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Low ART Adherence Is Associated With Higher Inflammation Despite HIV Suppression
Jose R. Castillo-Mancilla1; Todd T. Brown2; Kristine M. Erlandson1; Frank J. Palella3; Edward M. Gardner4; Bernard J. Macatangay5; Elizabeth Breen6; Lisa Jacobson2; Peter L. Anderson1; Nikolas I. Wada2
1Univ of Colorado, Denver, CO, USA;2Johns Hopkins Univ, Baltimore, MD, USA;3Northwestern Univ, Chicago, IL, USA;4Denver Hlth Med Cntr, Denver, CO, USA;5Univ of Pittsburgh Sch of Med, Pittsburgh, PA, USA;6Univ of California Los Angeles, Los Angeles, CA, USA
A significant proportion of virologically-suppressed HIV-infected individuals on antiretroviral therapy (ART) exhibit residual inflammation. It is unclear whether variable ART adherence, which could result in intermittent viral replication, partially explains this phenomenon. We aimed to determine if suboptimal ART adherence is associated with increased inflammation despite HIV suppression.
Longitudinal adherence data (4-day self-report) and serum concentrations of 24 biomarkers of inflammation and immune activation were measured at the same study visit in virologically-suppressed (<50 copies/ml) HIV-infected men in the Multicenter AIDS Cohort Study (MACS) from 1998 to 2009. We used generalized gamma regression to estimate the effect of <100% ART adherence on the concentrations of these biomarkers. We also categorized adherence using the clinically meaningful cutoffs of <85%, 85-99%, and 100%. Data are presented as percentage differences in biomarker concentrations across groups; we adjusted for multiple testing by controlling the false discovery rate at 5% using the Benjamini-Hochberg procedure.
We studied 927 men (225 African American; 143 Hispanic) for a total of 2901 person-visits at which HIV viral suppression was documented. Median (range) age was 48 (21-81) years. ART included PI-based (50%), NNRTI-based (46%) and NRTI-only (3%) regimens. Models were adjusted for covariates associated with both adherence and biomarker concentrations in univariate analyses: age, race, HCV co-infection, and depression. Individuals reporting <100% adherence had higher concentrations of pro-inflammatory cytokines and C-reactive protein compared to men reporting 100% adherence (Table, shaded column). Differences were significant at p<0.05 for six biomarkers, but only for TNF-α and IFN-γ after adjusting for multiple tests. Further evaluation of adherence sub-categories showed that, after controlling for multiple testing, significantly higher concentrations of four biomarkers were identified in individuals reporting <85% adherence (Table).
Suboptimal self-reported adherence was associated with higher concentrations of inflammatory biomarkers in virally-suppressed HIV-infected men. This suggests that adherence variations could have significant biological consequences beyond plasma HIV RNA suppression, possibly due to residual viral replication (i.e., below the limit of detection). Maximizing ART adherence could improve chronic inflammation and its deleterious long-term consequences.