Article Text

other Versions

Download PDFPDF
HIV positivity, protease inhibitor exposure, and subclinical atherosclerosis: A systematic review and meta-analysis of observational studies
  1. Edward Hulten (edward.hulten{at}
  1. Walter Reed Army Medical Center, United States
    1. Joshua Mitchell
    1. Walter Reed Army Medical Center, United States
      1. John Scally
      1. Walter Reed Army Medical Center, United States
        1. Barnett Gibbs
        1. Walter Reed Army Medical Center, United States
          1. Todd Villines
          1. Walter Reed Army Medical Center, United States


            Objective: To evaluate the evidence for subclinical atherosclerosis among HIV patients.

            Design: Systematic review of observational studies.

            Data sources: We searched Medline, Cochrane DSR, ACP Journal Club, DARE, CMR, HTA, NHSEED, EMBASE, and the Cochrane Controlled Trials Register for studies published prior to November 2008.

            Review methods: Eligible studies were cross-sectional, cohort, or case control studies reporting carotid ultrasound intima media thickness (CIMT), focal plaque incidence, or coronary calcium (CAC), as determined by HIV positivity or protease inhibitor (PI) exposure. Two independent reviewers abstracted data using a standardized form. The primary outcome was weighted mean difference (WMD) for carotid intima media thickness (CIMT) comparing HIV positive versus negative patients. Other outcomes included WMD by PI exposure and the odds ratio (OR) for a focal carotid plaque or CAC.

            Data synthesis: Data from six cross-sectional, seven case-control, and 13 cohort studies were included, involving 5,456 HIV positive and 3,600 HIV negative patients. The weighted mean CIMT was 0.04 mm thicker among HIV patients vs. non-HIV (95% CI, 0.02-0.06; p <0.001). HIV positivity was not associated with carotid plaque or CAC. PI exposure did not significantly affect CIMT, carotid plaque, or CAC. There was evidence of publication bias, and stratified analysis and meta-regression showed outcomes were influenced by study design, age, gender, and smoking. However, HIV positivity slightly increased CIMT even after sensitivity analyses.

            Conclusions: HIV infection and PI exposure are not strong independent risk factors for subclinical atherosclerosis. Confounding may contribute to over-estimation of the risk associated with HIV and PI exposure.

            Statistics from

            Request Permissions

            If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.