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

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

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.

Publication types

  • Multicenter Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acquired Immunodeficiency Syndrome / drug therapy*
  • Acquired Immunodeficiency Syndrome / immunology
  • Acquired Immunodeficiency Syndrome / virology
  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Retroviral Agents / therapeutic use*
  • CD4 Lymphocyte Count
  • Europe
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / immunology
  • HIV Infections / virology
  • HIV-1 / drug effects*
  • HIV-1 / physiology
  • Host-Pathogen Interactions / drug effects
  • Host-Pathogen Interactions / immunology
  • Humans
  • Kaplan-Meier Estimate
  • Kidney Failure, Chronic / complications
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasms / complications
  • Outcome Assessment, Health Care / methods
  • Outcome Assessment, Health Care / statistics & numerical data
  • Prospective Studies
  • Regression Analysis
  • Risk Factors
  • Viral Load / drug effects
  • Viral Load / immunology
  • Young Adult

Substances

  • Anti-Retroviral Agents

Grants and funding

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. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.