Late Antiretroviral Therapy Raises Risk of Early Atherosclerosis

		SUMMARY: Starting antiretroviral therapy (ART) early, before CD4 cell count falls below 350 cells/mm3, may reduce the risk of stiffening of the arteries, an early sign of atherosclerosis that can lead to heart attacks, according to a University of California at San Francisco (UCSF) study described in the June 9, 2010 advance online edition of AIDS.

By Liz Highleyman

Large observational studies have found that people with HIV have a higher likelihood of cardiovascular disease and heart attacks compared with the general HIV negative population. The reason for this is not fully understood, but inflammation and metabolic changes related to antiretroviral drugs appear to play a role.

Jennifer Ho and colleagues from Steven Deeks' team at UCSF, which has done extensive work on HIV-related inflammation and its consequences, looked at whether earlier initiation of HIV treatment might reduce cardiovascular risk related to atherosclerosis. Findings were previously presented in part at the 17th Conference on Retroviruses and Opportunistic Infections (CROI) this past February.

As atherosclerosis progresses, arteries lose their elasticity, or ability to expand, as they become filled with plaques made up of lipids, immune cells, and other material. Eventually this blockage can impair blood flow, and pieces of plaque or blood clots can break away and become lodged in vessels supplying the heart (causing a heart attack) or the brain (causing a stroke).

The present analysis included 80 men, with a median age of 47 years, from the UCSF SCOPE cohort (who started ART during chronic infection) and the OPTIONS study (who started ART during acute infection, within 6 months after HIV exposure). About 80% had started therapy with a nadir (lowest-ever) CD4 T-cell count below 350 cells/mm3, the treatment guidelines threshold for ART initiation in effect at the time of the study.

All participants had undetectable viral load at the start of the study. The late starters had a lower nadir CD4 count (85 vs 494 cells/mm3) and current CD4 count (459 vs 785 cells/mm3) than the early starters. Traditional cardiovascular risk factors including smoking and high blood pressure were common.

Participants underwent non-invasive assessment of arterial stiffness using pulse wave analysis (to determine the augmentation index, normalized for a heart rate of 75 bpm) and carotid-femoral pulse wave velocity, 2 sensitive measures of cardiovascular risk.

The investigators used these data to determine the relationship between arterial stiffness and cardiovascular and HIV-related factors. The analysis was adjusted for cardiovascular risk factors including age, smoking, blood pressure, use of antihypertensive (high blood pressure) medication, diabetes, and elevated cholesterol.

Results

	In an unadjusted analysis, predictors of worse arterial stiffness included older age, high blood pressure, use of antihypertensive drugs, and nadir CD4 count below 350 cells/mm3 (all P < 0.05).
	After adjusting for cardiovascular risk and HIV-related factors, having a nadir CD4 count below 350 cells/mm3 was independently associated with greater arterial stiffness:
	7.3% increase in augmentation index (P = 0.003); 0.41 m/s increase in pulse wave velocity (P = 0.03).
	Neither duration of ART nor use of protease inhibitors, however, were associated with arterial stiffness.

Based on these findings, the investigators concluded, "Among treated HIV-infected individuals, arterial stiffness is independently associated with both traditional cardiovascular risk factors as well as a low nadir CD4 T-cell count."
"Our data suggest that cardiovascular risk among HIV-infected individuals could be reduced through early initiation of antiretroviral therapy, before CD4 T-cell counts are depressed, a concept that should be tested prospectively in future studies," they added.

Investigator affiliations: Division of Cardiology and Positive Health Program, San Francisco General Hospital, San Francisco, CA; Department of Epidemiology and Biostatistics, University of California at San Francisco, San Francisco, CA.

7/9/10

Reference
JE Ho, SG Deeks, FM Hecht, and others. Initiation of antiretroviral therapy at higher nadir CD4+ T-cell counts is associated with reduced arterial stiffness in HIV-infected individuals. AIDS (Abstract). June 9, 2010 (Epub ahead of print).