GMB: Study of Truvada (TDF+FTC) or Emtricitabine (FTC) Alone Versus HAART Interruption in HIV-Infected Patients With Resistance
Information provided by (Responsible Party)
First received: August 9, 2006
Last updated: March 30, 2009
Last Verified: March 2009
History of Changes
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.
Drug : Truvada (TDF+FTC) alone
Drug : FTC alone
Procedure : No HAART
Intervention Model: Parallel Assignment
Masking: None (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|
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 ]
- Proportion of patients with re-initiation of HAART within 24 and 48 weeks [ Time Frame: Through 48 weeks ]
- To compare CD4 cell loses 48 weeks after HAART discontinuation [ Time Frame: Through 48 weeks ]
- 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 ]
- 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 ]
- 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 ]
- 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 ]
- To compare development of new mutations in the reverse transcriptase gene 24 and 48 weeks after HAART discontinuation. [ Time Frame: Through 48 weeks ]
- Proportion of patients with any adverse event. [ Time Frame: Through 48 weeks ]
- Proportion of patients for each adverse event. [ Time Frame: Through 48 weeks ]
- 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 ]
- 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 ]
- Proportion of patients who discontinue the study prematurely (before week 48)due to adverse events. [ Time Frame: Through 48 weeks ]
- Changes in patient's quality of life analyses. [ Time Frame: Through 48 weeks ]
|Study Start Date:||November 2006|
|Study Completion Date:||October 2008|
|Primary Completion Date:||May 2008 (Final data collection date for primary outcome measure)|
Truvada 1 tablet once a day.
Truvada (TDF+FTC) alone
tenofovir DF 300 mg and emtricitabine 200 mg in a fixed dose tablet formulation
Procedure: No HAART
Emtricitabine 1 capsule once a day
emtricitabine 200 mg
Procedure: No HAART
Virological failure associated with the appearance of resistant mutations is still common in patients receiving HAART. When HAART fails patients and clinicians can chose from three different courses of action:
- Switch therapy to a new salvage regimen based on the results of resistance testing.
Success of the new salvage regimen is maximized if the new regimen includes antiretroviral drugs without cross-resistance with previous failed drugs or, preferably,new classes of drugs. In general, rescue regimens are more complicated for patients due to its higher pill burden; more frequent dosing and sometimes need for parenteral therapy (Enfuvirtide).
Choosing among these three different strategies depends on a number of important factors.
Apart from the setting of virological failure HAART interruption might be needed in patients with well controlled viral replication (HIV viremia persistently below 50 copies/ mL). Possible reasons for HAART interruption in this scenario are:
|Ages Eligible for Study:||18 Years and older|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
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:
- 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).
- 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.
- 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
Patients receiving a non-registered antiretroviral (ARV) drug.
Contacts and LocationsChoosing 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: NCT00362687
Locations Show More
|Gilead Sciences, S.L.|
|Madrid, Spain, E-28036|
Sponsors and CollaboratorsGilead Sciences
|Study Director:||Pedro Ferrer||Gilead Sciences, S.L.|
|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|
Keywords provided by Gilead Sciences:HIV, HAART
Additional relevant MeSH terms:
Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
ClinicalTrials.gov processed this data on October 20, 2017
This information is provided by ClinicalTrials.gov.