Association of Suboptimal Antiretroviral Therapy Adherence With Inflammation in Virologically Suppressed Individuals Enrolled in the SMART Study

Jose R Castillo-Mancilla, Andrew N Phillips, James D Neaton, Jacqueline Neuhaus, Simon Collins, Sharon Mannheimer, Sarah Pett, Veronique Touzeau-Römer, Mark N Polizzotto, Jens D Lundgren, Edward M Gardner, INSIGHT SMART Study Group, Jose R Castillo-Mancilla, Andrew N Phillips, James D Neaton, Jacqueline Neuhaus, Simon Collins, Sharon Mannheimer, Sarah Pett, Veronique Touzeau-Römer, Mark N Polizzotto, Jens D Lundgren, Edward M Gardner, INSIGHT SMART Study Group

Abstract

Suboptimal (ie, <100%) antiretroviral therapy (ART) adherence has been associated with heightened inflammation in cohort studies, even among people with virologic suppression. We aimed to evaluate this association among participants in the Strategies for Management of Antiretroviral Therapy (SMART) study who had virologic suppression (HIV-1 VL < 200 copies/mL) at enrollment. Based on self-reported adherence (7-day recall), plasma concentrations of interleukin 6 and D-dimer were 9% (95% confidence interval [CI], 1%-18%; P = .02) and 11% (95% CI, 1%-22%; P = .03) higher in participants who reported suboptimal vs 100% adherence, respectively. These findings confirm previous observations and support the hypothesis that suboptimal ART adherence, even in the context of virologic suppression, may have significant biological consequences. ClinicalTrials.gov number NCT00027352.

Keywords: SMART study; adherence; antiretroviral therapy; inflammation.

References

    1. Neuhaus J, Jacobs DR Jr, Baker JV et al. . Markers of inflammation, coagulation, and renal function are elevated in adults with HIV infection. J Infect Dis 2010; 201:1788–95.
    1. Borges ÁH, Silverberg MJ, Wentworth D et al. ; INSIGHT SMART; ESPRIT; SILCAAT Study Groups. Predicting risk of cancer during HIV infection: the role of inflammatory and coagulation biomarkers. AIDS 2013; 27:1433–41.
    1. Borges ÁH, O’Connor JL, Phillips AN et al. ; INSIGHT SMART Study and ESPRIT Groups. Interleukin 6 is a stronger predictor of clinical events than high-sensitivity C-reactive protein or D-dimer during HIV infection. J Infect Dis 2016; 214:408–16.
    1. Castillo-Mancilla JR, Brown TT, Erlandson KM et al. . Suboptimal adherence to combination antiretroviral therapy is associated with higher levels of inflammation despite HIV suppression. Clin Infect Dis 2016; 63:1661–7.
    1. Castillo-Mancilla J, Morrow M, Boum Y et al. . Greater ART adherence is associated with less inflammation in HIV-suppressed Ugandans. Poster Presented at: CROI February 13–16 2017; Seattle, WA. Abstract 675.
    1. El-Sadr WM, Lundgren J, Neaton JD et al. ; Strategies for Management of Antiretroviral Therapy Study G. CD4+ count-guided interruption of antiretroviral treatment. N Engl J Med 2006; 355:2283–96.
    1. O’Connor JL, Gardner EM, Esser S et al. ; International Network for Strategic Initiatives in Global HIV Trials (INSIGHT) Strategies for Management of Antiretroviral Therapy (SMART) Study Group. A simple self-reported adherence tool as a predictor of viral rebound in people with viral suppression on antiretroviral therapy. HIV Med 2016; 17:124–32.
    1. Mannheimer S, Friedland G, Matts J et al. . The consistency of adherence to antiretroviral therapy predicts biologic outcomes for human immunodeficiency virus-infected persons in clinical trials. Clin Infect Dis 2002; 34:1115–21.
    1. Borges ÁH, O’Connor JL, Phillips AN et al. ; INSIGHT SMART and ESPRIT Study Groups and the SILCAAT Scientific Committee. Factors associated with plasma IL-6 levels during HIV infection. J Infect Dis 2015; 212:585–95.
    1. Kuller LH, Tracy R, Belloso W et al. ; INSIGHT SMART Study Group. Inflammatory and coagulation biomarkers and mortality in patients with HIV infection. PLoS Med 2008; 5:e203.
    1. Wada NI, Jacobson LP, Margolick JB et al. . The effect of HAART-induced HIV suppression on circulating markers of inflammation and immune activation. AIDS 2015; 29:463–71.
    1. McKibben RA, Margolick JB, Grinspoon S et al. . Elevated levels of monocyte activation markers are associated with subclinical atherosclerosis in men with and those without HIV infection. J Infect Dis 2015; 211:1219–28.
    1. Hunt PW, Lee SA, Siedner MJ. Immunologic biomarkers, morbidity, and mortality in treated HIV infection. J Infect Dis 2016; 214(Suppl 2):S44–50.
    1. Group BT. Weekends-off efavirenz-based antiretroviral therapy in HIV-infected children, adolescents, and young adults (BREATHER): a randomised, open-label, non-inferiority, phase 2/3 trial. Lancet HIV 2016; 3:e421–30.
    1. de Truchis P, Assoumou L, Landman R et al. . No increase in HIV-1 reservoir and inflammation markers in four days a week short-cycles maintenace therapy: the ANRS 162-4D trial. Poster Presented at: IAS 2017: 9th IAS Conference on HIV Pathogenesis Treatment and Prevention; July 23–26, 2017;Paris, France.
    1. Mavigner M, Delobel P, Cazabat M et al. . HIV-1 residual viremia correlates with persistent T-cell activation in poor immunological responders to combination antiretroviral therapy. PLoS One 2009; 4:e7658.
    1. Ostrowski SR, Katzenstein TL, Pedersen BK et al. . Residual viraemia in HIV-1-infected patients with plasma viral load <or=20 copies/ml is associated with increased blood levels of soluble immune activation markers. Scand J Immunol 2008; 68:652–60.
    1. Lorenzo-Redondo R, Fryer HR, Bedford T et al. . Persistent HIV-1 replication maintains the tissue reservoir during therapy. Nature 2016; 530:51–6.
    1. Pearson CR, Simoni JM, Hoff P et al. . Assessing antiretroviral adherence via electronic drug monitoring and self-report: an examination of key methodological issues. AIDS Behav 2007; 11:161–73.
    1. Hileman CO, Kinley B, Scharen-Guivel V et al. . Differential reduction in monocyte activation and vascular inflammation with integrase inhibitor-based initial antiretroviral therapy among HIV-infected individuals. J Infect Dis 2015; 212:345–54.

Source: PubMed

Patrocinadores y Colaboradores

Condiciones médicas

Intervenciones de drogas

3
Suscribir