Suboptimal adherence to ART was associated with higher levels of inflammation and immune activation in patients with HIV even if the virus was suppressed, according to an analysis of data from the Multicenter AIDS Cohort Study.
“These associations remained significant after adjusting for various potential confounding factors that can be associated with increased inflammation and, for [tumor necrosis factor-alpha (TNF-alpha)], even after adjusting for multiple comparisons,” Jose R. Castillo-Mancilla, MD, associate professor of medicine at the University of Colorado School of Medicine, and colleagues wrote in Clinical Infectious Diseases. “In addition, these findings were unchanged after controlling for statin use, which can exert an anti-inflammatory effect, and after restricting the analysis to persistently HIV RNA-suppressed individuals.”
The viral suppression made possible by ART has been associated with reductions in systemic inflammation among individuals infected with HIV, but it does not reduce it to the levels observed in people uninfected by HIV, the researchers said. Persistent inflammation and immune activation has been associated with the development of non-AIDS adverse events, including cardiovascular disease, end-stage renal disease, cognitive decline, frailty and cancer. However, the mechanisms by which non-AIDS adverse events develop are not well-understood. Therefore, Castillo-Mancilla and colleagues sought to determine the extent to which ART adherence is associated with greater levels of inflammation and immune activation.
They evaluated self-reported ART adherence data and serum concentrations of 24 biomarkers of inflammation and immune activation in 912 men with HIV and documented viral suppression (HIV RNA < 50 copies/mL) who contributed more than 2,816 person-visits from 1998 to 2009.
At each visit, men were asked about the number of pills they had taken during the past 4 days for each medication in their ART regimen and whether that usage was typical of their use over the past 6 months. Their answers were correlated with the specific biomarker concentrations.
In adjusted models, higher concentrations of interleukin (IL)-2, IL-6, IL-10, interferon-gamma, TNF-alpha and C-reactive protein were found for person-visits when less than 100% 6-month ART adherence was reported compared with person-visits when 100% ART adherence was reported (P < .05). The same differences were observed between person-visits reporting less than 85% 4-day ART adherence compared with 100% 4-day ART adherence.
Person-visits reporting 85% to 99% 4-day ART adherence compared with 100% ART adherence were not significantly associated with higher concentrations of any biomarker, excluding TNF-alpha. After adjusting for multiple comparisons, higher concentrations of TNF-alpha (11%; P < .001) were associated with adherence that was less than 100%.
Castillo-Mancilla and colleagues noted that increases in biomarker inflammation persisted after the analysis was limited to patients with long-term HIV suppression.
“This suggests that the negative effects of suboptimal adherence on residual inflammation and immune activation include a patient population generally presumed to have the highest level of [ART] adherence,” they wrote. “[It] supports the premise that incomplete adherence, although sufficient to achieve and sustain viral suppression by conventional assays, may have significant detrimental consequences not previously identified.” – by Sarah Kennedy
Disclosure: Castillo-Mancilla reports no relevant financial disclosures. Please see the full study for a list of all other authors’ relevant financial disclosures.