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.

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.