Immuno-virological discordance and the risk of non-AIDS and AIDS events in a large observational cohort of HIV-patients in Europe.
BACKGROUND
The impact of immunosuppression despite virological suppression (immuno-virological discordance, ID) on the risk of developing fatal and non-fatal AIDS/non-AIDS events is unclear and remains to be elucidated.


METHODS
Patients in EuroSIDA starting at least 1 new antiretroviral drug with CD4<350 cells/µl and viral load (VL)>500 copies/mL were followed-up from the first day of VL< = 50 copies/ml until a new fatal/non-fatal non-AIDS/AIDS event. Considered non-AIDS events included non-AIDS malignancies, pancreatitis, severe liver disease with hepatic encephalopathy (>grade 3), cardio- and cerebrovascular events, and end-stage renal disease. Patients were classified over time according to whether current CD4 count was above (non-ID) or below (ID) baseline level. Relative rates (RR) of events were calculated for ID vs. non-ID using adjusted Poisson regression models.


RESULTS
2,913 patients contributed 11,491 person-years for the analysis of non-AIDS. 241 pre-specified non-AIDS events (including 84 deaths) and 89 AIDS events (including 10 deaths) occurred. The RR of developing pre-specified non-AIDS events for ID vs. non-ID was 1.96 (95% CI 1.37-2.81, p<0.001) in unadjusted analysis and 1.43 (0.94-2.17, p = 0.095) after controlling for current CD4 count. ID was not associated with the risk of AIDS events (aRR 0.76, 95% CI 0.41-1.38, p = 0.361).


CONCLUSIONS
Compared to CD4 responders, patients with immuno-virological discordance may be at increased risk of developing non-AIDS events. Further studies are warranted to establish whether in patients with ID, strategies to directly modify CD4 count response may be needed besides the use of ART.
Department of Medicine I, Infectious Diseases Unit, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Alexander
A
Zoufaly
Department of Infection and Population Health, University College London, London, United Kingdom.
Alessandro
A
Cozzi-Lepri
Department of Infection and Population Health, University College London, London, United Kingdom.
Joanne
J
Reekie
Copenhagen HIV Programme - Department of Infectious Diseases and Rheumatology, section 8632, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Ole
O
Kirk
Copenhagen HIV Programme - Department of Infectious Diseases and Rheumatology, section 8632, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Jens
J
Lundgren
University of Amsterdam, Academic Medical Center, Department of Global Health, and Stichting HIV Monitoring, Amsterdam, Netherlands.
Peter
P
Reiss
University of Belgrade School of Medicine Infectious Diseases Hospital, HIV/AIDS Department, Belgrade, Serbia.
Djordje
D
Jevtovic
Department of Infectious Diseases, Third Faculty of Medicine, Charles University Prague, Prague, Czech Republic.
Ladislav
L
Machala
Medical University of Innsbruck, Department of Dermatology and Venereal Diseases, Innsbruck, Austria.
Robert
R
Zangerle
Department of Infection and Population Health, University College London, London, United Kingdom.
Amanda
A
Mocroft
Department of Medicine I, Infectious Diseases Unit, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Jan
J
Van Lunzen
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D005060:Europe; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D054884:Host-Pathogen Interactions / Q000187:drug effects / Q000276:immunology; D006801:Humans; D053208:Kaplan-Meier Estimate; D007676:Kidney Failure, Chronic / Q000150:complications; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009369:Neoplasms / Q000150:complications; D017063:Outcome Assessment, Health Care / Q000379:methods / Q000706:statistics & numerical data; D011446:Prospective Studies; D012044:Regression Analysis; D012307:Risk Factors; D019562:Viral Load / Q000187:drug effects / Q000276:immunology; D055815:Young Adult
D044966:Anti-Retroviral Agents