Interruption of antiretroviral therapy and risk of cardiovascular disease in persons with HIV-1 infection: exploratory analyses from the SMART trial

Antivir Ther. 2008;13(2):177-87.


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: NCT00027352.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / administration & dosage*
  • Anti-HIV Agents / therapeutic use
  • Cardiovascular Diseases / complications
  • Cardiovascular Diseases / epidemiology*
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • HIV Infections / complications*
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • HIV-1 / drug effects*
  • HIV-1 / physiology
  • Humans
  • Male
  • Middle Aged
  • Reverse Transcriptase Inhibitors / administration & dosage*
  • Reverse Transcriptase Inhibitors / therapeutic use
  • Risk Factors
  • Treatment Outcome
  • Viral Load


  • Anti-HIV Agents
  • Reverse Transcriptase Inhibitors

Associated data