title: Risk of Severe Non AIDS Events Is Increased among Patients Unable to Increase their CD4+ T-Cell Counts >200+/μl Despite Effective HAART.
abstract: BACKGROUND
  Immunological non-response (INR) despite virological suppression is associated with AIDS-defining events/death (ADE). Little is known about its association with serious non-AIDS-defining events (nADE).
  
  
  METHODS
  Patients highly-active antiretroviral therapy (HAART) with <200 CD4+/μl and achieving HIV-RNA <50 copies/ml within 12 (±3) months were categorized as INR if CD4+ T-cell count at year 1 was <200/μl. Predictors of nADE (malignancies, severe infections, renal failure--ie, estimated glomerular filtration rate <30 ml/min, cardiovascular events and liver decompensation) were assessed using multivariable Cox models. Follow-up was right-censored in case of HAART discontinuation or confirmed HIV-RNA>50.
  
  
  RESULTS
  1221 patients were observed for a median of 3 (IQR: 1.3-6.1) years. Pre-HAART CD4+ were 77/μl (IQR: 28-142) and 56% of patients had experienced an ADE. After 1 year, CD4+ increased to 286 (IQR: 197-387), but 26.1% of patients were INR. Thereafter, 86 nADE (30.2% malignancies, 27.9% infectious, 17.4% renal, 17.4% cardiovascular, 7% hepatic) were observed, accounting for an incidence of 1.83 events (95%CI: 1.73-2.61) per 100 PYFU. After adjusting for measurable confounders, INR had a significantly greater risk of nADE (HR 1.65; 95%CI: 1.06-2.56). Older age (per year, HR 1.03; 95%CI: 1.01-1.05), hepatitis C co-infection (HR 2.09; 95%CI: 1.19-3.7), a history of previous nADE (HR 2.16; 95%CI: 1.06-4.4) and the occurrence of ADE during the follow-up (HR 2.2; 95%CI: 1.15-4.21) were other independent predictors of newly diagnosed nADE.
  
  
  CONCLUSIONS
  Patients failing to restore CD4+ to >200 cells/μl run a greater risk of serious nADE, which is intertwined or predicted by AIDS progression. Improved management of this fragile population and innovative therapy able to induce immune-reconstitution are urgently needed. Also, our results strengthen the importance of earlier diagnosis and HAART introduction.
authors.affiliation: Clinic of Infectious Diseases, "San Gerardo de' Tintori" Hospital, Monza, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lapadula
authors.affiliation: IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy.
authors.forename: Liliane
authors.initials: L
authors.lastname: Chatenoud
authors.affiliation: Clinic of Infectious Diseases, "San Gerardo de' Tintori" Hospital, Monza, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Gori
authors.affiliation: University Division of Infectious and Tropical Diseases, University of Brescia, Brescia, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Castelli
authors.affiliation: Clinic of Infectious Diseases, "Sacro Cuore" Catholic University of Rome, Rome, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Di Giambenedetto
authors.affiliation: Clinic of Infectious Diseases, "Sacro Cuore" Catholic University of Rome, Rome, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Fabbiani
authors.affiliation: Clinic of Infectious Diseases, Ospedali Riuniti, Bergamo, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Maggiolo
authors.affiliation: University Division of Infectious and Tropical Diseases, University of Brescia, Brescia, Italy.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Focà
authors.affiliation: Clinic of Infectious Diseases, Ospedale Policlinico, Bari, Italy.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Ladisa
authors.affiliation: Clinic of Infectious Diseases, Ospedale Sant'Anna, Ferrara, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Sighinolfi
authors.affiliation: Clinic of Infectious Diseases, Ospedale S.M. Annunziata, Florence, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Di Pietro
authors.affiliation: Clinic of Infectious Diseases, Istituti Ospitalieri, Cremona, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Pan
authors.affiliation: University Division of Infectious and Tropical Diseases, University of Brescia, Brescia, Italy; Unit of Infectious Diseases, Department of Medical and Surgical Sciences, University "Magna Graecia", Catanzaro, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Torti
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D018791:CD4 Lymphocyte Count; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000209:etiology; D060085:Coinfection / Q000453:epidemiology / Q000209:etiology; D015897:Comorbidity; D018450:Disease Progression; D005260:Female; D006801:Humans; D008107:Liver Diseases / Q000453:epidemiology / Q000209:etiology; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology / Q000209:etiology; D012307:Risk Factors; D019562:Viral Load / Q000187:drug effects*