The purpose of this study is to compare the effectiveness of treatment with tenofovir DF (TDF) plus lamivudine (3TC) plus efavirenz (EFV) with that of stavudine (d4T) plus 3TC plus EFV in HIV-infected patients who previously have not used anti-HIV drugs.

Patients will be stratified on the basis of HIV-1 RNA levels (greater than 100,000 copies/ml or less than or equal to 100,000 copies/ml) and CD4 count (less than 200 cells/mm3 or greater than or equal to 200 cells/mm3). Treatment-naive patients with HIV-1 RNA levels greater than 5,000 copies/ml will be randomized 1:1 to 1 of 2 treatment arms:

Group 1: TDF + d4T placebo + 3TC + EFV Group 2: TDF placebo + d4T + 3TC + EFV TDF/placebo and d4T/placebo will be administered in a blinded fashion. 3TC, EFV, and nevirapine (administered in the event of EFV-associated CNS toxicity) will be administered in open-label fashion. Patients will be monitored for safety using periodic physical examinations, serial laboratory tests, and bone densitometry tests. Additionally, changes in plasma HIV-1 RNA levels and CD4 cell counts will be monitored to assess antiviral efficacy. At the end of Week 48, patients without dose-limiting toxicity will have the option to roll over into open-label extended dosing until tenofovir DF is commercially available or Gilead Sciences terminates the study. Only open-label tenofovir DF will be provided beyond Week 48.

• Drug: Tenofovir disoproxil fumarate
• Drug: Efavirenz
• Drug: Lamivudine
• Drug: Stavudine

Inclusion Criteria

Patients may be eligible for this study if they:

• Are 18 to 65 years old.
• Are HIV-1 positive.
• Have HIV-1 RNA levels greater than 5,000 copies/ml within 28 days of screening visit.
• Agree to use effective methods of birth control during study and for 30 days after study ends.

Exclusion Criteria

Patients will not be eligible for this study if they:

• Are unable to take medications by mouth.
• Have chronic nausea or vomiting.
• Have cancer, other than skin cancer.
• Have had active, serious infections requiring antibiotic shots within 15 days prior to screening.
• Are taking probenecid, systemic corticosteroids, interleukin-2 (IL-2), experimental drugs (unless approved by Gilead Sciences), drugs that are harmful to the kidneys, or drugs that interact with efavirenz.
• Are receiving chemotherapy.
• Have been diagnosed with an AIDS-defining condition.
• Have had significant kidney or bone disease.
• Have ever taken certain anti-HIV drugs.
• Have had chemotherapy or immunizations within 30 days of beginning of study.
• Are pregnant or breast-feeding.
• Have a condition which may affect the ability to participate in this study, such as alcohol or substance abuse.
• Have received, or expect to receive, treatment for Kaposi's sarcoma.