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

French National Agency for Research on AIDS and Viral Hepatitis

Status and phase: Terminated; Phase 2

Conditions: HIV Infections

Treatments: Drug: Ritonavir; Drug: Indinavir; Drug: Lamivudine

Study type: Interventional

Funder types: Other

Identifiers

NCT00120783

ANRS 109 VISTA

Details and patient eligibility

About

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

Full 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

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)