Cardiovascular and cerebrovascular events in patients treated for human immunodeficiency virus infection

N Engl J Med. 2003 Feb 20;348(8):702-10. doi: 10.1056/NEJMoa022048.


Background: Metabolic abnormalities associated with human immunodeficiency virus (HIV) infection, including dysglycemia and hyperlipidemia, are increasingly prevalent, and there is concern about the possibility of an association with accelerated cardiovascular and cerebrovascular disease.

Methods: We conducted a retrospective study of the risk of cardiovascular and cerebrovascular disease among the 36,766 patients who received care for HIV infection at Veterans Affairs facilities between January 1993 and June 2001.

Results: For antiretroviral therapy, 70.2 percent of the patients received nucleoside analogues, 41.6 percent received protease inhibitors, and 25.6 percent received nonnucleoside reverse-transcriptase inhibitors for a median of 17 months, 16 months, and 9 months, respectively. Approximately 1000 patients received combination therapy with a protease inhibitor for at least 48 months, and approximately 1000 patients received combination therapy with a nonnucleoside reverse-transcriptase inhibitor for at least 24 months. Between 1995 and 2001, the rate of admissions for cardiovascular or cerebrovascular disease decreased from 1.7 to 0.9 per 100 patient-years, and the rate of death from any cause decreased from 21.3 to 5.0 deaths per 100 patient-years. Patient-level regression analyses indicated that there was no relation between the use of nucleoside analogues, protease inhibitors, or nonnucleoside reverse-transcriptase inhibitors and the hazard of cardiovascular or cerebrovascular events, but the use of antiretroviral drugs was associated with a decreased hazard of death from any cause.

Conclusions: Use of newer therapies for HIV was associated with a large benefit in terms of mortality that was not diminished by any increase in the rate of cardiovascular or cerebrovascular events or related mortality. Fear of accelerated vascular disease need not compromise antiretroviral therapy over the short term. However, prolonged survival among HIV infected patients means that longer-term observation and analysis are required.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Anti-HIV Agents / adverse effects
  • Anti-HIV Agents / therapeutic use*
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / etiology*
  • Cerebrovascular Disorders / epidemiology
  • Cerebrovascular Disorders / etiology*
  • Drug Utilization / trends
  • Female
  • Follow-Up Studies
  • HIV Infections / complications
  • HIV Infections / drug therapy*
  • HIV Infections / mortality
  • HIV Protease Inhibitors / adverse effects
  • HIV Protease Inhibitors / therapeutic use
  • Humans
  • Male
  • Middle Aged
  • Regression Analysis
  • Retrospective Studies
  • Reverse Transcriptase Inhibitors / adverse effects
  • Reverse Transcriptase Inhibitors / therapeutic use


  • Anti-HIV Agents
  • HIV Protease Inhibitors
  • Reverse Transcriptase Inhibitors