Clinical trial NCT00324649: Peripheral Body Fat Distribution After Switching Zidovudine and Lamivudine to Truvada
Official title: Pilot Phase IV, Multicenter, Randomized, Open-label and Controlled Study to Assess the Evolution of Peripheral Body Fat Distribution After Switching From Zidovudine Containing Backbone to Truvada in HIV-1-infected Patients on HAART (RECOMB Study).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: HIV-1
Keywords: HIV-1
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2006-05-11
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study evaluated changes in body fat distribution in human immunodeficiency virus type 1 (HIV-1) infected participants who either switched from a zidovudine- plus lamivudine- containing highly active antiretroviral therapy (HAART) regimen to a regimen containing Truvada® (a fixed-dose combination tablet of emtricitabine \[FTC, 200 mg\] and tenofovir disoproxil fumarate \[TDF, 300 mg\]) or who remained on a zidovudine- plus lamivudine-containing regimen. Subjects continued their protease inhibitor (PI) or nonnucleoside reverse transcriptase inhibitor (NNRTI).

Detailed description: Standard care for the treatment of HIV infection involves the use of a combination of three antiretroviral drugs. The initial recommended regimen in antiretroviral-naive patients according to therapeutic guidelines of the US Department of Health and Human Resources (DHHS) includes two nucleoside reverse transcriptase inhibitors (NRTIs) and a third drug from another class (PI or NRTI).

The use of nucleoside analogues, especially stavudine and zidovudine, is associated with untoward side effects, including lipodystrophy hepatic steatosis/lactic acidosis syndrome, peripheral neuropathy, and anemia. However, Truvada has a low potential for both mitochondrial toxicity and fat distribution disturbances.

As described in the Consensus Document of the Spanish Group for the Study of AIDS (GESIDA), and the AIDS National Plan from the Spanish Ministry of Health "Recommendations on metabolic alterations and body fat distribution", studies should focus on the evaluation of body fat disturbances after antiretroviral drug substitutions, based on the basic assumption of virologic control of the patient and equivalence in potency of the new drug regarding virological control. In addition, studies based on selective substitution of antiretroviral drugs in HIV-1 infected patients under virological control, are recommended in the European Medicines Agency (EMA) in the "Guideline on the clinical development of medicinal products for the treatment of HIV infection".

In this study, stable, virologically controlled, HIV-1 infected participants receiving antiretroviral regimens containing zidovudine and lamivudine were randomized to switch to Truvada or to stay on their zidovudine- plus lamivudine-containing regimen. Participants in both groups continued the third drug of their antiretroviral regimen (either an NNRTI or PI). Changes in limb fat in the two groups were assessed using dual-energy x-ray absorptiometry (DEXA).

Eligibility criteria: Inclusion Criteria:

* HIV-1 infection documented by confirmed positive HIV-1 antibody test and/or positive polymerase chain reaction for HIV-1 ribonucleic acid (RNA).
* Adult patients (over 18 years of age).
* Current HAART regimen containing zidovudine + lamivudine at usual doses for at least 6 months.
* Viral load \< 50 copies/mL on the last two consecutive determinations, under zidovudine + lamivudine containing HAART regimen.
* 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 on lipid lowering treatment were allowed to participate in the study only if the lipid-lowering treatment (either statins or fibrates) was stable for at least 8 weeks prior to screening and it was not expected to change during the first 3 months of the study.

Exclusion Criteria:

* Patients on current FTC or TDF therapy.
* Patients with previous history of virological failure on an FTC or TDF-containing regimen.
* Patients receiving a non-registered antiretroviral drug.
* Patients receiving a triple-nucleoside antiretroviral combination.
* Hypersensitivity to one of the components of the dosage forms of TDF or FTC, or previous history of intolerance to one of those drugs.
* Known history of drug abuse or chronic alcohol consumption
* Women who were pregnant or breast feeding, or female of childbearing potential who did not use an adequate method of contraception according to the investigator's judgment.
* 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 which could not be stopped without affecting the safety of the patient.
* Receiving on-going therapy with systemic corticosteroids, Interleukin-2 or chemotherapy.
* Patients who were not to be included in the study according to the investigator's criterion.

Primary outcomes:
measure: Change From Baseline in Limb Fat at Week 48
timeFrame: Baseline to Week 48
Secondary outcomes:
measure: Change From Baseline in the Mitochondrial DNA/Nuclear DNA Ratio (Oral Mucosa)
timeFrame: Baseline to Week 48
measure: Change From Baseline in the Mitochondrial DNA/Nuclear DNA Ratio (Lymphocytes)
timeFrame: Baseline to Week 48
measure: Change From Baseline in Lactate Concentration
timeFrame: Baseline to Week 48
measure: Percentage of Days for Which Participants Were Compliant With Study Drug
timeFrame: Baseline to Week 72
measure: Percentage of Participants Who Maintain Confirmed HIV-1 RNA < 50 Copies/mL
timeFrame: 48 weeks
measure: Percentage of Participants With HIV-1 RNA > 50 and < 400 Copies/mL
timeFrame: 48 weeks
measure: Percentage of Participants With Virologic Failure
timeFrame: 48 weeks
measure: Change From Baseline in Cluster Determinant 4 (CD4) Cell Count
timeFrame: Baseline to Week 48
measure: Change From Baseline in Fasting Serum Triglycerides
timeFrame: Baseline to Week 48
measure: Change From Baseline in Fasting Total Cholesterol
timeFrame: Baseline to Week 48
measure: Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL)
timeFrame: Baseline to Week 48
measure: Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL)
timeFrame: Baseline to Week 48
measure: Change From Baseline in Hemoglobin
timeFrame: Baseline to Week 48
measure: Percent Change From Baseline in Hematocrit
timeFrame: Baseline to Week 48
measure: Change From Baseline in Waist Circumference/Hip Circumference Ratio
timeFrame: Baseline to Week 48
measure: Percentage of Participants With Any Adverse Event
timeFrame: 72 weeks
measure: Percentage of Participants Who Discontinue the Study Prematurely (Before Week 48) Due to Adverse Events.
timeFrame: 48 weeks
Other outcomes:
Locations:
city: Madrid
country: Spain
facility: Gilead Sciences, S.L.
Study officials:
affiliation: Gilead Sciences, S.L.
name: Pedro Ferrer
role: STUDY_DIRECTOR
References: