Efficacy and Tolerability of an Antiretroviral Bi-Therapy in HIV Infected Patients With Multidrug Resistance

NCT ID: NCT00120783

Last Updated: 2007-01-18

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-02-28
• Study Completion Date: 2003-08-31

Brief Summary

This study investigated whether a calibrated reduction in antiretroviral drug pressures could stabilize the evolution and the pathogenic potential of resistant HIV viruses.

Detailed Description

In patients with HIV multidrug resistance, maintaining a failing full-dose HAART regimen usually results in significant drug toxicity and in continued accumulation of resistance mutations that can preclude future therapeutic options. In contrast, treatment interruption provokes the reemergence of wild-type virus with full replicative and pathogenic capacity. The researchers investigated whether a calibrated reduction in drug pressure could stabilize the evolution and the pathogenic potential of resistant virus.

A prospective pilot study was conducted in patients receiving protease inhibitor-based HAART with a resistance genotype predicting less than two active drugs according to the 2002 ANRS algorithm, CD4 counts over or equal to 100/mm3 and plasma HIV RNA below or equal to 5 log/ml. The treatment was low-dose IDV/RTV (200/100 BID) and 3TC 150mg BID. IDV doses were adjusted at week 4 to ensure a Cmin of 250+/-100ng/ml, which, based on a panel of multi-PI resistant viruses, was calculated to yield an inhibitory quotient (Cmin/IC50) of 0.50. Primary end-points were over 25% decrease in CD4 counts (immunological failure-IF), or over 0.7 log increase in plasma HIV RNA (virological failure-VF) at two consecutive monthly visits during the 24-week study. Inclusions were to stop when the total number of failures (VF+IF) reached 7

Conditions

HIV Infections

Study Design

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

Interventions

Indinavir

Intervention Type: DRUG

Lamivudine

Intervention Type: DRUG

Ritonavir

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• HIV-1 infection confirmed by Western Blot
• Karnofsky score over or equal to 70
• CD4 over or equal to 200/mm3
• Plasma viral RNA over or equal to 10 000 copies/ml and below 100 000 copies/ml.
• Stability of plasma viral load and CD4-during the last 3 months
• failure of two antiretroviral regimens with 2 PI and one NNRTI
• New efficacy drug on genotype not available
• Treatment on hand with 3 antiretroviral drugs with one PI since 3 months.
• Written inform consent
• Pregnancy

Exclusion Criteria

• Hemoglobin below 8g/dL
• Neutrophils below 750/mm3
• ASAT, ALAT over 5N
• Hepatic insufficiency (prothrombin below 50%)
• Acute opportunistic infection
• Immunotherapy
• Treatment with active antiretroviral regimen
• Treatment with enzyme inductor

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

Sponsors

French National Agency for Research on AIDS and Viral Hepatitis

OTHER_GOV

Sponsor Role: lead

Principal Investigators

Odile Launay, MD

Role: PRINCIPAL_INVESTIGATOR

Hopital Avicenne,Bobigny, Service de Médecine Interne

Dominique Costagliola

Role: STUDY_CHAIR

Inserm U720

Locations

Service de Medecine Interne hopital Avicenne

Bobigny, , France

Countries

France

Other Identifiers

ANRS 109 VISTA

Identifier Type: -

Identifier Source: org_study_id