title: Suboptimal Adherence to Combination Antiretroviral Therapy Is Associated With Higher Levels of Inflammation Despite HIV Suppression.
abstract: 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.
authors.affiliation: Division of Infectious Diseases, School of Medicine.
authors.forename: Jose R
authors.initials: JR
authors.lastname: Castillo-Mancilla
authors.affiliation: Division of Endocrinology, Diabetes & Metabolism, Johns Hopkins University School of Medicine.
authors.forename: Todd T
authors.initials: TT
authors.lastname: Brown
authors.affiliation: Division of Infectious Diseases, School of Medicine.
authors.forename: Kristine M
authors.initials: KM
authors.lastname: Erlandson
authors.affiliation: Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Palella
authors.affiliation: Division of Infectious Diseases, School of Medicine.
authors.forename: Edward M
authors.initials: EM
authors.lastname: Gardner
authors.affiliation: Division of Infectious Diseases/HIV/AIDS Unit, University of Pittsburgh School of Medicine, Pennsylvania.
authors.forename: Bernard J C
authors.initials: BJ
authors.lastname: Macatangay
authors.affiliation: Department of Psychiatry & Biobehavioral Sciences, David Geffen School of Medicine at UCLA, University of California, Los Angeles.
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Breen
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Lisa P
authors.initials: LP
authors.lastname: Jacobson
authors.affiliation: Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Anderson
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Nikolas I
authors.initials: NI
authors.lastname: Wada
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D015415:Biomarkers; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000821:virology; D018451:Homosexuality, Male; D006801:Humans; D007249:Inflammation; D008137:Longitudinal Studies; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D057566:Self Report; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D015415:Biomarkers
keywords: adherence; antiretroviral therapy; inflammation