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

Phase 4

Terminated

• Conditions: HIV Infections
• Interventions: Drug: Trizivir (AZT+3HT+Abacavir) twice daily; Drug: Viread (300 mg Tenofovir disoproxil fumarate) once daily

• Registration Number: NCT00356616
• Lead Sponsor: Germans Trias i Pujol Hospital

Brief Summary

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.

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.

Study Timeline

• Study Start: 2005-09
• Study First Submitted: 2006-07-24
• Study First Submitted QC: 2006-07-25
• Study First Posted: 2006-07-26
• Primary Completion: 2007-06
• Study Completion: 2007-06
• Status Verified: 2007-11
• Last Update Submitted: 2008-01-25
• Last Update Posted: 2008-01-29

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

1. Age>= 18 years.

2. HIV-1 infected patients.

3. Patients on antiretroviral treatment including NTRI + PI +/- NNRTI +/- fusion inhibitors at inclusion in the study.

4. 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.

5. 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.

6. CD4 lymphocytes >- 300 cells/mm3 in the last two determinations.

7. Subject able to follow the treatment period.

8. Acceptance of the study and signature of the informed consent form.

9. 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
A	Trizivir (AZT+3HT+Abacavir) twice daily	Trizivir+ Tenofovir 2/day
A	Viread (300 mg Tenofovir disoproxil fumarate) once daily	Trizivir+ Tenofovir 2/day

Primary Outcome Measures

Name	Time	Method
Variations in the immune status of patients in each group throughout follow-up.	48 weeks

Secondary Outcome Measures

Name	Time	Method
Percentage of patients that present some clinical event, B or C classification according to the CDC.	during the 48 weeks of follow-up
Percentage of patients that drop out of treatment.	weeks 12, 24, 36 and 48
Percentage of patients that increase viral load by > 100,000 copies/mL	weeks 12, 24, 36 and 48
Percentage of patients that present clinical or analytical adverse effects degree > 2 according to the WHO classification.	weeks 12, 24, 36 and 48
Percentage of patients that increase viral load by > 0.5 log	weeks 12, 24, 36 and 48
Percentage of patients that drop out of the study due to intolerance or adverse effects.	weeks 12, 24, 36 and 48
Percentage of change in lipid determinations.	weeks 12, 24, 36 and 48 with regard to baseline
Percentage of patients that report changes, improvement or worsening in redistribution of body fat.	weeks 12, 24, 36 and 48
Percentage of patients that present adherence to the antiretroviral treatment > 95%.	weeks 12, 24, 36 and 48
Percentage of patients that present improvement in the quality of life (MOS-HIV) and satisfaction questionnaires.	weeks 12, 24, 36 and 48
Percentage of patients that present an increase in the number of active drugs.	at the end of the study

Trial Locations

Locations (1)

H.U. Germans Trias i Pujol; 🇪🇸 Badalona, Barcelona, Spain