title: Risk of clinical progression among patients with immunological nonresponse despite virological suppression after combination antiretroviral treatment.
abstract: BACKGROUND
  It is unclear whether lack of immunological response despite viral suppression and relatively preserved CD4 T-cell count is associated with increased risk of AIDS or severe non-AIDS events.
  
  
  METHODS
  Patients initiating first combination antiretroviral therapy (cART) were studied from first viral load 80  copies/ml or less up to AIDS, serious non-AIDS events (malignancies, severe infections, acute kidney injury, cardiovascular events, liver decompensation) or death. Follow-up was right censored if viral load was more than 500. Immunological nonresponse (INR) was defined as current CD4 cell count less than 120% pre-cART. A Poisson regression analysis was used to investigate the association between INR and the outcome.
  
  
  RESULTS
  Three thousand, three hundred and seventy-eight patients were followed for a median of 32 months (interquartile range: 15-67). Two hundred and twenty-two events (32 deaths, 39 AIDS-defining events, 48 malignancies, 32 severe infections, 47 acute kidney injuries, 12 cardiovascular events, 12 other nonfatal events) were observed. The rate of clinical events among INR and immunological responders was 4.41 [95% confidence interval (CI) 3.38-5.74] and 1.84 (95% CI 1.58-2.15) per 100 person years of follow-up, respectively, accounting for a crude rate ratio of 2.39 (95% CI 1.77-3.25; P < 0.001). INR remained an independent predictor of clinical progression after adjusting for baseline characteristics, including pre-cART CD4 cell count (adjusted rate ratio 2.93; 95% CI 2.06-4.16, P < 0.001) or current CD4 cell count (adjusted rate ratio 1.94; 95% CI 1.39-2.72, P < 0.001). The association did not vary by pre-cART CD4 cell counts (P for interaction = 0.93)
  
  
  CONCLUSIONS
  INR are at higher risk of severe clinical events than responders. The association was consistent across different CD4 cell counts at cART initiation and was only partially explained by current CD4 cell count. INR could be a marker of immune system malfunctioning, not completely captured by absolute CD4 cell count.
authors.affiliation: Clinic of Infectious Diseases, San Gerardo de' Tintori Hospital, Monza, Italy. g.lapadula@hsgerardo.org
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lapadula
authors.forename: Alessandro
authors.initials: A
authors.lastname: Cozzi-Lepri
authors.forename: Giulia
authors.initials: G
authors.lastname: Marchetti
authors.forename: Andrea
authors.initials: A
authors.lastname: Antinori
authors.forename: Alessandro
authors.initials: A
authors.lastname: Chiodera
authors.forename: Emanuele
authors.initials: E
authors.lastname: Nicastri
authors.forename: Giustino
authors.initials: G
authors.lastname: Parruti
authors.forename: Massimo
authors.initials: M
authors.lastname: Galli
authors.forename: Andrea
authors.initials: A
authors.lastname: Gori
authors.forename: Antonella d'Arminio
authors.initials: Ad
authors.lastname: Monforte
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000276:immunology / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018450:Disease Progression; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D007558:Italy; D008297:Male; D011446:Prospective Studies; D012044:Regression Analysis; D012307:Risk Factors; D013997:Time Factors; D019562:Viral Load
chemical_list: D044966:Anti-Retroviral Agents