title: Intensification and stimulation therapy for human immunodeficiency virus type 1 reservoirs in infected persons receiving virally suppressive highly active antiretroviral therapy.
abstract: Highly active antiretroviral therapy (HAART) has led to significant changes in mortality and morbidity in the human immunodeficiency virus type 1 (HIV-1) epidemic. Nevertheless, because of molecular mechanisms of viral persistence, HAART does not eradicate HIV-1. Didanosine and hydroxyurea were added to the antiretroviral regimens of 3 HIV-1-infected men who were receiving stable HAART and who had HIV-1 RNA levels <50 copies/mL at the initiation of the study protocol, as a novel intensification to attack cryptic viral replication; low-dose OKT3 was then administered, followed by a course of interleukin-2, to stimulate latent provirus. Replication-competent virus was undetectable after treatment, and plasma viral RNA was either undetectable or <5 copies/mL. In trial periods during which no antiretroviral therapy was administered, the patients developed plasma viral rebound. This translational approach combines novel intensification and stimulation therapy to deplete residual HIV-1 reservoirs. Additional experimental approaches must be developed if HIV-1 eradication is to become possible in patients receiving virally suppressive HAART.
authors.affiliation: Dorrance Hamilton Laboratories, Center for Human Virology, Division of Infectious Diseases, Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Kulkosky
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Nunnari
authors.forename: Miguel
authors.initials: M
authors.lastname: Otero
authors.forename: Sandra
authors.initials: S
authors.lastname: Calarota
authors.forename: Geetha
authors.initials: G
authors.lastname: Dornadula
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.forename: Anne
authors.initials: A
authors.lastname: Malin
authors.forename: Julie
authors.initials: J
authors.lastname: Sullivan
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.forename: Joseph
authors.initials: J
authors.lastname: DeSimone
authors.forename: Timothy
authors.initials: T
authors.lastname: Babinchak
authors.forename: John
authors.initials: J
authors.lastname: Stern
authors.forename: Winston
authors.initials: W
authors.lastname: Cavert
authors.forename: Ashley
authors.initials: A
authors.lastname: Haase
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Pomerantz
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D007109:Immunity / Q000187:drug effects; D008297:Male
chemical_list: D019380:Anti-HIV Agents