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Suboptimal cART Adherence is Associated with Higher Levels of Inflammation Despite HIV Suppression.

Suboptimal cART Adherence is Associated with Higher Levels of Inflammation Despite HIV Suppression.
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Castillo-Mancilla JR, Brown TT, Erlandson KM, Palella FJ, Gardner EM, Macatangay BJ, Breen EC, Jacobson LP, Anderson PL, Wada NI,


Castillo-Mancilla JR, Brown TT, Erlandson KM, Palella FJ, Gardner EM, Macatangay BJ, Breen EC, Jacobson LP, Anderson PL, Wada NI, (click to view)

Castillo-Mancilla JR, Brown TT, Erlandson KM, Palella FJ, Gardner EM, Macatangay BJ, Breen EC, Jacobson LP, Anderson PL, Wada NI,

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Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2016 9 22() pii

Abstract
BACKGROUND
 HIV-infected individuals exhibit residual inflammation regardless of virologic suppression. We evaluated whether suboptimal adherence to combination antiretroviral therapy (cART) is associated with greater residual inflammation compared to optimal adherence despite virologic suppression.

METHODS
 Longitudinal self-reported cART adherence data and serum concentrations of 24 biomarkers of inflammation and immune activation were measured at the same study visit in HIV RNA-suppressed (<50 copies/mL) HIV-infected men in the Multicenter AIDS Cohort Study from 1998 to 2009. Associations between dichotomized 6-month (<100% vs. 100%) and categorized 4-day (<85%, 85-99% and 100%) cART adherence with biomarker concentrations were evaluated. RESULTS
 A total of 912 men provided 2816 person-visits with documented plasma HIV RNA suppression. In adjusted models, person-visits at which <100% cART 6-month adherence was reported had higher concentrations of interleukin (IL)-2, IL-6, IL-10, interferon-γ, tumor necrosis factor-α (TNF-α) and C-reactive protein compared to person-visits at which 100% cART adherence (p<0.05) was reported. These same differences were observed in person-visits reporting <85% vs. 100% 4-day cART adherence, but not in visits reporting 85-99% vs. 100% cART adherence. After adjusting for multiple comparisons, TNF-α remained significantly higher (11%, p<0.001) in person-visits at which <100% adherence was reported. CONCLUSIONS
 Higher concentrations of inflammatory biomarkers were observed among HIV RNA-suppressed men who reported <100% cART adherence compared to more adherent men. Residual HIV replication (i.e, below the limit of detection), more likely among men with suboptimal adherence, is a plausible mechanism. Whether improving cART adherence could impact residual inflammation and associated morbidity and mortality should be investigated.

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