Peripheral Body Fat Distribution After Switching Zidovudine and Lamivudine to Truvada

NCT ID: NCT00324649

Last Updated: 2015-08-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-05-31
• Study Completion Date: 2008-09-30

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).

Conditions

HIV-1

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Truvada

Truvada + NNRTI or PI.

Group Type: EXPERIMENTAL

Truvada

Intervention Type: DRUG

Truvada once daily with continuation of the current NNRTI or PI at randomization.

Zidovudine/lamivudine

Zidovudine/lamivudine + NNRTI or PI.

Group Type: ACTIVE_COMPARATOR

Zidovudine/lamivudine

Intervention Type: DRUG

Continuation of the zidovudine + lamivudine containing regimen plus the current NNRTI or PI at randomization.

Interventions

Truvada

Truvada once daily with continuation of the current NNRTI or PI at randomization.

Intervention Type: DRUG

Zidovudine/lamivudine

Continuation of the zidovudine + lamivudine containing regimen plus the current NNRTI or PI at randomization.

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gilead Sciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Pedro Ferrer

Role: STUDY_DIRECTOR

Gilead Sciences, S.L.

Locations

Gilead Sciences, S.L.

Madrid, , Spain

Countries

Spain

Other Identifiers

GS-ES-164-0154

Identifier Type: -

Identifier Source: org_study_id