September 15, 2010 (Boston, Massachusetts) — Specific risk factors for cardiovascular disease (CVD) were identified in HIV-infected but asymptomatic patients (i.e., long-term nonprogressors), according to a small study presented here at the 50th Interscience Conference on Antimicrobial Agents and Chemotherapy.
Untreated asymptomatic HIV-positive patients had thickened coronary arteries, elevated inflammatory markers, and low levels of high-density-lipoprotein (HDL) cholesterol, compared with control subjects. These findings in untreated patients suggest that the increased risk for CVD that has been documented in HIV-positive patients is related to the disease process itself and not to antiretroviral treatment.
"We found that HIV-accelerated atherosclerosis appears to be influenced by the virus itself, which induce changes such as we found," said Hector Bonilla, MD, assistant professor at Northeastern Ohio College of Medicine in Akron.
The cross-sectional case–control study involved 13 HIV-positive patients diagnosed at least 5 years previously who had stable CD4 cell counts, stable HIV-1 RNA viral loads, and no AIDS-defining illness, and who had not received antiretroviral therapy. These patients were compared with 13 healthy controls matched for age, race, and sex.
The mean time from HIV diagnosis was 13. 5 years. There were 9 males and 4 females in the HIV-positive group. Mean age was 44 years (range, 29 to 56 years). The most common risk factors for CVD in both groups were smoking (54% of HIV-positive patients and 77% of HIV-negative people) and dyslipidemia (15% and 8%, respectively).
Mean common carotid artery intima media thickness (CIMT), assessed by intravascular ultrasound, was similar between patients and control subjects, but a trend toward thickening in CIMT was observed at the bifurcation of the coronary artery (i.e, the bulb) in those who were HIV positive.
Looking at markers of inflammation, Dr. Bonilla reported that TNF-alfa was significantly elevated in HIV-positive patients, compared with control subjects (P = .002), and levels of concentration of soluble adhesion molecule (sVCAM-1), a marker of endothelial activation, trended higher in HIV-positive patients. C-reactive protein and adiponectin levels were normal in both groups.
Interestingly, Dr. Bonilla noted, low levels of HDL-cholesterol were seen in the HIV-positive group. In 8 of 13 patients, HDL-cholesterol was less than 40 mg/dL (mean, 32 mg/dL). No other differences in CVD risk factors were found between HIV-positive patients and control subjects.
"The factors identified in HIV-positive patients are all strongly correlated with atherosclerosis," Dr. Bonilla stated.
Jury Still Out on Cause and Effect
"It is not established whether the disease process itself or antiretroviral therapy leads to atherosclerosis and CVD. There are arguments in both directions," said Jens Lundgren, MD, from the University of Copenhagen HIV Programme in Denmark.
Large randomized trials are needed to address this problem in patients with HIV infection, Dr. Lundgren said, adding that the International Network for Strategic Initiatives in Global HIV Trial (INSIGHT) will do just that. This National Institute of Allergy and Infectious Diseases global network trial will include 4000 people with early HIV (CD4 count >500) and randomize them to either immediate antiretroviral therapy or delayed therapy until the CD4 count is around 350, he said.
"INSIGHT will clarify whether treatment has a positive effect on CVD. A substudy will assess arterial plasticity, which is a specific measure of whether untreated HIV will have an impact on the CVD process," he explained.
This is part of determining the risk/benefit ratio of providing treatment, Dr. Lundgren continued — specifically, whether treatment causes cardiovascular harm.
Dr. Bonilla and Dr. Lundgren have disclosed no relevant financial relationships.
50th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC): Abstract H-220. Presented September 12, 2010.
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Cite this: Accelerated Atherosclerosis in HIV-Positive Patients May be Due to Disease, Not Treatment - Medscape - Sep 15, 2010.