title: A randomized trial of interleukin-2 during withdrawal of antiretroviral treatment.
abstract: In HIV-infected individuals on antiretroviral treatment with viral suppression, structured treatment interruptions are designed to allow exposure to endogenous HIV antigens and to thereby boost HIV-specific immunity. AIDS Clinical Trials Group A5132 was an exploratory 2-arm randomized trial that evaluated two 4-week treatment interruptions in combination with 2 strategies for administering interleukin-2 (IL-2): 2.0 million international units of IL-2 subcutaneously daily during the final 2 weeks of treatment interruption and the first week of treatment reinitiation (arm A), or 4.5 million international units of IL-2 subcutaneously twice a day during the first 5 days of treatment reinitiation (arm B). Twenty-one subjects with HIV-1 RNA <50 copies/mL and CD4+ T cell counts ≥300 (median 615) cells/mm(3) were randomized. The primary endpoint was the viral setpoint measured 11-12 weeks after a third treatment interruption (observed for 7 Arm A and 9 Arm B). The median HIV-1 RNA setpoints were 4.3 and 4.5 log(10) copies/mL for Arm A and Arm B, respectively; there was no evidence of a difference between arms (P = 0.50, rank-sum test, worst rank for unobserved viral setpoint). The current study, the first to evaluate IL-2 during repeated short-term treatment interruptions, revealed no evidence for augmentation of HIV immunity. Viral setpoints were similar to historical controls, emphasizing the need for new strategies to enhance HIV-specific immunity.
authors.affiliation: Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, MA 02115, USA. rbosch@hsph.harvard.edu
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Bosch
authors.forename: Richard B
authors.initials: RB
authors.lastname: Pollard
authors.forename: Alan
authors.initials: A
authors.lastname: Landay
authors.forename: Evgenia
authors.initials: E
authors.lastname: Aga
authors.forename: Lawrence
authors.initials: L
authors.lastname: Fox
authors.forename: Ronald
authors.initials: R
authors.lastname: Mitsuyasu
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D023241:Antiretroviral Therapy, Highly Active; D002985:Clinical Protocols; D005260:Female; D005500:Follow-Up Studies; D006678:HIV / Q000472:pathogenicity / Q000502:physiology*; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D006801:Humans; D007167:Immunotherapy; D007376:Interleukin-2 / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000032:analysis*; D014779:Virus Replication; D028761:Withholding Treatment
chemical_list: D000276:Adjuvants, Immunologic; D007376:Interleukin-2; D012367:RNA, Viral