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Acute Retroviral Syndrome is Associated with Gut Mucosal CD4 Depletion, Inflammation and High Viral and Proviral Burden in Systemic and Tissue Compartments

Session: Oral Abstract Session: HIV Related Inflammation, Complications and Comorbidities
Friday, October 10, 2014: 10:30 AM
Room: The Pennsylvania Convention Center: 107-AB
Background: Most acute HIV infection (AHI) patients suffer acute retroviral syndrome (ARS), but information on virologic and immunologic correlates of ARS is limited.

Methods: Subjects were prospectively enrolled during AHI (Fiebig stages I-V) from May 2009 to February 2014 in Bangkok, Thailand. Study physicians completed a standardized checklist for each subject and those with ≥3 qualifying symptoms were considered to have ARS.  Colon tissue (n=42) and cerebrospinal fluid (CSF) (n=37) were collected on willing volunteers. HIV burden and biomarkers were compared between those with and without ARS using the Mann-Whitney U test.

Results: Of 97,920 persons screened for HIV infection, 150 were enrolled during AHI at a mean of 18.5 days since history of HIV exposure.  Median age was 28 years and 141 (94%) subjects were men. ARS was observed in 114 (76%). The most common symptoms were fever (94%), fatigue (81%), headache (72%), pharyngitis (60%), and myalgia (60%).

In blood, subjects with ARS had higher HIV RNA (median 5.7 vs. 4.6 log10copies/mL, p<0.001); total HIV DNA (134.1 vs. 7.5 copies/106 PBMCs, p=0.02); C-reactive protein (1431 vs. 644 µg/mL, p=0.004); tissue necrosis factor-α (7.41 vs. 4.71 pg/mL, p=0.001); and D-dimer (283 vs. 179 µg/mL, p=0.007).

In colon, subjects with ARS had lower absolute numbers of CD4+ T cells (6.60 vs. 11.8 x 106 cells/gm, p=0.02) and lower colonic HIV RNA (3.13 vs. 1.7 log10 copies/gm, p=0.009), while the frequency of activated CD8+ T cells (HLA-DR+/CD38+) was significantly increased (8.9% vs. 4.4%, p=0.01), as compared to subjects without ARS. In the CSF, ARS was associated with higher HIV RNA (3.7 vs. 1.8 log10 copies/mL, p=0.006) and neopterin (2482 vs. 1101 pg/mL, p=0.001). There were no correlations between these biomarkers and gastrointestinal or central nervous system symptoms.

Conclusion: Subjects with ARS had higher HIV RNA and proviral DNA in blood, colon and CSF. ARS was associated with depletion of CD4+ T cells and increased CD8 T cell activation in the sigmoid colon as well as heightened inflammation in the periphery. Patients with ARS may have poorer outcomes than those without ARS, particularly if they continue to display this unfavorable profile after treatment.

Trevor Crowell, MD1,2,3, James L.K. Fletcher, BMBCh4, Eugene Kroon, MD4,5, Suteeraporn Pinyakorn, MSc.4, Alexandra Schuetz, PhD3,5, Irini Sereti, MD, MHS6, Shelly J. Krebs, PhD2,3, Bonnie M. Slike, MSc2,3, Nicolas Chomont, PhD7, Linda L. Jagodzinski, PhD2,3, Netanya Sandler, MD8, Robin Dewar, Ph.D9, Rungsun Rerknimitr, MD10, Somprartthana Rattanamanee, RN, MSc4, Rapee Trichavaroj, MSc5, Victor G. Valcour, MD, PhD11, Serena Spudich, MD12, Merlin L. Robb, MD2,3, Jerome H. Kim, MD, FACP, FIDSA2, Nelson L. Michael, MD, PhD2, Nittaya Phanuphak, MD, PhD4, Jintanat Ananworanich, MD, PhD2,3,4 and the RV 254/SEARCH 010 Study Group, (1)Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD, (2)U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, (3)Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, (4)SEARCH, Thai Red Cross AIDS Research Centre, Bangkok, Thailand, (5)Department of Retrovirology, Armed Forces Research Institute of Medical Sciences United States Component, Bangkok, Thailand, (6)National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, (7)Vaccine and Gene Therapy Institute of Florida, Port St. Lucie, FL, (8)Division of Infectious Diseases, University of Texas Medical Branch, Galveston, TX, (9)Virus Isolation and Serological Lab, National Cancer Institute at Frederick, Frederick, MD, (10)Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand, (11)Department of Neurology, University of California San Francisco School of Medicine, San Francisco, CA, (12)Department of Neurology, Yale University School of Medicine, New Haven, CT


T. Crowell, None

J. L. K. Fletcher, None

E. Kroon, None

S. Pinyakorn, None

A. Schuetz, None

I. Sereti, None

S. J. Krebs, None

B. M. Slike, None

N. Chomont, None

L. L. Jagodzinski, None

N. Sandler, None

R. Dewar, None

R. Rerknimitr, None

S. Rattanamanee, None

R. Trichavaroj, None

V. G. Valcour, None

S. Spudich, None

M. L. Robb, None

J. H. Kim, None

N. L. Michael, None

N. Phanuphak, None

J. Ananworanich, None

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