title: Timely HAART initiation may pave the way for a better viral control.
abstract: BACKGROUND
  When to initiate antiretroviral therapy in HIV infected patients is a difficult clinical decision. Actually, it is still a matter of discussion whether early highly active antiretroviral therapy (HAART) during primary HIV infection may influence the dynamics of the viral rebound, in case of therapy interruption, and overall the main disease course.
  
  
  METHODS
  In this article we use a computational model and clinical data to identify the role of HAART timing on the residual capability to control HIV rebound after treatment suspension. Analyses of clinical data from three groups of patients initiating HAART respectively before seroconversion (very early), during the acute phase (early) and in the chronic phase (late), evidence differences arising from the very early events of the viral infection.
  
  
  RESULTS
  The computational model allows a fine grain assessment of the impact of HAART timing on the disease outcome, from acute to chronic HIV-1 infection. Both patients' data and computer simulations reveal that HAART timing may indeed affect the HIV control capability after treatment discontinuation. In particular, we find a median time to viral rebound that is significantly longer in very early than in late patients.
  
  
  CONCLUSIONS
  A timing threshold is identified, corresponding to approximately three weeks post-infection, after which the capability to control HIV replication is lost. Conversely, HAART initiation occurring within three weeks from the infection could allow to preserve a significant control capability. This time could be related to the global triggering of uncontrolled immune activation, affecting residual immune competence preservation and HIV reservoir establishment.
authors.affiliation: Biomedical University Campus, via Alvaro del Portillo 21, Rome, Italy. p.paci@iac.cnr.it
authors.forename: Paola
authors.initials: P
authors.lastname: Paci
authors.forename: Federico
authors.initials: F
authors.lastname: Martini
authors.forename: Massimo
authors.initials: M
authors.lastname: Bernaschi
authors.forename: Gianpiero
authors.initials: G
authors.lastname: D'Offizi
authors.forename: Filippo
authors.initials: F
authors.lastname: Castiglione
mesh_terms: D019380:Anti-HIV Agents / Q000008:administration & dosage*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D003198:Computer Simulation; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents