Inclusion Criteria:

• Age 18 years or older
• HIV-1 infection
• No prior antiretroviral therapy of any duration, including prior use to prevent perinatal transmission within prior six months.
• No prior chemotherapy or radiotherapy for KS
• Presence of Kaposi's sarcoma, documented by biopsy by the Pathology Department at Mulago Hospital, with at least one mucocutaneous lesion (including oral or genital mucosal lesions), each at least 0.6 x 0.6 cm in perpendicular diameters.
• Laboratory values obtained within 21 days prior to randomization: absolute neutrophil count equal to or more than 1000/mm3; hemoglobin > 9.0 g/dL; platelet count > 50,000/mm3; creatinine < 2 times upper limit of normal (ULN); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 5 times ULN; and alkaline phosphatase and total bilirubin < 2 times ULN.
• In women, negative urine pregnancy test within 28 days of randomization and just before randomization.
• If a woman of child-bearing potential (i.e., not yet reached menopause or undergone hysterectomy, bilateral oophorectomy, or tubal ligation), must be willing to use at least two of the following methods of contraception, to be provided by the study: condoms (male or female), IUD, or hormone-based therapy, e.g., contraceptive pills, Norplant or Depo-Provera.
• Candidate currently resides within Uganda and does not intend to relocate away from current geographical area of residence for the duration of study participation.
• Karnofsky performance score of 70 or more

Exclusion Criteria:

• Extensive degree of mucocutaneous KS, which would typically require chemotherapy or radiotherapy. This is defined by any of the following:

  • One or more bulky cutaneous lesions, defined as at least 5.0 cm in greatest diameter across the surface of the skin and at least 3 cm in height
  • One or more mucocutaneous lesions exhibiting ulceration
  • One or more oral lesions that interfere with swallowing

• Suggestion of pulmonary or gastrointestinal visceral KS, as evidenced by any of the following:

  • Abnormal chest x-ray within 21 days prior to randomization which is otherwise unexplained, unless the x-ray is unchanged compared with at least 60 days earlier
  • Positive occult blood stool testing within 21 days prior to randomization or history of overt bleeding from the mouth or rectum in the 21 days prior to randomization
• Facial lymphedema or lymphedema in any other body region which causes symptoms (e.g., pain) or functional disability (e.g., any less than 85% active range of motion in a large joint)
• Evidence of currently active, untreated opportunistic infection or malignancy (not including Kaposi's sarcoma); or unexplained temperature which is > 38.5 degrees C
• Use of drugs, within the prior 28 days, contraindicated while taking lopinavir/ritonavir or efavirenz because of effects on the cytochrome P450 system. These include propafenone, astemizole, terfenadine, rifampin, rifapentine, ergot derivatives, cisapride, lovastatin, simvastatin, pimozide, midazolam, and triazolam.
• Active drug or alcohol use that, in the investigators' opinion, would interfere with study participation
• Breastfeeding