9TH EUROPEAN AIDS CONFERENCE (EACS)
1st EACS RESISTANCE & PHARMACOLOGY WORKSHOP

 October 25 - 29, 2003 Warsaw • Poland

18.4 Morbidity/Mortality in the Era of HAART

 F9/6 - CHANGING INCIDENCE OF CENTRAL NERVOUS SYSTEM (CNS) AIDS-RELATED DISEASES IN THE EUROSIDA COHORT
* d'Arminio Monforte A.1, Cinque P.2, Mocroft A.3, Goebel F.-D.4, Antunes F.5, Katlama C.6, Justesen U.S.7, Vella S.8, Kirk O.9, Lundgren J.D.9, for the EuroSida Study Group
  1 Inst of Infect and Trop Dis, Univ of Milan, Italy,2 Clin of Infect Dis, San Raffaele Hosp, Milan, Italy,3 Royal Free & Univ College Med School, London, UK,4 Klin Innerstadt Medizin Polikl, München, Germany,5 Depart of Infect Dis, Hosp Santa Maria, Lisbon, Portugal,6 Dept de Med Tropic, Hosp Pitié-Salpêtriére, Paris, France,7 Dept of Infect Dis, Odense Univ Hosp, Odense, Denmark,8 Lab of Virol, Ist Super San, Rome, Italy,9 Dept 044, Hvidovre Univ H, Hvidovre, Denmark
 

Objective: To assess the trend of incidence of CNS diseases (CNS-D) among 9,803 patients within EuroSIDA during 1994-2002.

Methods: All patients without CNS-D at recruitment were included. Incidences were calculated using a person-years (py) analysis, Cox models were used to investigate progression to CNS-D, either separately (AIDS Dementia Complex, ADC and opportunistic CNS diseases, CNS-OIs) or as a whole.

Results: Overall, 568 patients (5.8%) were diagnosed with a new CNS-D. Incidence decreased significantly from 5.9 per 100 py in 1994 to 0.5 in 2002. The decrease was 40% per calendar year, it was similar to that of non-CNS-D and less evident after year 1998. The annual decrease rate was significantly higher in ADC than in CNS OIs (45% vs. 37%). In multivariable models, low CD4 cell count and high plasma viral load, but not calendar year, HAART or any components thereof, were significantly associated with development of CNS-D, indicating that the effect of HAART was likely mediated by improved immunological status and inhibition of viral replication. In contrast, use of NRTIs, irrespective of use of PIs or NNRTIs, appeared to protect specifically against ADC (RH=0.59, 95%-CI: 0.39-0.90), but not against other CNS-D (RH=1.06, 95%-CI: 0.80-1.40), suggesting that, in ADC, therapy might have a direct, additive effect in the CNS.

Relative risk of any CNS-D after recruitment to the EuroSIDA study.
  Univariable model  P/value  Multivariable model*  P/value 
  RH and 95%-CI    RH and 95%-CI   
CD4 cell count (per 50% higher)  0.60 (0.58-0.62)  <0.0001  0.57 (0.53-0.62)  <0.0001 
HIV/RNA (per 1 log higher)  2.29 (2.02-2.60)  <0.0001  1.43 (1.22-1.65)  <0.0001 
Started NRTIs  1.08 (0.86-1.35)  0.51  0.94 (0.62-1.43)  0.76 
Started PI-HAART  0.36 (0.29-0.45)  <0.0001  0.93 (0.65-1.35)  0.71 
Started NNRTI-HAART  0.59 (0.42-0.82)  0.0016  0.77 (0.48-1.22)  0.26 
Model with time-dependent variables. *: model also adjusted for calendar year and HIV transmission category.

Conclusions: The incidence of CNS-D across Europe decreased following the introduction of HAART, immune reconstitution being the main responsible. A direct effect of antiretroviral therapy on virus replication in CNS might have also accounted for the incidence decline in ADC.

Presenting Author: Prof Antonella d'Arminio-Monforte, Institute of Infectious and Tropical Diseases, University of Milan, italy, L Sacco Hospital, via GB Grassi 74, 20157 Milan, Italy, 20157, Milan, Italy, Phone: +39 02 3560010

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