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Associations between immune depression and cardiovascular events in HIV infection
Caroline A Sabin1, Lene Ryom, Stephane De Wit
1aResearch Department of Infection and Population Health, UCL, London, UK bCopenhagen HIV Programme, University of Copenhagen, Copenhagen, Denmark cDepartment of Infectious Diseases, CHU Saint-Pierre Hospital, Brussels, Belgium dDivision of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland eHospital San Paolo, University of Milan, Milan, Italy fAcademic Medical Center, and Stichting HIV Monitoring, Amsterdam, The Netherlands gICAP-Columbia University/Harlem Hospital, New York, USA hDépartement de Santé Publique, Centre Hospitalier Universitaire, Nice iINSERM, Centre INSERM U897 'Epidémiologie et Biostatistique' jUniversité Bordeaux Segalen, Institut de Santé Publique Epidémiologie Développement (ISPED), Bordeaux, France kKirby Institute, University of New South Wales, Sydney, Australia lEpidemiklinikken M5132, Copenhagen University Hospital/Rigshospitalet, Copenhagen, Denmark. *See Acknowledgements section for full listing of study group.
Insights
Low CD4 cell counts in HIV-positive individuals were not strongly linked to myocardial infarction or coronary heart disease. However, stroke rates were higher with lower CD4 counts, potentially due to misclassification.
Area of Science:
- Immunology
- Cardiovascular Medicine
- Infectious Diseases
Background:
- Human Immunodeficiency Virus (HIV) infection is associated with increased cardiovascular disease (CVD) risk.
- CD4 cell count is a key indicator of immune status in HIV-positive individuals.
- Understanding the relationship between immune depression and CVD events is crucial for patient management.
Purpose of the Study:
- To investigate the association between CD4 cell counts (latest/nadir) and duration of immune depression with myocardial infarction (MI), coronary heart disease (CHD), stroke, and cardiovascular disease (CVD) in a large cohort of HIV-positive individuals.
- To determine if low CD4 cell counts increase the risk of specific cardiovascular events in the HIV-positive population.
Main Methods:
- A longitudinal cohort study involving 33,301 HIV-positive individuals.
- Poisson regression analysis was used to assess the associations.
- Stroke endpoint analysis was robustly evaluated by including stroke-like events and rejected strokes.
Main Results:
- No significant association was found between lower latest/nadir CD4 cell counts and increased risk of MI or CHD.
- Higher rates of stroke and CVD were observed in individuals with a latest CD4 cell count below 100 cells/μl.
- While all events were less frequent in individuals without immune depression, the association with the duration of immune depression was weak.
Conclusions:
- There is no strong evidence linking low CD4 cell counts to a higher likelihood of MI or CHD in HIV-positive individuals.
- Strokes appear more common at low CD4 cell counts, but this association may be influenced by misclassification or other biases.
- Further research is needed to clarify the relationship between immune status and stroke risk in the context of HIV infection.
Objective:
To consider associations between the latest/nadir CD4 cell count, and time spent with CD4 cell count less than 200 cells/μl (duration of immune depression), and myocardial infarction (MI), coronary heart disease (CHD), stroke, or cardiovascular disease (CVD) (CHD or stroke) in 33 301 HIV-positive individuals.
Design:
Longitudinal cohort study.
Methods:
Analyses were undertaken using Poisson regression. To investigate whether analyses of stroke were robust to the type of endpoint, we additionally included stroke-like events and rejected strokes into the stroke endpoint.
Results:
Participants experienced 716 MI, 1056 CHD, 303 stroke, and 1284 CVD events. Whereas there was no evidence of a higher MI/CHD risk in those with lower latest/nadir CD4 cell counts after adjustment [current CD4 <100 cells/μl: relative rate (95% confidence interval) 0.96 (0.62-1.50) for MI, 0.89 (0.30-2.36) for CHD; nadir CD4 <100 cells/μl: 1.36 (0.57-3.23) for MI, 0.98 (0.45-2.16) for CHD], stroke and CVD rates were higher in those with a latest CD4 cell count less than 100 cells/μl [2.26 (1.29-3.94) and 1.14 (0.84-1.56), respectively]. All events occurred less frequently in those who had not experienced immune depression, although evidence for a linear association with duration of immune depression was weak. The association between stroke risk and the latest CD4 cell count strengthened as stroke-like and rejected strokes were included; conversely, associations with established stroke risk factors weakened.
Conclusion:
We do not find strong evidence that HIV-positive individuals with a low CD4 cell count are more likely to experience MI/CHD. Although strokes appear to occur more commonly at low CD4 cell counts, this may be partly explained by misclassification or other biases.
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