Clinical Topics

Army Researchers Identify a CV Bonus from Early ART Initiation in HIV

by Annette Boyle

July 22, 2019

SAN ANTONIO, TX—ART has never looked better, at least if you’re an individual recently diagnosed with human immunodeficiency virus. 

Researchers at the Brooke Army Medical Center in San Antonio recently determined that antiretroviral therapy reverses endothelial dysfunction, an unexpectedly common cardiovascular disease mechanism in young adults with recently diagnosed HIV.1

The effectiveness of ART in extending the expected lifespan of individuals with HIV to nearly that of their seronegative counterparts has made managing early contributors to cardiovascular disease ever more important. CVD now accounts for up to 22% of deaths among individuals with HIV, with risk rising with age.2

The destructive impact of HIV on vascular health appears to begin very early in the course of infection and affect patients who would not ordinarily be considered at high risk for cardiovascular issues, based on the work of the San Antonio team.

In a study presented at the Conference on Retroviruses and Opportunistic Infections in Seattle, the researchers determined that nearly one-quarter of newly diagnosed U.S. Air Force members had endothelial dysfunction as measured by reactive hyperemia index. RHI is a noninvasive measurement of peripheral arterial tonometry.

None of the airmen had other risk factors for cardiovascular disease.

Following initiation of ART, 3 out of 4 patients achieved normal endothelial function.

While the rate of endothelial dysfunction was higher than anticipated in a young cohort, the benefits of ART made sense to the researchers.

“Endothelial dysfunction is a pathological condition represented by an imbalance of endothelium relaxing and contracting factors. This imbalance coupled with a decrease in nitric oxide is described to be developed in response to numerous inflammatory and prothrombotic conditions,” explained co-author Kelvin N. V. Bush, MD, of the cardiology division of the Brooke Army Medical Center.

HIV infection promotes increased systemic inflammation and hypercoagulability, he noted, making endothelial dysfunction more likely.

A previous study found that HIV infection substantially increases the risk of premature atherosclerosis, independent of other cardiovascular risk factors, viral load, treatment or immunodeficiency.3

Endothelial dysfunction is a significant contributing factor to early atherosclerosis and appears to be driven by secretion of HIV proteins and cytokines into the endothelial microenvironment, which increases adhesiveness, permeability, cell death and oxidative stress.4

“Since effective ART results in viral suppression and reduces inflammation, this intervention is theorized to promote the reversal of endothelial dysfunction in our young population who was treated early before the onset of irreversible vascular damage,” co-author Jason F. Okulicz, MD, of Brooke’s infectious disease service, told U.S. Medicine.

High Rate of EDF

The researchers evaluated the response to ART among 61 airmen diagnosed with HIV between 2015 and 2017 who had RHI measurements recorded in their health records. Ninety-five percent of the patients were male. 

The researchers defined an abnormal RHI as a log-transformed reading of less than 0.51. All patients were advised to begin ART immediately.

Fourteen of the 61 Air Force members had abnormal readings that indicated endothelial dysfunction. The group with abnormal levels had a mean RHI of 0.30 vs. 0.82 among those with normal readings. 

The average age of individuals with and without abnormal RHI did not differ significantly, 27.8 vs. 27.5 years, nor did they have a longer interval from their last negative HIV test or time since estimated date of seroconversion. There were no significant differences in CD4 count or viral load.

Both groups had similar, low risk of cardiovascular disease based on common risk factors including BMI, tobacco use, cholesterol and hypertension prevalence. None of the patients had diabetes.

Patients in the group with abnormal readings were more likely to be white (50% vs. 28%) and less likely to be black (36% vs. 64%), but the differences were not found be significant. 

One factor emerged as particularly notable—age. Each decade above the mean doubled a patient’s odds of an abnormal RHI reading.

ART Restoration

A second RHI measurement was available for 41 patients, of which 40 started ART immediately after the first RHI assessment. Of those, 11 had abnormal RHI values initially. 

Following a median of 6.44 months of ART, “of the 11 patients who were abnormal at baseline and had a repeat RHI determination after starting ART, eight had normalized RHI,” Bush said.

“The remaining three patients did not normalize their RHI and maintained their values within the exam’s technical coefficient of variation. Two of the patients demonstrated interval adverse lipid profile changes with ART and this metabolic impact could have impaired reversible RHI changes,” he noted.

Overall, the 40 patients who began ART saw a mean rise of 0.33 in RHI.

What happened without treatment provided a lesson, too. “One patient declined ART and his RHI testing went from normal at baseline to abnormal at repeat testing,” Okulicz pointed out. After 8.3 months, this individual’s RHI declined from 0.60 to 0.11. 

The researchers concluded that “persistent EDF and subsequent CVD complications could be related to delayed ART” and noted that “further studies are needed to determine the role and timing of endothelial function testing in HIV-infected patients.”

1. Bush KNV, Teel JL, Alvarado GR, Watts JA, Gore RS, Okulicz JF. Endothelial dysfunction is common in early HIV infection and reversible with ART. Conference on Retroviruses and Opportunistic Infections (CROI). March 4-7, 2019. Seattle. Abstract 655.

2. Bedimo RJ, Westfall AO, Drechsler H, et al. Abacavir use and risk of acute myocardial infarction and cerebrovascular events in the highly active antiretroviral therapy era. Clin Infect Dis 2011;53:84-91.

3. Hsue PY, Hunt PW, Schnell A, Kalapus SC, Hoh R, Ganz P, et al. Role of viral replication, antiretroviral therapy, and immunodeficiency in HIV-associated atherosclerosis. AIDS. 2009;23:1059–67.

4. Anand AR, Rachel G, Parthasarathy D. HIV proteins and endothelial dysfunction: Implications in cardiovascular disease. Front Cardiovasc Med. 19 December 2018;5:185.



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