Associations between immune depression and cardiovascular events in HIV infection

Objective:To consider associations between the latest/nadir CD4(+) cell count, and time spent with CD4(+) cell count less than 200cells/l (duration of immune depression), and myocardial infarction (MI), coronary heart disease (CHD), stroke, or cardiovascular disease (CVD) (CHD or stroke) in 33301 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(+)<100cells/l: relative rate (95% confidence interval) 0.96 (0.62-1.50) for MI, 0.89 (0.30-2.36) for CHD; nadir CD4(+)<100cells/l: 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 100cells/l [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.