxicity related to PI, defined as adverse event grade 3 or 4 with ANRS quotation, renal colic, diarrhoea grade 2, or cholesterolemia over 10 times the normal value
- virological failure: viral load over 200 copies/ml between W16 and W48 (confirmed by 2 samples spiked at least 15 days apart but no more than 45 days after virological failure, assayed by 50 copies/ml method)
- toxicity related to PI: adverse events grade 3 or 4 with ANRS quotation, renal colic, diarrhoea grade 2, or cholesterolemia over 10 times the normal value
- patients with trough plasma concentrations outside the therapeutic range at W24 and W48
- concentration changes with dosage variation
- time to obtain a viral load below 200 copies/ml
- relationship between adverse events grade 3 or 4 related to PI and plasma concentration at week 2 (W2)
- relationship between pharmacokinetic parameters and/or plasma concentrations and the drop of viral load between day 0 (D0) and W2 and between D0 and week 4 (W4)
- relationship between pharmacokinetic parameters and viral mutations occurring during the treatment of patients with virological failure (over 1000 copies/ml after week 24 [W24])
- PI pharmacokinetic parameter estimation and evaluation of variability
- pharmacokinetic variability of nucleoside analogues at W2
- intracellular concentration of nucleoside triphosphate derivatives at W2 (trough and maximum) and relationship between virological response and adverse events
- relationship between inhibitory quotient of indinavir and virological response

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00122590
France | |
Service de Medecine Interne Hopital Cochin | |
Paris, France, 75014 |
Principal Investigator: | Dominique Salmon, MD | Service de Medecine Interne Hopital Cochin Paris | |
Study Chair: | France Mentre, MD | Inserm EMI 03 57 |
ClinicalTrials.gov Identifier: | NCT00122590 |
Other Study ID Numbers: |
ANRS111 COPHAR 2 |
First Posted: | July 22, 2005 Key Record Dates |
Last Update Posted: | August 1, 2005 |
Last Verified: | July 2005 |
protease inhibitors nelfinavir lopinavir indinavir Pharmacokinetics |
HIV Infections Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immunologic Deficiency Syndromes Immune System Diseases Ritonavir Lopinavir Nelfinavir |
Indinavir HIV Protease Inhibitors Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-HIV Agents Anti-Retroviral Agents Antiviral Agents Anti-Infective Agents Cytochrome P-450 CYP3A Inhibitors Cytochrome P-450 Enzyme Inhibitors |