GMB: Study of Truvada (TDF+FTC) or Emtricitabine (FTC) Alone Versus HAART Interruption in HIV-Infected Patients With Resistance - Full Text View

Purpose

Many patients who already harbor drug-resistant HIV require interruption of HAART due to poor compliance, poor quality of life, toxicity or development of resistance. In these patients interruption of HAART has a negative impact on patient immune status due to the reemergence of wild-type virus which is in general more pathogenic than HIV isolates containing resistance mutations. There is a need for "bridging" antiretroviral regimens that might prolong time off conventional HAART whilst waiting for a new regimen that is either fully suppressive or less toxic or less demanding for the patient.

Condition	Intervention	Phase
HIV Infections	Drug: Truvada (TDF+FTC) alone Drug: FTC alone Procedure: No HAART	Phase 4

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	GMB: Phase IV, Multicenter, Randomized, Open-Label Pilot Study of Truvada (TDF+FTC) or Emtricitabine (FTC) Alone Versus HAART Interruption in HIV-Infected Patients Who Need to Interrupt HAART and Who Are Infected With HIV Isolates Containing at Least 2 TAMs (or K65R) and M184V

Resource links provided by NLM:

Genetics Home Reference related topics: complement factor I deficiency

MedlinePlus related topics: HIV/AIDS

Drug Information available for: Emtricitabine Truvada

U.S. FDA Resources

Further study details as provided by Gilead Sciences:

Primary Outcome Measures:

To compare CD4 cell loses 24 weeks after HAART discontinuation [ Time Frame: Through 48 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Proportion of patients with re-initiation of HAART within 24 and 48 weeks [ Time Frame: Through 48 weeks ] [ Designated as safety issue: No ]
To compare CD4 cell loses 48 weeks after HAART discontinuation [ Time Frame: Through 48 weeks ] [ Designated as safety issue: No ]
To compare HIV viral loads 4, 24 and 48 weeks after HAART discontinuation:time-weighted average change from baseline through 24 and 48 weeks (DAVG24 and DAVG48) for log10 plasma HIV-1 RNA for patients with plasma HIV-1 RNA >50 copies/mL at baseline [ Time Frame: Through 48 weeks ] [ Designated as safety issue: No ]
To compare HIV viral loads 4, 24 and 48 weeks after HAART discontinuation: time-weighted average change from 4 weeks through 24 and 48 weeks (DAVG24 and DAVG48) for log10 plasma HIV-1 RNA for patients with <50 copies/mL at baseline [ Time Frame: Through 48 weeks ] [ Designated as safety issue: No ]
To compare HIV viral loads 4, 24 and 48 weeks after HAART discontinuation: proportion of patients with HIV RNA <400 and <50 copies/mL at 4 weeks for subjects with plasma HIV-1 RNA <50 copies/mL at baseline [ Time Frame: Through 48 weeks ] [ Designated as safety issue: No ]
To compare HIV viral loads 4, 24 and 48 weeks after HAART discontinuation: compare log10 plasma HIV-1 RNA at week 4 for patients with HIV-RNA < 50 copies/mL at baseline. [ Time Frame: Through 48 weeks ] [ Designated as safety issue: No ]
To compare development of new mutations in the reverse transcriptase gene 24 and 48 weeks after HAART discontinuation. [ Time Frame: Through 48 weeks ] [ Designated as safety issue: No ]
Proportion of patients with any adverse event. [ Time Frame: Through 48 weeks ] [ Designated as safety issue: No ]
Proportion of patients for each adverse event. [ Time Frame: Through 48 weeks ] [ Designated as safety issue: No ]
Distribution of the intensity if each adverse event (the greatest intensity for each adverse event within a patient will be considered). [ Time Frame: Through 48 weeks ] [ Designated as safety issue: No ]
Distribution of the relationship between the adverse effect and the study drug (the strongest relation with the study drug for each adverse event within each patient will be considered). [ Time Frame: Through 48 weeks ] [ Designated as safety issue: No ]
Proportion of patients who discontinue the study prematurely (before week 48)due to adverse events. [ Time Frame: Through 48 weeks ] [ Designated as safety issue: No ]
Changes in patient's quality of life analyses. [ Time Frame: Through 48 weeks ] [ Designated as safety issue: No ]

Enrollment:	50
Study Start Date:	November 2006
Study Completion Date:	October 2008
Primary Completion Date:	May 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 Truvada 1 tablet once a day.	Drug: Truvada (TDF+FTC) alone tenofovir DF 300 mg and emtricitabine 200 mg in a fixed dose tablet formulation Procedure: No HAART No HAART
Experimental: 2 Emtricitabine 1 capsule once a day	Drug: FTC alone emtricitabine 200 mg Procedure: No HAART No HAART

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Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

HIV-1 infection documented by confirmed positive HIV-1 antibody test and/or positive PCR for HIV-1 RNA.

Adult patients (over 18 years of age).
Available genotype (current or historical) showing M184V and (≥ 2 TAMs or K65R).
CD4 cell count ≥ 350 cells/mL.
Patient request HAART interruption due to any of the following:
1. Patient is receiving a suppressive HAART regimen but has problems with adherence,quality of life or toxicity AND there is no alternative simpler, less toxic regimen (typically patients with substantial resistance and good virological control while receiving multiple antiretrovirals).
2. Due to resistance, patient is receiving a non-suppressive HAART regimen but patient is not willing to change to a new, already available, more complicated optimized salvage regimen (typically 3rd or 4th line of therapy).
For women of childbearing potential, negative urine pregnancy test at screening visit.
Agreement to take part in the study and sign the informed consent.

Exclusion Criteria:

Patients receiving a non-registered antiretroviral (ARV) drug.

Patients who have < 50 HIV-RNA copies/mL while receiving an NNRTI.
Serum HBsAg positive and patient is receiving an anti-HBV active nucleoside/nucleotide.
Hypersensitivity to one of the components of the dosage forms of TDF or FTC, or previous history of intolerance to one of these drugs.
Known history of drug abuse or chronic alcohol consumption that in the clinician opinion contraindicates participation in the study.
Women who are pregnant or breast feeding or females of childbearing potential who do not use an adequate method of contraception according to the investigator's judgment.
Current active opportunistic infection or documented infection within the previous 4 weeks.
Documented active malignant disease (excluding Kaposi sarcoma limited to the skin).
Renal disease with creatinine clearance < 50 mL/min.
Concomitant use of nephrotoxic or immuno-suppressive drugs (should be stopped prior to enrollment)
Receiving on-going therapy with systemic corticosteroids, Interleukin-2 (IL-2) or chemotherapy.
Patients who are not to be included in the study according to the investigator's criterion.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00362687

Locations

Spain
Gilead Sciences, S.L.
Madrid, Spain, E-28036

Sponsors and Collaborators

Gilead Sciences

Investigators

Study Director:

Pedro Ferrer

Gilead Sciences, S.L.

More Information

No publications provided

Responsible Party:	Pedro Ferrer, Gilead Sciences
ClinicalTrials.gov Identifier:	NCT00362687 History of Changes
Other Study ID Numbers:	GS-ES-164-0151
Study First Received:	August 9, 2006
Last Updated:	March 30, 2009
Health Authority:	Spain: Spanish Agency of Medicines

Keywords provided by Gilead Sciences:

HIV, HAART

Additional relevant MeSH terms:

HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases

Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Emtricitabine
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on June 18, 2013