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 HIV and Coverage of the
th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2009)
September 12-15, 2009, San Francisco, CA
 The material posted on HIV and about the 49th ICAAC is not approved by the American Society for Microbiology
Does Endothelial Function Decline after Starting Antiretroviral Therapy?

Endothelial function, or ability of blood vessels to expand normally, may be impaired in HIV patients who start antiretroviral therapy (ART), according to a small study presented last month at the 49th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2009) in San Francisco. This may help explain the increased risk of cardiovascular problems seem in some studies.

By Liz Highleyman

Since the advent of effective combination ART in the mid-1990s, several studies have observed an elevated rate of heart attacks and other cardiovascular events in people with HIV. Some studies have linked heart risk to specific antiretroviral drugs or drug classes -- including protease inhibitors and the nucleoside reverse transcriptase abacavir (Ziagen, also in the Epzicom and Trizivir coformulations) -- but data are not consistent, and some have found an elevated risk in HIV positive people who are not on treatment.

In the present study, Danish researchers investigated whether peripheral endothelial vasomotor function (ability of blood vessels to dilate and contract) changed when treatment-naive HIV patients started ART.

This prospective longitudinal analysis included 9 previously untreated participants. All were men and the median age was 51 years. Median duration of HIV infection was about 2 years and the mean baseline CD4 count was 260 cells/mm3. After 6 months on their first ART regimen, all achieved complete viral suppression and the mean CD4 count increased to 402 cells/mm3.

Most of the participants (7 of 9) started a regimen of efavirenz plus tenofovir/emtricitabine (the drugs in the Atripla coformulation), with 1 starting abacavir/lamivudine (the drugs in the Epzicom coformulation) and 1 starting zidovudine/lamivudine (the drugs in the Combivir coformulation).

Vasomotor function was assessed by measuring flow-mediated dilation (FMD) and nitroglycerin-mediated dilation (NMD) of the brachial artery in the upper arm using high-resolution Doppler ultrasound. FMD refers to how well blood vessels respond to changes in blood flow; nitroglycerin is a drug used to expand blood vessels. Study participants were examined before and 1 month after ART initiation. Brachial artery scans were recorded at rest and during increased blood flow caused by inflating and deflating a cuff (as done when measuring blood pressure, but for a longer period of 4.5 minutes).


1 month after ART initiation, flow-mediated dilation decreased significantly, from 8.7% to 4.6% (P = 0.027).
FMD remained impaired at the end of the 6 month follow-up period (5.1%; P = 0.064).
Nitroglycerin-mediated dilation increased slightly, but the change did not reach statistical significance (12.8% vs 14.3% at 1 month; P = 0.21).
Blood lipid levels were not significantly different at 6 months compared with baseline.

These findings led the investigators to conclude that, "FMD decreases 1 month after initiation of ART in treatment-naive HIV patients."

"This indicates that ART initiation leads to endothelial dysfunction, which could be a mechanism involved in the increased risk of cardiovascular disease found in recent observational studies," they continued.

Another recent study indicated that patients taking abacavir had a greater decrease in FMD, but HIV patients on ART overall had below normal levels. Further study is needed to determine the mechanism by which antiretroviral drugs might cause endothelial dysfunction, as well as the role of chronic inflammation due to HIV infection itself.

Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; University of Copenhagen, Copenhagen, Denmark; Hvidovre University Hospital, Denmark; Frederiksberg University Hospital, Denmark.


US Kristoffersen, A-M Lebech, N Wiinberg, and others. Peripheral Endothelial Function is Reduced after Initiation of Antiretroviral Therapy in Treatment Naïve HIV Patients: A Prospective Longitudinal Study. 49th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2009). San Francisco. September 12-15, 2009. Abstract H-1579.

























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