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.

Study Overview
=================
Brief Summary
-----------------
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.

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.

Official Title
-----------------
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)

Conditions
-----------------
HIV Infections

Intervention / Treatment
-----------------
* Drug: Viread (tenofovir disoproxil fumarate)
* Drug: Sustiva (Efavirenz)
* Drug: Epivir (Lamivudine)
* Drug: Zerit (Stavudine) Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Viread (tenofovir disoproxil fumarate)|Tenofovir DF 300 mg tablets once daily|
|Drug: Sustiva (Efavirenz)|efavirenz capsules 600 mg once daily|
|Drug: Epivir (Lamivudine)|lamivudine 150 mg tablets twice daily|
|Drug: Zerit (Stavudine) Placebo|stavudine placebo capsules twice daily|

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
HIV, Antiretroviral, Treatment Experienced, HIV-1