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  49th ICAAC
San Francisco, CA
September 12-15, 2009
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Endothelial Function Drops in First Month of Antiretroviral Therapy
  49th ICAAC (Interscience Conference on Antimicrobial Agents and Chemotherapy), September 12-15, 2009, San Francisco
Mark Mascolini
Endothelial function, measured as flow-mediated dilation in 9 people, declined significantly in the first month of therapy and remained low through 6 months of follow-up [1]. Researchers from Copenhagen University Hospital and other centers in Denmark suggest their findings mean that starting antiretrovirals--in all these cases, an efavirenz regimen--"leads to endothelial dysfunction which could be a mechanism involved in the increased risk of cardiovascular disease" in people with HIV.
These findings are at odds with other recent research [2,3], but support other work [4]. Endothelial function is both a central mechanism of atherosclerosis and a marker of cardiovascular risk.
The Danish study involved 9 men starting their first antiretrovirals, efavirenz with tenofovir/emtricitabine in 7, with abacavir/lamivudine in 1, and with zidovudine/lamivudine in 1. The investigators measured flow-mediated dilation and nitroglycerin-mediated dilation of the brachial artery by high-resolution Doppler ultrasound before treatment began and after 1 and 6 months of therapy.
The study group had a median age of 51 (range 35 to 60), an average body mass index of 22.2 kg/m(2), and an average blood pressure of 108/61 mm Hg (14/11 standard deviation). Pretreatment CD4 counts averaged 260 (range 180 to 350) and viral load 48,459 copies (range 6580 to 265,000). The men had been infected for a median of 25 months (range 2 to 176). After 6 months of treatment, everyone had a viral load under 40 copies and the average CD4 count had climbed to 402 (range 210 to 660).
Nitroglycerin-mediated dilation did not change after 1 or 6 months of therapy. But flow-mediated dilation fell significantly from before treatment to month 1 of treatment and remained depressed (but no longer significantly) at 6 months:
· Pretreatment: 8.7 +/- 1.7%
· After 1 month of antiretrovirals: 4.6 +/- 0.9% (P = 0.027)
· After 6 months of antiretrovirals: 5.1 +/- 0.8% (P = 0.064)
Average total cholesterol rose from 145 to 164 mg/dL after 1 month of treatment, then declined to 153 mg/dL. Average "good" high-density lipoprotein (HDL) cholesterol jumped from 28 mg/dL before treatment to 33 mg/dL at month 1 (P = 0.012) and to 42 mg/dL at month 6. Average "bad" low-density lipoprotein cholesterol rose from 87 mg/dL before treatment to 95 mg/dL at months 1 and 6. Triglycerides climbed from an average 133 mg/dL before treatment to 215 mg/dL after 1 month of therapy, but then fell back to 80 mg/dL. The investigators did not explain whether antilipid therapy accounted for these swings.
A retrospective case-control study that relied on markers of soluble endothelial and platelet activation found that chronic infection--not treatment with nonnucleosides or protease inhibitors--induced alterations in markers of endothelial function [2]. This study involved 56 people with HIV infection starting antiretrovirals and 28 healthy controls.
Measurements of brachial artery flow-mediated dilation in ACTG 5152 participants found significant improvements in endothelial function after 4 and 24 weeks of therapy in 82 previously untreated people starting regimens without (1) nucleosides, (2) nonnucleosides, or (3) protease inhibitors [3]. In this study flow-mediated dilation rose from 3.68% before treatment by 0.74% at week 4 and by 2.74% at week 24.
In contrast, a study of 61 antiretroviral-treated people with an undetectable viral load gauged endothelial function by flow-mediated dilation of the brachial artery and found low flow-mediated dilation (3.5%), which was lower still in people taking abacavir (2.8%) [4].
1. Kristoffersen US, Lebech A, Wiinberg N, et al. Peripheral endothelial function is reduced after initiation of antiretroviral therapy in treatment naive HIV patients: a prospective longitudinal Study. 49th ICAAC (Interscience Conference on Antimicrobial Agents and Chemotherapy). September 12-15, 2009. San Francisco. Abstract H-1579.
2. Francisci D, Giannini S, Baldelli F, et al. HIV type 1 infection, and not short-term HAART, induces endothelial dysfunction. AIDS. 2009;23:589-596.
3. Torriani FJ, Komarow L, Parker RA, et al. Endothelial function in human immunodeficiency virus-infected antiretroviral-naive subjects before and after starting potent antiretroviral therapy: the ACTG (AIDS Clinical Trials Group) study 5152s. J Am Coll Cardiol. 2008;52:569-576.
4. Hsue PY, Hunt PW, Wu Y, et al. Association of abacavir and impaired endothelial function in treated and suppressed HIV-infected patients. AIDS. 2009;23:2021-2027.