PREventing Progression of Adipose Tissue Redistribution

This study has been completed.
Sponsor:
Collaborator:
Gilead Sciences
Information provided by:
International Antiviral Therapy Evaluation Center
ClinicalTrials.gov Identifier:
NCT00389194
First received: October 17, 2006
Last updated: June 10, 2010
Last verified: June 2010
  Purpose

The main objective of the study is to assess changes in fat distribution over 48 weeks of treatment in patients who currently successfully use zidovudine (AZT) and lamivudine (3TC) as part of their regimen and who will either continue these antiretrovirals or who will switch these antiretrovirals to tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC). Each of these medications is commonly used for the treatment of HIV-1 infection.


Condition Intervention Phase
HIV Infections
Drug: continuing AZT+3TC or switching AZT+3TC to TDF+ FTC
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: A Randomized, Controlled, Open-Label, 48-Week Study of Continuing Successfully Suppressive Treatment in HIV-1 Infected Adults With First-Line Twice-Daily Zidovudine and Lamivudine-Based Regimens Versus Pro-actively Replacing of Zidovudine and Lamivudine by Once-Daily Emtricitabine and Tenofovir Disoproxil Fumarate to Prevent Progression of or Reverse Peripheral Lipoatrophy.

Resource links provided by NLM:


Further study details as provided by International Antiviral Therapy Evaluation Center:

Secondary Outcome Measures:
  • Difference between the continuation arm and the switch arm in:
  • changes in subcutaneous and visceral abdominal fat by CT and truncal fat by whole body DEXA over 48 weeks
  • changes in lipids (total-, HDL-, and LDL-cholesterol, total /HDL cholesterol ratio, triglycerides), and glucose-metabolism (glucose, insulin) and insulin resistance (HOMA-index1) over 48 weeks.
  • incidence of new onset of lipodystrophy and changes in lipodystrophy severity according to the LDCD score.
  • changes in bone mineral density by regional DEXA (vertebra L4 and femoral neck) over 48 weeks
  • proportion of patients with plasma HIV-1 RNA concentrations < 50 copies/mL after 48 weeks and proportion of patients that developed new CDC-C events or increased in CDC classification.
  • incidence and severity of adverse events (grade 3 and 4), and laboratory abnormalities (grade 1-4)
  • A comparison between different GFR-estimations and the gold standard for GFR-measurement in HIV-1 infected patients on HAART. [ Time Frame: baseline ] [ Designated as safety issue: No ]
    Conclusions: Each eGFR estimation underestimated the mGFR. In patients with preserved renal function and suppressed HIV-infection, C&G, 24-hours urine clearance and MDRD-6 based eGFR reasonably estimated true GFR, but cysC-based eGFR did not.


Estimated Enrollment: 120
Study Start Date: April 2006
Study Completion Date: October 2008
  Show Detailed Description

  Eligibility

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

Inclusion Criteria:

  • Providing written informed consent
  • HIV-1 infected patients.
  • At least 18 years of age.
  • Males or non-pregnant, non-lactating females. Women of childbearing age must have a negative urine pregnancy test at screening. All female participants must be encouraged to utilise adequate contraception for the month preceding entry and for the duration of the study.
  • Treatment for at least two years with a first-line regimen of zidovudine plus lamivudine (as either a fixed dose combination or dosed separately) plus either an NNRTI or a (boosted) PI. Patients may have previously used multiple drugs from both the NNRTI or the PI classes.
  • Plasma HIV-1 RNA levels < 50 copies/mL for at least 6 months at screening. Isolated measurements of plasma HIV-1 RNA levels above 50 but below 200 copies/ml (socalled blips) are allowed.

Exclusion Criteria:

  • Prior treatment with an NRTI other than zidovudine or lamivudine.
  • Use of a triple NRTI antiretroviral regimen or a regimen including unboosted saquinavir, fusion inhibitors or hydroxyurea
  • Prior virological treatment failure, defined as having had to switch antiretroviral therapy because of virologic failure in the opinion of the physician.
  • HIV-2 co-infection.
  • Renal impairment and/or use of nephrotoxic agents which in the opinion of the investigator are a contraindication for the use of tenofovir disoproxil fumarate.
  • Clinically relevant laboratory abnormalities: anemia, thrombocytopenia, leucopenia, elevated liver transaminases, elevated bilirubin, elevated amylase, elevated lipase.
  • Use of co-medication, other than antiretroviral drugs, with a known pharmacological interaction with one or more of the study drugs
  • Active alcohol or drug use, sufficient in the investigator's opinion to prevent compliance with the dosing schedule and evaluations (methadone and buprenorphine use is allowed, although the dose of methadone might need to be adjusted).
  • Anticipated non-compliance with the protocol.
  • Presence of a newly (within 30 days prior to the time of enrolment) diagnosed HIV-related opportunistic infection or condition which may interfere with the ability to comply with the study.
  • Chronic active viral hepatitis or other chronic liver disease, which in the opinion of the investigator is a contraindication for the use of any of the study drugs.
  • Women who have the intention to become pregnant during the study period.
  • Patients who have received within 4 weeks prior to entry, or who have an anticipated need for treatment with radiation therapy or cytotoxic chemotherapeutic agents during the protocol study period.
  • Patients who have taken any investigational drug 30 days prior to the start of the study
  • Patients with malabsorption syndrome or other gastrointestinal dysfunction which may interfere with drug absorption or prevent the patient from taking oral medication.
  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: NCT00389194

Locations
Netherlands
Academic Medical Centre
Amsterdam, Netherlands
Sponsors and Collaborators
International Antiviral Therapy Evaluation Center
Gilead Sciences
Investigators
Study Chair: Peter Reiss, MD, PhD Academic Medical Centre
  More Information

No publications provided by International Antiviral Therapy Evaluation Center

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00389194     History of Changes
Other Study ID Numbers: PR-0095_01, Eudract number: 2005-005672-33
Study First Received: October 17, 2006
Last Updated: June 10, 2010
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by International Antiviral Therapy Evaluation Center:
HIV-1 infection
fat distribution
lipodystrophy
lipids
kidney function
Treatment Experienced

Additional relevant MeSH terms:
Infection
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
Lamivudine, zidovudine drug combination
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on September 16, 2014