title: Effect of suppressing HIV viremia on the HIV progression of patients undergoing a genotype resistance test after treatment failure.
abstract: BACKGROUND
  Treatment guidelines for multi-experienced HIV patients have recently evolved from aiming to preserve immunity to achieving virological success, largely due to the availability of new antiretroviral drugs and drug classes. To assess the role of viral suppression on clinical progression following a genotypic resistance test (GRT), we have examined a database on patients failing to respond to combined antiretroviral therapy (cART).
  
  
  METHODS
  Patients undergoing a GRT after failure to respond to cART between January 1999 and May 2006 were followed up to December 2006. Time-to-death or a new AIDS event/death were considered to be analysis end-points. Viral suppression (< 50 copies/ml [c/ml]) after GRT, a time-dependent covariate, was tested as predictor of disease progression.
  
  
  RESULTS
  Overall, 1,389 patients were included in this observational study. After the GRT, patients were followed up to 72 months (median 28 months, IQ range 13-51 months). During the follow-up, 124 patients (9%) died, and 86 (6%) experienced a new AIDS event. 774 patients (56%) achieved < 50 c/ml HIV-RNA. The results of an adjusted Cox model showed that undetectable HIV-RNA after the GRT was significantly associated with a lower risk of death (hazard ration [HR] 0.46, 95% confidence interval [CI] 0.27-0.76) and AIDS/death (HR 0.43, 95% CI 0.28-0.65). The adjusted hazard ratios suggested a twofold risk reduction. A threefold risk reduction of death related to achieved undetectable viral load was found in patients with resistance to more than one drug class and with CDC-C diagnosis; a fourfold reduction was found in patients with < 200 CD4+/mm(3).
  
  
  CONCLUSIONS
  Maximal viral suppression has a large impact on HIV progression, particularly in heavily pre-treated individuals. Our findings support the latest treatment guidelines, which have rapidly evolved from an initial lack of indication to suggestions, and finally to strong recommendations for achieving the goal of suppressing viremia.
authors.affiliation: Clinical Department, National Institute for Infectious Diseases Lazzaro Spallanzani, Via Portuense 292, 00149, Rome, Italy. zaccarelli@inmi.it
authors.forename: M
authors.initials: M
authors.lastname: Zaccarelli
authors.forename: P
authors.initials: P
authors.lastname: Lorenzini
authors.forename: V
authors.initials: V
authors.lastname: Tozzi
authors.forename: F
authors.initials: F
authors.lastname: Forbici
authors.forename: F
authors.initials: F
authors.lastname: Ceccherini-Silberstein
authors.forename: C
authors.initials: C
authors.lastname: Gori
authors.forename: R
authors.initials: R
authors.lastname: D'Arrigo
authors.forename: M P
authors.initials: MP
authors.lastname: Trotta
authors.forename: P
authors.initials: P
authors.lastname: Narciso
authors.forename: C F
authors.initials: CF
authors.lastname: Perno
authors.forename: A
authors.initials: A
authors.lastname: Antinori
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D015331:Cohort Studies; D018450:Disease Progression; D024921:Drug Resistance, Multiple, Viral / Q000235:genetics; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000401:mortality / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D007558:Italy; D008137:Longitudinal Studies; D008297:Male; D012189:Retrospective Studies; D017211:Treatment Failure; D019562:Viral Load; D014766:Viremia / Q000188:drug therapy* / Q000401:mortality / Q000821:virology
chemical_list: D019380:Anti-HIV Agents; D044966:Anti-Retroviral Agents