Clinical trial NCT00120783: Efficacy and Tolerability of an Antiretroviral Bi-Therapy in HIV Infected Patients With Multidrug Resistance
Official title: Efficacy and Tolerability of an Antiretroviral bi-Therapy in HIV-1 Infected Patients With Multidrug Resistant HIV ANRS 109 Vista Trial.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: HIV Infections
Keywords: Treatment Failure
HIV infections
Lead sponsor: French National Agency for Research on AIDS and Viral Hepatitis
Sponsor class: OTHER_GOV
First posted: 2005-07-19
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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

Primary outcomes:
measure: Decrease over 25% in CD4 counts (immunological failure-IF), or increase over 0.7 log in plasma HIV RNA (virological failure-VF) at two consecutive monthly visits during the 24-week study
Secondary outcomes:
measure: Development of an HIV-1-related AIDS defining event
measure: Death
measure: Change in CD4 cell count between baseline and week 24
measure: Change in plasma HIV-RNA level between baseline and week 4, week 8, week 12 and week 24
measure: Change in genotypic and phenotypic resistance between baseline and week 2
Other outcomes:
Locations:
city: Bobigny
country: France
facility: Service de Medecine Interne hopital Avicenne
Study officials:
affiliation: Hopital Avicenne,Bobigny, Service de Médecine Interne
name: Odile Launay, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Inserm U720
name: Dominique Costagliola
role: STUDY_CHAIR
References: