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Higher levels of inflammatory markers found in elite controllers
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HIV elite controllers demonstrated higher levels of inflammatory markers despite low levels of viremia, according to data published in Open Forum Infectious Diseases.
“Recent reports have suggested that elite controllers may have a more inflammatory state and may be at greater risk of coronary atherosclerosis,” Jonathan Z. Li, MD, MMSc, assistant professor of medicine at Harvard Medical School and Brigham and Women’s Hospital, told Infectious Disease News. “We found that elite controllers do have higher levels of inflammation despite having low levels of HIV detected in the blood. More research is needed to determine if these patients may benefit from antiretroviral therapy.”
Jonathan Li
Li and colleagues identified 42 elite controllers from the International HIV Controllers Study. They measured inflammation levels in the elite controllers and compared them with those in two cohorts: 80 HIV-suppressed nonelite controllers and 43 HIV-negative individuals. Inflammation was characterized by the presence of 20 soluble markers of inflammation.
There were significant differences between the cohorts in the levels of 15 of the markers. Fourteen markers where highest among elite controllers, whereas RANTES was the only marker significantly higher among the other two cohorts. The levels of seven inflammatory markers — sCD14, IP-10, IL-4, IL-10, sCD40L, IFN-gamma and GM-CSF — were at least double in the elite controllers compared with either of the two cohorts. The levels of sCD14 and IL-4 were three times as high in elite controllers.
Using partial least squares discriminate analysis modeling, the researchers could differentiate between the cohorts and discern gender differences in inflammation markers. Lastly, the researchers found no association between inflammation markers and either residual viremia or CD4+ counts. Viral load was associated with CD4+ cell decline, but not inflammatory marker levels.
“The higher levels of inflammation found in elite controllers worries me, as some of these inflammatory markers have been linked to a higher risk of heart disease in other patient populations,” Li said. “There is a clinical trial of ART in elite controllers currently under way through the AIDS Clinical Trial Group. Hopefully, that study will provide additional details on the benefits of ART for these patients.” – by Emily Shafer
Jonathan Z. Li, MD, MMSc, can be reached at: jli22@partners.org.
Disclosure: Li reports no relevant financial disclosures.
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Joel Blankson, MD, PhD
This important study adds to findings from other recent studies that demonstrate that elite controllers have higher levels of inflammation and hospitalization than patients on ART. Perhaps it's not that surprising since studies have shown that these patients are in fact infected with replication-competent virus and that this virus replicates and evolves at low levels. It would be interesting to determine whether treatment with anti-inflammatory agents such as statins could downmodulate the inflammation in these patients without affecting the effective immune responses that control viral replication. I think studies that compare the results of anti-inflammatory agents to ART are needed, and that clinicians shouldn't conclude that elite controllers should be started on ART.
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