Immuno-Virological Efficacy of Combination With Trizivir +Tenofovir in Multiresistant HIV Patients - Full Text View

Sponsors and Collaborators:	Germans Trias i Pujol Hospital FUNDACIÓ LLUITA CONTRA LA SIDA
Information provided by:	Germans Trias i Pujol Hospital
ClinicalTrials.gov Identifier:	NCT00356616

Purpose

To evaluate whether the combined therapy of two nucleosides plus one nucleotide (Trizivir + TDF) manages to keep CD4 lymphocytes stable in patients with HIV infection on antiretroviral treatment that present virological failure and multiple resistance to antiretrovirals.

Condition	Intervention	Phase
HIV Infections	Drug: Trizivir (AZT+3HT+Abacavir) twice daily Drug: Viread (300 mg Tenofovir disoproxil fumarate) once daily	Phase IV

MedlinePlus related topics: AIDS

Drug Information available for: Abacavir Abacavir sulfate Tenofovir Tenofovir disoproxil Tenofovir Disoproxil Fumarate Trizivir

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	Open-Label, Single-Centre, Randomised Pilot Study to Evaluate Immunovirological and Clinical Evolution of a Combination With Nucleoside Analogues/Nucleotides (Trizivir +Tenofovir) in Multiresistant Patients With Virological Failure

Further study details as provided by Germans Trias i Pujol Hospital:

Primary Outcome Measures:

Variations in the immune status of patients in each group throughout follow-up. [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Percentage of patients that increase viral load by > 0.5 log [ Time Frame: weeks 12, 24, 36 and 48 ] [ Designated as safety issue: No ]
Percentage of patients that increase viral load by > 100,000 copies/mL [ Time Frame: weeks 12, 24, 36 and 48 ] [ Designated as safety issue: No ]
Percentage of patients that present some clinical event, B or C classification according to the CDC. [ Time Frame: during the 48 weeks of follow-up ] [ Designated as safety issue: Yes ]
Percentage of patients that present clinical or analytical adverse effects degree > 2 according to the WHO classification. [ Time Frame: weeks 12, 24, 36 and 48 ] [ Designated as safety issue: Yes ]
Percentage of patients that drop out of treatment. [ Time Frame: weeks 12, 24, 36 and 48 ] [ Designated as safety issue: Yes ]
Percentage of patients that drop out of the study due to intolerance or adverse effects. [ Time Frame: weeks 12, 24, 36 and 48 ] [ Designated as safety issue: Yes ]
Percentage of change in lipid determinations. [ Time Frame: weeks 12, 24, 36 and 48 with regard to baseline ] [ Designated as safety issue: Yes ]
Percentage of patients that report changes, improvement or worsening in redistribution of body fat. [ Time Frame: weeks 12, 24, 36 and 48 ] [ Designated as safety issue: No ]
Percentage of patients that present adherence to the antiretroviral treatment > 95%. [ Time Frame: weeks 12, 24, 36 and 48 ] [ Designated as safety issue: No ]
Percentage of patients that present improvement in the quality of life (MOS-HIV) and satisfaction questionnaires. [ Time Frame: weeks 12, 24, 36 and 48 ] [ Designated as safety issue: No ]
Percentage of patients that present an increase in the number of active drugs. [ Time Frame: at the end of the study ] [ Designated as safety issue: No ]

Enrollment:	24
Study Start Date:	September 2005
Study Completion Date:	June 2007
Primary Completion Date:	June 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
A: Experimental Trizivir+ Tenofovir 2/day	Drug: Trizivir (AZT+3HT+Abacavir) twice daily Trizivir (AZT+3HT+Abacavir) twice daily Drug: Viread (300 mg Tenofovir disoproxil fumarate) once daily Viread (300 mg Tenofovir disoproxil fumarate) once daily
B: No Intervention antiretroviral treatment optimizated by genotyp

Detailed Description:

This study has been designed to determine whether the use of a regimen based exclusively on NTRI, containing tenofovir, zidovudine and lamivudine, is able to preserve immunological status in patients with detectable viral load for whom an efficacious salvage regimen cannot be designed, slowing the progression of the viral load and reducing antiretroviral treatment-associated toxicity. In order to complete the salvage regimen without increasing the number of tablets too much, Trizivir plus tenofovir as investigational treatment will be used.

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Age>= 18 years.
HIV-1 infected patients.
Patients on antiretroviral treatment including NTRI + PI +/- NNRTI +/- fusion inhibitors at inclusion in the study.
Virological failure, defined as 2 determinations with viral load >1,000 copies/mL in the last 6 months, during stable HAART therapy over the previous 6 months.
Genotype or phenotype resistance to three families of antiretrovirals (PI, NTRI and NNRTI) demonstrated in genotype study carried out in the last 48 weeks and defined as:
- 3 or more TAMS of the following: M41L, E44D, D67N, V118I, L210W, T215Y/F, K219Q/E.
- Existence of the M184V mutation or probable presence in the cellular archives.
- 5 or more mutations that confer resistance to PI of the following: I10F/I/R/V, V32I, M46I/L, I54V/M/L, V82A/F/T/S/V, I84V/A/C, L90M.
- Existence of 1 or more mutations that confer resistance to NNRTI, or probable presence in the cellular archives of: K103N, Y181C/I/Y, G190S/A/G.
CD4 lymphocytes >- 300 cells/mm3 in the last two determinations.
Subject able to follow the treatment period.
Acceptance of the study and signature of the informed consent form.
Women may not be of fertile age (defined as at least one year from menopause or undergoing any surgical sterilisation technique), or must undertake to use a barrier contraceptive method during the study.

Exclusion Criteria:

Suspicion of previous incorrect adherence.
Pregnancy or breastfeeding
Suspicion of intolerance to any investigational drug.
Record of any disease which, according to clinical criteria, may reoccur with the proposed change of therapy (sarcoma, lymphoma, etc).
CD4 Nadir below 200 cel/mm3.
Acute intercurrent disease or fever in the 15 days before inclusion.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00356616

Locations

Spain, Barcelona
H.U. Germans Trias i Pujol
Badalona, Barcelona, Spain, 08916

Sponsors and Collaborators

Germans Trias i Pujol Hospital

FUNDACIÓ LLUITA CONTRA LA SIDA

Investigators

Principal Investigator:

Bonaventura Clotet, MD,PhD

LLuita contra la Sida Foundation-HIV Unit

More Information

Responsible Party:	Lluita Sida Foundation ( Lluita Sida Foundation )
Study ID Numbers:	TETRIZ, 2005-002203-17
Study First Received:	July 24, 2006
Last Updated:	January 25, 2008
ClinicalTrials.gov Identifier:	NCT00356616
Health Authority:	Spain: Ministry of Health

Keywords provided by Germans Trias i Pujol Hospital:

Antiretroviral treatment
virological failure
HIV

Study placed in the following topic categories:

Virus Diseases
Sexually Transmitted Diseases, Viral
HIV Infections
Sexually Transmitted Diseases
Acquired Immunodeficiency Syndrome

Tenofovir
Abacavir
Retroviridae Infections
Immunologic Deficiency Syndromes
Tenofovir disoproxil

Additional relevant MeSH terms:

Anti-Infective Agents
RNA Virus Infections
Anti-HIV Agents
Slow Virus Diseases
Immune System Diseases
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Infection

Antiviral Agents
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Anti-Retroviral Agents
Therapeutic Uses
Lentivirus Infections
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on January 16, 2009