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Observational Study
. 2014 Jan 31;9(1):e87160.
doi: 10.1371/journal.pone.0087160. eCollection 2014.

Immuno-virological discordance and the risk of non-AIDS and AIDS events in a large observational cohort of HIV-patients in Europe

Alexander Zoufaly  1 , Alessandro Cozzi-Lepri  2 , Joanne Reekie  2 , Ole Kirk  3 , Jens Lundgren  3 , Peter Reiss  4 , Djordje Jevtovic  5 , Ladislav Machala  6 , Robert Zangerle  7 , Amanda Mocroft  2 , Jan Van Lunzen  1 ; EuroSIDA in EuroCoord
Collaborators, Affiliations
Observational Study

Immuno-virological discordance and the risk of non-AIDS and AIDS events in a large observational cohort of HIV-patients in Europe

Alexander Zoufaly et al. PLoS One. .

Abstract

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).

Conclusion: 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.

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Conflict of interest statement

Competing Interests: Primary support is provided by the European Commission BIOMED 1 (CT94-1637), BIOMED 2 (CT97-2713), the 5th Framework (QLK2-2000-00773), the 6th Framework (LSHP-CT-2006-018632), and the 7th Framework (FP7/2007–2013, EuroCoord no. 260694) programmes. Current support also includes unrestricted grants by Gilead, Pfizer, and Merck and Co. The participation of centres from Switzerland was supported by The Swiss National Science Foundation (Grant 108787). AZ received a grant from MSD SHARP & DOHME GmbH for the performance of this research. This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Figure 1
Figure 1. Flow chart showing selection of patients enrolled in EuroSIDA for the analysis.
Figure 2
Figure 2. Rates (and 95% confidence intervals) of fatal and non-fatal non-AIDS and AIDS in patients with and without immuno-virological discordance (ID).
See this image and copyright information in PMC

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