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Activation Marker Levels With Undetectable Viral Load Match Those of Uninfected People 4 Years Older
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20th International AIDS Conference, July 20-25, 2014, Melbourne
Mark Mascolini
HIV-positive people with an undetectable viral load have monocyte activation marker levels equivalent to those of HIV-negative people 2 to 4 years older, according to results of a 309-person Australian comparison [1]. HIV-positive people with uncontrolled viral replication have activation marker levels equivalent to those of HIV-negative people 9 to 13 years older.
Accumulating research shows high levels of inflammation and immune activation in people with HIV, even people with an undetectable viral load. Researchers from MelbourneÕs Burnet Institute and colleagues who conducted this study noted that uncontrolled inflammation contributes to several diseases prevalent in HIV populations, including heart and bone disease. Markers of inflammation and immune activation also rise with age in the healthy general population. This study aimed to compare inflammation and activation markers in two groups of people with HIV and a set of healthy individuals.
In plasma the investigators measured the immune activation markers sCD14, sCD163, neopterin, CXCL10, and lipopolysaccharide. In whole blood they analyzed monocyte subsets and phenotype by flow cytometry. The researchers used linear regression analysis adjusted for age and smoking status to assess associations between these biomarkers and age in people with controlled or uncontrolled HIV infection.
This cross-sectional study involved 309 people--52 with a detectable viral load, 88 with an undetectable load, and 169 healthy people without HIV. Median ages were 40 (range 19 to 63) in the viremic HIV group, 48 (20 to 70) in the virologically suppressed HIV group, and 48 (20 to 84) in healthy controls. About 80% of the HIV groups were men, compared with 67.5% of the HIV-negative group. Significantly higher proportions of viremic people (46%) and aviremic people (37.5%) smoked than did healthy controls (6.5%) (P < 0.001). The viremic and aviremic groups had median CD4 counts of 416 and 619 and median CD4 nadirs of 267 and 203.
Compared with the HIV-negative group, HIV-positive people with a detectable viral load had significantly higher levels of CXCL10, sCD14, sCD163, and neopterin (P < 0.001 for all), and three monocyte subsets. Compared with healthy controls, HIV-positive people with an undetectable viral load had significantly higher levels of the same four activation markers (P < 0.001 for all), but not monocyte subsets.
Levels of activation markers and monocyte subsets were significantly lower in HIV-positive people with an undetectable load than in those with uncontrolled viremia. Age-related increases in monocyte activation occurred at a similar rate in HIV-positive people with an undetectable viral load and in people without HIV.
Finally, the researchers used linear regression analysis adjusted for age and smoking status to determine the impact of HIV on age at which monocyte activation markers reach a certain level. People with a detectable viral load had activation marker levels the same as those in HIV-negative controls 9 to 13 years older (see list below). People with an undetectable viral load had activation marker levels the same as those in HIV-negative controls 2 to 4 years older (see list below).
Aging impact of viremic HIV on monocyte activation markers:
-- CXCL10: -12.0 years
-- sCD14: -9.0 years
-- sCD163: -11.6 years
-- Neopterin: - 12.9 years
-- Lipopolysaccharide: -9.7 years
Aging impact of aviremic HIV on monocyte activation markers:
-- CXCL10: -4.0 years
-- sCD14: -3.0 years
-- sCD163: -2.5 years
-- Neopterin: -1.8 years
-- Lipopolysaccharide: -3.8 years
The Australian investigators concluded that "HIV infection confers an increase in monocyte activation equivalent to up to 13 years of normal aging in viremic individuals and up to 4 years in virologically suppressed individuals."
Reference
1. Hearps A, Angelovich T, Maisa A, et al. Monocyte activation markers remain significantly elevated in virologically suppressed HIV+ individuals up to a level equivalent to an additional 5.5 years of healthy ageing. AIDS 2014. 20th International AIDS Conference. July 20-25, 2014. Melbourne. Abstract WEPE021.
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