The use of antiretroviral (ARV) medications has greatly improved morbidity and mortality of HIV-infected patients but long-term use of these agents has been associated with significant toxicities and medication fatigue that can lead to problems with adherence and eventual development of virologic resistance. The spectrum of ARV toxicities is broad including the development of lipodystrophy syndrome with lipid abnormalities and glucose intolerance or diabetes, while increasing evidence suggests an increased risk of cardiovascular complications in ARV-treated HIV-infected individuals. Current PHHS treatment guidelines recommend deferring ARV treatment initiation in asymptomatic HIV-infected individuals with CD4 count greater than or equal to 350 cells/micro liter, and treatment initiation after the CD4 count is less than 350 cells/micro liter. Several patients who started antiretroviral therapy at higher CD4 counts (based on older treatment initiation guidelines) or have experienced significant immunologic reconstitution after ARV initiation, elect to interrupt antiretroviral therapy until their CD4 count reaches the level of current recommendations for therapy initiation (less than 350 cells/micro liter). Studies to date suggest that baseline and nadir CD4 count are the best predictors of a longer duration of treatment interruption that may be more beneficial with respect to reversal or delay of long-term ARV-associated toxicity and improved quality of life. It is known that intermittent cycles of IL-2 administration can lead to expansion of the CD4 pool and prolong survival of CD4 T cells. In this study the hypothesis tested is that IL-2 given prior to ARV treatment interruption could significantly prolong the period of ARV treatment interruption with preservation of CD4 counts above 350 cells/micro liter, and that this prolongation will be beneficial with respect to antiretroviral related toxicity and quality of life. The study will have two parts: during the first part (24 weeks) patients will be randomized 1:1 to either receive three cycles or IL-2 with their ARV therapy or ARV therapy alone. In the second part (week 24 to week 120), all participants will interrupt therapy and restart when CD4 is less than 350 cells/micro liter. The main comparison will be at week 72, when the proportion of patients from the two groups who remain off drugs and have a CD4 greater than 350 cells/micro liter will be compared. At regular intervals (every 24 weeks) lipodystrophy measurements and quality of life questionnaires will be evaluated.
* INCLUSION CRITERIA: Age greater than or equal to 18 years. HIV-1 infection confirmed by ELISA and Western Blot before screening. Category A or B HIV-1 infection. Antiretroviral treatment: * started at least 12 months prior to screening visit; * stable and continuous for at least 12 weeks prior to screening visit; * modified no more than once for virologic failure. IL-2 naive CD-4(+) T-lymphocyte count greater than or equal to 500 cells/mm(3) in the twelve weeks prior to screening (historical) and at screening. Nadir CD4(+) T-lymphocyte count greater than or equal to 200 cells/mm(3) prior to screening visit (that is, no measurement whose values may be less than 200/mm(3) since diagnosis of the HIV infection. Plasma HIV RNA less than 50 copies/ml in the 12 weeks preceding screening (historical, less than limit of detection if different method and/or cut off used) and at screening. For women of child-bearing age: use of effective contraception (hormonal such as birth control pill or injections, intrauterine device, surgical sterilization and/or mechanical barrier methods such as diaphragm or condoms); for all participants agreement to fully comply with prevention of transmission recommendations during periods of viremia if sexually active (latex condoms with or without additional barrier methods). Desire to interrupt antiretroviral therapy. Ability to sign informed consent (no later than W-2). EXCLUSION CRITERIA: Previous treatment with IL-2. Combined treatment with interferon, other interleukins, anti-HIV vaccines, systemic (not topical or inhaled) corticosteroids and hydroxyurea within the previous 12 weeks. Diagnosis of AIDS. Acute infection in the 14 days preceding inclusion. Pregnant, lactating woman desiring conception or not using contraception. Hemoglobin less than 10 g/dl; neutrophils less than 1,000/mm(3); platelets less than 50,000/mm(3); creatinine greater than 1.5 times the upper limit of normal (N); bilirubin greater than 3N; AST or ALT greater than 3 N. Progressive disease of malignant, psychiatric, cardiac, pulmonary, thyroid, renal or neurological (peripheral or central) origin or severe disorders of hemostasis. Severe uncontrolled hypertension. Previous or progressive pathology contraindicating the administration of IL-2. History of extensive psoriasis, Crohn's disease or auto-immune disease involving severe complications. HTLV-1 infection (ELISA positive). Hepatitis B virus co-infection treated with lamivudine or tenofovir or adefovir. Since atazanavir use can be associated with higher bilirubin levels (mostly indirect) in the absence of clinical consequences, subjects on atazanavir with bilirubin up to 4.5 times N may be allowed to participate if the levels have been stable and after approval by the PI or the PI designated covering physician.
are designated in this study