Study of Treatment of Antiretroviral-naive, HIV-1-Infected Patients Comparing Tenofovir Disoproxil Fumarate Administered in Combination With Lamivudine and Efavirenz vs. Stavudine, Lamivudine and Efavirenz.

A Phase 3, Randomized, Double-Blind, Multicenter Study of the Treatment of Antiretroviral-naive, HIV-1-Infected Patients Comparing Tenofovir Disoproxil Fumarate Administered in Combination With Lamivudine and Efavirenz vs. Stavudine, Lamivudine and Efavirenz.(Extension)

To compare tenofovir DF plus lamivudine plus efavirenz vs. stavudine plus lamivudine plus efavirenz in the treatment of HIV-1-infected patients who have never taken antiretroviral drugs and have a viral load of less than 400 copies/mL at week 48.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Viread (tenofovir disoproxil fumarate); Drug: Sustiva (Efavirenz); Drug: Epivir (Lamivudine); Drug: Zerit (Stavudine) Placebo

Detailed Description

To compare the two treatment groups with the goal of achieving HIV-1 RNA levels less than 50 copies/mL at week 48.

To compare the safety, efficacy and tolerability of the two treatment regimens through 144 weeks of drug exposure.

To evaluate the long-term efficacy, safety and tolerability of tenofovir DF in combination with lamivudine and efavirenz through approximately 336 weeks of drug exposure.

• Study Type: Interventional
• Enrollment (Anticipated): 180
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Completed the original 96-weeks of open-label treatment. Willingness to use effective contraception by both males and females while on study treatment and for 30 days following study drugs completion. The ability to understand and sign a written informed consent form, which must be obtained prior to initiation of any study procedures related to the second 96-week open-label phase extension.

Exclusion Criteria:

• Patients requiring therapy with any of the following: Nephrotoxic agents (aminoglycoside antibiotics, IV amphotericin B, cidofovir, cisplatin, foscarnet, IV pentamidine, oral and IV vancomycin, oral and IV ganciclovir, other agents with significant nephrotoxic potential);Probenecid; Systemic chemotherapeutic agents; Systemic corticosteroids; Interleukin-2 (IL-2); Investigational agents (except on approval by Gilead Sciences); Drugs that interact with efavirenz (astemizole, terfenadine, dihydroergotamine, ergotamine, midazolam, triazolam, cisapride, rifampin, ergonovine, methylergonovine, voriconazole). Administration of any of the listed medications is not allowed throughout the duration of the study period.
• Pregnant or lactating patients.
• Evidence of a gastrointestinal malabsorption syndrome or chronic nausea or vomiting which may confer an inability to receive an orally administered medication.
• Current alcohol or substance abuse judged by the investigator to potentially interfere with patient compliance.
• Malignancy other than cutaneous Kaposi's sarcoma (KS) or basal cell carcinoma. Patients with biopsy-confirmed cutaneous KS are eligible, if they are not anticipated to require systemic therapy during the study.
• Active, serious infections(other than HIV-1 infection) requiring parenteral antibiotic therapy.
• Any other clinical condition or prior therapy that, in the opinion of the investigator, would make the patient unsuitable for the study or unable to comply with the dosing requirements.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To compare the two treatment groups with the goal of achieving HIV-1 RNA levels less than 50 copies/mL at week 48.	compare the two treatment groups with the goal of achieving HIV-1 RNA levels	Week 48
To compare the safety, efficacy and tolerability of the two treatment regimens through 144 weeks of drug exposure.	compare the safety, efficacy and tolerability of the two treatment regimens through 144 weeks of drug exposure	144 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the long-term efficacy, safety and tolerability of tenofovir DF in combination with lamivudine and efavirenz through approximately 336 weeks of drug exposure.	evaluate the long-term efficacy, safety and tolerability of tenofovir DF in combination with lamivudine and efavirenz through approximately 336 weeks of drug exposure	336 Weeks
To evaluate the long term efficacy, safety and tolerability of tenofovir DF in combination with lamivudine and efavirenz through approximately 480 weeks of drug exposure.	evaluate the long term efficacy, safety and tolerability of tenofovir DF in combination with lamivudine and efavirenz through approximately 480 weeks of drug exposure.	480 Weeks
To evaluate the long term efficacy, safety and tolerability of tenofovir DF through approximately 624 weeks of drug exposure.	evaluate the long term efficacy, safety and tolerability of tenofovir DF through approximately 624 weeks of drug exposure	624 Weeks

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Investigators: Study Director: Erin Quirk, M.D., Gilead Sciences

Publications and helpful links

General Publications

• Madruga JR, Cassetti I, Suleiman JM, Etzel A, Zhong L, Holmes CB, Cheng AK, Enejosa J; Study 903E Team. The safety and efficacy of switching stavudine to tenofovir df in combination with lamivudine and efavirenz in hiv-1-infected patients: three-year follow-up after switching therapy. HIV Clin Trials. 2007 Nov-Dec;8(6):381-90. doi: 10.1310/hct0806-381.

Helpful Links

• Gilead Website

Study record dates

Study Major Dates

• Study Start: March 1, 2000
• Primary Completion (Actual): December 1, 2001
• Study Completion (Actual): June 1, 2013

Study Registration Dates

• First Submitted: September 7, 2005
• First Submitted That Met QC Criteria: September 7, 2005
• First Posted (Estimate): September 12, 2005

Study Record Updates

• Last Update Posted (Estimate): June 25, 2013
• Last Update Submitted That Met QC Criteria: June 21, 2013
• Last Verified: June 1, 2013

More Information

Terms related to this study

• Keywords: HIV; HIV-1; Treatment Experienced; Antiretroviral
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Antimetabolites; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Tenofovir; Lamivudine; Stavudine; Efavirenz
• Other Study ID Numbers: GS-99-903