title: Short-cycle structured intermittent treatment of chronic HIV infection with highly active antiretroviral therapy: effects on virologic, immunologic, and toxicity parameters.
abstract: Although continuous highly active antiretroviral therapy (HAART) is effective for many HIV-infected patients, it can be toxic and prohibitive in cost. By decreasing the total amount of time patients receive medications, intermittent HAART could reduce toxicity and cost. Therefore, we initiated a pilot study in which 10 HIV-infected individuals receiving effective therapy that resulted in levels of HIV RNA <50 copies per ml of plasma and CD4(+) T cell counts >300 cells per mm(3) of whole blood received repeated cycles of 7 days on HAART followed by 7 days off of HAART. Patients maintained suppression of plasma viremia for 32-68 weeks. There was no significant increase in HIV proviral DNA or replication-competent HIV in peripheral CD4(+) T cells or HIV RNA in peripheral blood or lymph node mononuclear cells. There was no significant change in CD4(+) T cell counts, no significant increase in CD4(+) or CD8(+) T cells expressing activation markers or producing IFN-gamma in response to HIV, no increase in CD4(+) T cell proliferation to p24 antigen, and no evidence for the development of resistance to HAART medications. There was a significant decrease in serum cholesterol and triglyceride levels. Thus, in this proof-of-concept study, short-cycle intermittent HAART maintained suppression of plasma viremia as well as HIV replication in reservoir sites while preserving CD4(+) T cell counts. In addition, there was a decrease in serum cholesterol and triglyceride levels. Intermittent therapy may be an important strategy to reduce cost and toxicity for HIV-infected individuals.
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. mdybul@nih.gov
authors.forename: M
authors.initials: M
authors.lastname: Dybul
authors.forename: T W
authors.initials: TW
authors.lastname: Chun
authors.forename: C
authors.initials: C
authors.lastname: Yoder
authors.forename: B
authors.initials: B
authors.lastname: Hidalgo
authors.forename: M
authors.initials: M
authors.lastname: Belson
authors.forename: K
authors.initials: K
authors.lastname: Hertogs
authors.forename: B
authors.initials: B
authors.lastname: Larder
authors.forename: R L
authors.initials: RL
authors.lastname: Dewar
authors.forename: C H
authors.initials: CH
authors.lastname: Fox
authors.forename: C W
authors.initials: CW
authors.lastname: Hallahan
authors.forename: J S
authors.initials: JS
authors.lastname: Justement
authors.forename: S A
authors.initials: SA
authors.lastname: Migueles
authors.forename: J A
authors.initials: JA
authors.lastname: Metcalf
authors.forename: R T
authors.initials: RT
authors.lastname: Davey
authors.forename: M
authors.initials: M
authors.lastname: Daucher
authors.forename: P
authors.initials: P
authors.lastname: Pandya
authors.forename: M
authors.initials: M
authors.lastname: Baseler
authors.forename: D J
authors.initials: DJ
authors.lastname: Ward
authors.forename: A S
authors.initials: AS
authors.lastname: Fauci
mesh_terms: D019380:Anti-HIV Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D018791:CD4 Lymphocyte Count; D004334:Drug Administration Schedule; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000302:isolation & purification; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008826:Microbial Sensitivity Tests; D010641:Phenotype; D010865:Pilot Projects; D012367:RNA, Viral
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral