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

Purpose

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

Condition	Intervention	Phase
HIV Infections	Drug: Indinavir Drug: Lamivudine Drug: Ritonavir	Phase 2


Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment
Official Title:	Efficacy and Tolerability of an Antiretroviral bi-Therapy in HIV-1 Infected Patients With Multidrug Resistant HIV ANRS 109 Vista Trial.

Resource links provided by NLM:

MedlinePlus related topics: HIV/AIDS

U.S. FDA Resources

Further study details as provided by French National Agency for Research on AIDS and Viral Hepatitis:

Primary Outcome Measures:

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 Outcome Measures:

Development of an HIV-1-related AIDS defining event
Death
Change in CD4 cell count between baseline and week 24
Change in plasma HIV-RNA level between baseline and week 4, week 8, week 12 and week 24
Change in genotypic and phenotypic resistance between baseline and week 2


Estimated Enrollment:	40
Study Start Date:	February 2002
Estimated Study Completion Date:	August 2003

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


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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

Contacts and Locations

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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00120783

Locations


France
Service de Medecine Interne hopital Avicenne
Bobigny, France, 93009 cedex

Sponsors and Collaborators

French National Agency for Research on AIDS and Viral Hepatitis

Investigators


Principal Investigator:	Odile Launay, MD	Hopital Avicenne,Bobigny, Service de Médecine Interne
Study Chair:	Dominique Costagliola	Inserm U720

More Information


ClinicalTrials.gov Identifier:	NCT00120783 History of Changes
Other Study ID Numbers:	ANRS 109 VISTA
Study First Received:	July 12, 2005
Last Updated:	January 17, 2007

Keywords provided by French National Agency for Research on AIDS and Viral Hepatitis:


Treatment Failure HIV infections

Additional relevant MeSH terms:


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 Indinavir Lamivudine	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 Reverse Transcriptase Inhibitors Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on August 18, 2017