TY - JOUR
T1 - Suboptimal Adherence to Combination Antiretroviral Therapy Is Associated with Higher Levels of Inflammation despite HIV Suppression
AU - Castillo-Mancilla, Jose R.
AU - Brown, Todd T.
AU - Erlandson, Kristine M.
AU - Palella, Frank J.
AU - Gardner, Edward M.
AU - Macatangay, Bernard J.C.
AU - Breen, Elizabeth C.
AU - Jacobson, Lisa P.
AU - Anderson, Peter L.
AU - Wada, Nikolas I.
N1 - Funding Information:
Financial support. The MACS is funded primarily by NIAID, with additional cofunding from the National Cancer Institute, the National Institute on Drug Abuse (NIDA), and the National Institute of Mental Health (NIMH). Targeted supplemental funding for specific projects was also provided by the National Heart, Lung, and Blood Institute and the National Institute on Deafness and Communication Disorders. MACS data collection is also supported by the National Center for Advancing Translational Sciences, a component of the NIH (grant UL1-TR001079 to Johns Hopkins University Institute for Clinical and Translational Research), and the NIH Roadmap for Medical Research. The research was also supported by the HIV Prevention Trials Network, sponsored by the NIAID, the NIDA, the NIMH, and the Office of AIDS Research, NIH (grant UM1-AI068613) and by the NIAID (grants K23 AI104315 to J. R. C.-M. and K24 AI120834 to T. T. B.).
Funding Information:
Potential conflicts of interest. T. T. B. has served as a consultant for Gilead Sciences, Merck, Bristol-Myers Squibb, EMD-Serono, and Theratechnologies. K. M. E. has received research grant support from Gilead Sciences and has served as a consultant for Theratechnologies. F. J. P. has served as a speaker and consultant for Gilead Sciences, Janssen, Merck, and Bristol-Myers Squibb. L. P. J. has served as a consultant to Bristol-Myers Squibb. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
Publisher Copyright:
© 2016 Oxford University Press. All rights reserved.
PY - 2016/12/15
Y1 - 2016/12/15
N2 - Background. Human immunodeficiency virus (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 than 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 2, 6, and 10, interferon γ, tumor necrosis factor α, and C-reactive protein than person-visits at which 100% cART adherence (P < .05) was reported. These same differences were observed in person-visits reporting <85% versus 100% 4-day cART adherence, but not in visits reporting 85%–99% versus 100% cART adherence. After adjustment for multiple comparisons, tumor necrosis factor α remained significantly higher (11% increase; P < .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 than among more adherent men. Residual HIV replication (ie, below the limit of detection), more likely among men with suboptimal adherence, is a plausible mechanism. Whether improving cART adherence could affect residual inflammation and associated morbidity and mortality rates should be investigated.
AB - Background. Human immunodeficiency virus (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 than 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 2, 6, and 10, interferon γ, tumor necrosis factor α, and C-reactive protein than person-visits at which 100% cART adherence (P < .05) was reported. These same differences were observed in person-visits reporting <85% versus 100% 4-day cART adherence, but not in visits reporting 85%–99% versus 100% cART adherence. After adjustment for multiple comparisons, tumor necrosis factor α remained significantly higher (11% increase; P < .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 than among more adherent men. Residual HIV replication (ie, below the limit of detection), more likely among men with suboptimal adherence, is a plausible mechanism. Whether improving cART adherence could affect residual inflammation and associated morbidity and mortality rates should be investigated.
KW - adherence
KW - antiretroviral therapy
KW - inflammation
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U2 - 10.1093/cid/ciw650
DO - 10.1093/cid/ciw650
M3 - Article
C2 - 27660234
AN - SCOPUS:85037844195
SN - 1058-4838
VL - 63
SP - 1661
EP - 1667
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 12
ER -