title: Disease-modifying therapeutic concepts for HIV in the era of highly active antiretroviral therapy.
abstract: Chronic HIV infection is associated with persistent immune activation and inflammation even among patients virologically suppressed on antiretroviral therapy for years. Chronic immune activation has been associated with poor outcomes--both AIDS-defining and non-AIDS-defining clinical events--and persistent CD4 T-cell depletion. The cause of chronic immune activation in well-controlled HIV infection is unknown. Proposed drivers include residual viral replication, microbial translocation, and coinfecting pathogens. Therapeutic interventions targeting immune activation are emerging, from approaches that interfere directly with activation and inflammatory pathways to those that prevent microbial translocation or decrease the availability of host target cells for the virus. In the context of the disappointing results of the interleukin-2 trials, the main challenges to developing these disease-modifying therapies include identifying an adequate target population and choosing surrogate endpoints that will provide positive proof-of-concept that the interventions will translate into long-term clinical benefit before embarking on large clinical endpoint trials.
authors.affiliation: Infectious Diseases Group, Pfizer Global Research and Development, Sandwich, United Kingdom. scott.butler@pfizer.com
authors.forename: Scott L
authors.initials: SL
authors.lastname: Butler
authors.forename: Hernan
authors.initials: H
authors.lastname: Valdez
authors.forename: Michael
authors.initials: M
authors.lastname: Westby
authors.forename: Manos
authors.initials: M
authors.lastname: Perros
authors.forename: Carl H
authors.initials: CH
authors.lastname: June
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Jacobson
authors.forename: Yves
authors.initials: Y
authors.lastname: Levy
authors.forename: David A
authors.initials: DA
authors.lastname: Cooper
authors.forename: Daniel
authors.initials: D
authors.lastname: Douek
authors.forename: Michael M
authors.initials: MM
authors.lastname: Lederman
authors.forename: Pablo
authors.initials: P
authors.lastname: Tebas
mesh_terms: D019380:Anti-HIV Agents / Q000008:administration & dosage*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D002986:Clinical Trials as Topic; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage*
chemical_list: D019380:Anti-HIV Agents; D007155:Immunologic Factors