HIV positivity, protease inhibitor exposure and subclinical atherosclerosis: a systematic review and meta-analysis of observational studies.
BACKGROUND
Patients with HIV may have increased risk of atherosclerotic cardiovascular disease owing to multiple biological mechanisms.


OBJECTIVE
To evaluate the evidence for subclinical atherosclerosis among patients with HIV.


METHODS
Systematic review of observational studies.


METHODS
We searched Medline, Cochrane DSR, ACP Journal Club, DARE, CMR, HTA, NHSEED, Embase and the Cochrane Controlled Trials Register for studies published before November 2008.


METHODS
Eligible studies were cross-sectional, cohort, or case-control studies reporting carotid ultrasound intima-media thickness (CIMT), focal plaque incidence, or coronary artery calcium (CAC), as determined by HIV positivity or protease inhibitor (PI) exposure.


METHODS
Two independent reviewers abstracted data using a standardised form. The primary outcome was weighted mean difference (WMD) for 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 from six cross-sectional, seven case-control and 13 cohort studies were included, involving 5456 HIV positive and 3600 HIV negative patients.


RESULTS
The weighted mean CIMT was 0.04 mm thicker among patients with HIV than among non-HIV patients (95% CI 0.02 to 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 overestimation of the risk associated with HIV and PI exposure.
Hulten
E
E
Department of Cardiology, Walter Reed Army Medical Center, 6900 Georgia Ave NW, Washington DC 20307, USA. edward.hulten@amedd.army.mil
Mitchell
J
J
Scally
J
J
Gibbs
B
B
Villines
T C
TC
D000328:Adult; D002114:Calcinosis / Q000139:chemically induced / Q000473:pathology / Q000821:virology; D002340:Carotid Artery Diseases / Q000139:chemically induced / Q000473:pathology / Q000821:virology*; D003324:Coronary Artery Disease / Q000139:chemically induced / Q000473:pathology / Q000821:virology*; D004812:Epidemiologic Methods; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D008297:Male; D011480:Protease Inhibitors / Q000009:adverse effects*; D017539:Tunica Intima / Q000473:pathology
D011480:Protease Inhibitors