Safety and Effectiveness of Tenofovir Disoproxil Fumarate (Tenofovir DF) Plus Other Anti-HIV Drugs in HIV-Infected Patients

A Phase III, Double-Blind, Randomized, Placebo-Controlled, Multicenter Study of the Safety and Efficacy of Tenofovir Disoproxil Fumarate in Combination With Other Antiretroviral Agents for the Treatment of HIV-1 Infected Patients

The purpose of this study is to see if giving tenofovir DF plus a combination of other anti-HIV drugs is safe and effective.

Patients are randomized 2:1 to add tenofovir DF once daily or placebo to their existing antiretroviral regimen in a blinded manner. Patients are stratified according to HIV-1 RNA level, CD4 cell count, and number of antiretroviral drugs taken prior to study entry. Patients and physicians are strongly discouraged from making changes in their antiviral therapies for at least 24 weeks post-randomization. After Week 24, changes in background antiretroviral therapy are permitted. At 24 weeks post-randomization, patients randomized to receive placebo are crossed over to receive open-label tenofovir DF once daily for the remainder of the 48-week study. While on study drug, patients are monitored for safety using periodic physical examinations and serial laboratory tests. Additionally, changes in plasma HIV RNA levels and CD4 cell counts are monitored to assess antiviral efficacy. At the end of the 48-week study period, patients are rolled over into extended dosing until tenofovir DF is commercially available or Gilead Sciences terminates the study.

Inclusion Criteria

Patients may be eligible for this study if they:

• Are HIV-positive.
• Have been on stable anti-HIV therapy for at least 8 weeks with no more than 4 anti-HIV drugs at the time of study entry.
• Have a viral load (level of HIV in the blood) between 400 and 10,000 copies/ml.
• Have good kidney function.
• Are 18 to 65 years old.
• Agree to use a barrier method of birth control (such as condoms) during the study and for 30 days after.

Exclusion Criteria

Patients will not be eligible for this study if they:

• Have a new AIDS-related illness diagnosed within 30 days of study entry.
• Have any other serious medical conditions, including kidney or bone disease, an active infection requiring antibiotics, or cancer (other than Kaposi's sarcoma or certain skin cancers).
• Have received a vaccine within 30 days of study entry.
• Are unable to take medications by mouth.
• Have ever taken tenofovir or adefovir dipivoxil.
• Have taken certain medications within 30 days of study entry, such as chemotherapy, corticosteroids, medications that affect the kidneys, treatment for Kaposi's sarcoma, or certain experimental drugs.
• Abuse alcohol or drugs.
• Are pregnant or breast-feeding.