Immunologic and Virologic Studies of Intermittent Versus Continuous HAART in the Treatment of HIV Disease

Study start date: November 1, 1999

INCLUSION CRITERIA: Documentation of HIV-1 infection by licensed ELISA test kit and confirmed by a second method (e.g. Western Blot). Absolute CD4+ T-cell count of greater than or equal to 300/mm(3) within 30 days before randomization (For patients who are status post-splenectomy, also CD4+ T-cell greater than 20%). For patients in cohort 2, the lowest documented CD4+ T-cell count must be greater than or equal to 200 cells/mm(3). Receiving HAART (at least 2 NRTIs and an NNRTI or a PI) with at least 1 viral load test below the limit of detection (at least less than 500 copies/ml) greater than or equal to 3 months for cohort 1 and 4 and greater than or equal to 6 months for cohorts 2, 3 and 5 before screening. A confirmatory viral load of less than 50 copies/ml prior to enrollment. Age at least 18 years. For women of childbearing potential, a negative pregnancy test (serum or urine) is required within 14 days prior to randomization. Laboratory values (within 30 days prior to randomization): AST no more than 5 times the upper limit of normal (ULN); Total or direct bilirubin no more than 2 times the ULN unless there is a pattern consistent with Gilbert's syndrome or the patient is receiving indinavir; Creatinine no more than 2.0 mg/dL; Platelet count at least 50,000 microliters. Willingness to provide blood samples for storage that may be used in future studies of HIV infection and/or immunopathogenesis. EXCLUSION CRITERIA: Concurrent malignancy, or any other disease state, requiring cytotoxic chemotherapy . Symptomatic for significant HIV-related illnesses, such as opportunistic infections and malignancies other than mucocutaneous Kaposi's sarcoma . Use of experimental antiretrovirals less than or equal to 6 months prior to enrollment. An exception may be made for hydroxyurea according to the judgment of the Principal Investigator. For cohort 1 and the extension of cohort 2, current use of IL-2 or history of use of IL-2 . Cohorts 2, 3, 4 and 5, patients must not be currently receiving cycles of IL-2. For the extension of cohort 2, participation in previous STI studies or off HAART for greater than 2 weeks consecutively in the last year. Pregnancy or breastfeeding during the study period. Significant cardiac, pulmonary, kidney, rheumatologic, gastrointestinal, or CNS disease as detectable on routine history, physical examination, or screening laboratory studies are excluded. If an abnormality is a contraindication to a specific drug, an alternative drug within the same class may be used. Psychiatric illness that, in the opinion of the PI, might interfere with study compliance. Active substance abuse or history of prior substance abuse that may interfere with protocol compliance or compromise patient safety. Refusal to practice safe sex or use precautions against pregnancy (effective birth control or abstinence). Known history or laboratory evidence of chronic hepatitis B infection including surface antigen positivity . Patients not receiving salvage HAART, i.e. no evidence of clinical resistance to licensed antiretrovirals. Patients in cohort 1 cannot be receiving nevirapine at the time of enrollment. Patients receiving nevirapine or abacavir at time of enrollment. Expanded access medications are not allowed at time of enrollment nor while on study.