Background: The SMART trial found a raised risk of cardiovascular disease (CVD) events in patients undergoing CD4+ T cell-count guided intermittent antiretroviral therapy (ART) compared with patients on continuous ART. Exploratory analyses were performed to better understand the reasons for this observation.
Methods: A total of 5,472 patients with CD4+ T-cell counts >350 cells/mm3 were recruited and randomized to either continuous ART (the viral suppression arm; VS) or CD4+ T-cell count-guided use of ART (the drug conservation arm; DC).
Results: Major CVD events developed in 79 patients. The hazard ratio (HR) for risk of CVD events for DC versus VS was 1.57 (95% confidence interval 1.00-2.46; P=0.05). There was no evidence that being off ART or a higher current HIV viral load were associated with increased CVD risk. Total cholesterol and low-density lipoprotein cholesterol were reduced as a result of ART interruption in DC patients but so was high-density lipoprotein (HDL) cholesterol, leading to a net unfavourable change in the total/HDL cholesterol ratio.
Conclusions: Reasons for the higher risk of CVD for DC compared with VS patients remain unclear. There was no clear evidence to suggest that ART interruption per se or a higher HIV viral load were associated with an increased CVD risk in the DC group. Lipid changes were less favourable among DC compared with VS patients, which could offer a partial explanation.
Trial registration: ClinicalTrials.gov NCT00027352.