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Initiation of antiretroviral therapy in early HIV infection reduces but does not abrogate chronic residual inflammation

  1. Author:
    Sereti, I.
    Krebs, S. J.
    Phanuphak, N.
    Fletcher, J. L.
    Slike, B.
    Pinyakorn, S.
    O'Connell, R. J.
    Rupert, Adam
    Chomont, N.
    Valcour, V.
    Kim, J. H.
    Robb, M. L.
    Michael, N. L.
    Douek, D. C.
    Ananworanich, J.
    Utay, N. S.

  2. Author Address

    Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. The Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA United States Military HIV Research Program; Walter Reed Army Institute of Research, Silver Spring, MD, USA. SEARCH, The Thai Red Cross AIDS Research Center, Bangkok, Thailand. The Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA United States Military HIV Research Program; Walter Reed Army Institute of Research, Silver Spring, MD, USA Armed Forces Research Institute of Medical Sciences, United States Army Medical Component, Department of Retrovirology, Bangkok, Thailand. AIDS Monitoring Laboratory, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc, Frederick, MD, USA. Centre de Recherche du CHUM and Department of Microbiology, Infectiology and Immunology, Universite de Montreal, Montreal, QC, Canada. University of California San Francisco Memory and Aging Center, Department of Neurology, Sandler Neurosciences Center, San Francisco, CA, USA. The Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA United States Military HIV Research Program; Walter Reed Army Institute of Research, Silver Spring, MD, USA Present address: International Vaccine Institute, SNU Research Park, Seoul, Korea. Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. The Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA United States Military HIV Research Program; Walter Reed Army Institute of Research, Silver Spring, MD, USA SEARCH, The Thai Red Cross AIDS Research Center, Bangkok, Thailand. Department of Internal Medicine, Division of Infectious Diseases, University of Texas Medical Branch at Galveston, Galveston, TX, USA.
    1. Year: 2017
    2. Date: Jan 15
    3. Epub Date: 10/25/2016
  2. Journal: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
    1. 64
    2. 2
    3. Pages: 124-131
  4. Type of Article: Article
  5. ISSN: 1058-4838
  1. Abstract:

    BACKGROUND: Serious non-AIDS events cause substantial morbidity and mortality despite HIV suppression with antiretroviral therapy (ART). Biomarkers of inflammation, coagulation cascade activation, and fibrosis predict these end-organ events. We aimed to determine whether ART initiation during acute HIV infection would attenuate changes in these biomarker levels. METHODS: Plasma samples were obtained from participants starting ART during acute HIV infection, chronic HIV infection, and HIV-uninfected participants, from Bangkok, Thailand. Biomarkers of inflammation (C-reactive protein [CRP], interleukin 6 [IL-6], soluble IL-6 receptor [sIL-6R], soluble gp130 [sgp130], TNF), enterocyte turnover (intestinal fatty acid binding protein [I-FABP]), lipopolysaccharide-induced monocyte activation (soluble CD14 [sCD14]), coagulation cascade activation [D-dimer], and fibrosis (hyaluronic acid [HA]) were measured at baseline and through 96 weeks of ART. RESULTS: CRP, TNF, sIL-6R, I-FABP, sCD14, D-dimer, and HA levels were elevated in acute HIV infection. Early ART was associated with increased I-FABP levels but normalization of TNF, sIL-6R, and D-dimer levels. CRP, sCD14, and HA levels decreased during ART, but remained elevated compared to HIV-uninfected participants. Higher sCD14, CRP, and D-dimer levels were associated with higher peripheral blood mononuclear cell and gut integrated HIV DNA levels. Decreases in sCD14 and CRP levels correlated with increases in CD4 T-cell counts. CONCLUSIONS: ART initiated in early acute HIV infection was associated with normalization of the coagulation cascade and several systemic inflammatory biomarkers, but the acute phase response, enterocyte turnover, monocyte activation, and fibrosis biomarkers remained elevated. Additional interventions to attenuate inflammation may be needed to optimize clinical outcomes in people with HIV infection.

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  2. DOI: 10.1093/cid/ciw683
  3. PMID: 27737952
  4. PMCID: PMC5215214
  5. View record in Web of Science®
  6. WOS: 000397132300009

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