title: Initiation of antiretroviral therapy before detection of colonic infiltration by HIV reduces viral reservoirs, inflammation and immune activation.
abstract: Colonic infiltration by HIV occurs soon after infection, establishing a persistent viral reservoir and a barrier to cure. We investigated virologic and immunologic correlates of detectable colonic HIV RNA during acute HIV infection (AHI) and their response to antiretroviral treatment (ART).
  
  
  
  From 49,458 samples screened for HIV, 74 participants were enrolled during AHI and 41 consented to optional sigmoidoscopy, HIV RNA was categorized as detectable (≥50 copies/mg) or undetectable in homogenized colon biopsy specimens. Biomarkers and HIV burden in blood, colon and cerebrospinal fluid were compared between groups and after 24 weeks of ART.
  
  
  
  Colonic HIV RNA was detectable in 31 participants (76%) and was associated with longer duration since HIV exposure (median 16 vs. 11 days, p=0.02), higher median plasma levels of cytokines and inflammatory markers (CXCL10 476 vs. 148 pg/mL, p=0.02; TNF-RII 1036 vs. 649 pg/mL, p<0.01; neopterin 2405 vs. 1368 pg/mL, p=0.01) and higher levels of CD8+ T cell activation in the blood (human leukocyte antigen - antigen D related (HLA-DR)/CD38 expression 14.4% vs. 7.6%, p <0.01) and colon (8.9% vs. 4.5%, p=0.01). After 24 weeks of ART, participants with baseline detectable colonic HIV RNA demonstrated persistent elevations in total HIV DNA in colonic mucosal mononuclear cells (CMMCs) (median 61 vs. 0 copies/10(6) CMMCs, p=0.03) and a trend towards higher total HIV DNA in peripheral blood mononuclear cells (PBMC) (41 vs. 1.5 copies/10(6) PBMCs, p=0.06). There were no persistent differences in immune activation and inflammation.
  
  
  
  The presence of detectable colonic HIV RNA at the time of ART initiation during AHI is associated with higher levels of proviral DNA after 24 weeks of treatment. Seeding of HIV in the gut may have long-lasting effects on the size of persistent viral reservoirs and may represent an important therapeutic target in eradication strategies.
authors.affiliation: US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.|Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA; tcrowell@hivresearch.org.
authors.forename: Trevor A
authors.initials: TA
authors.lastname: Crowell
authors.affiliation: SEARCH, Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
authors.forename: James Lk
authors.initials: JL
authors.lastname: Fletcher
authors.affiliation: National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA.
authors.forename: Irini
authors.initials: I
authors.lastname: Sereti
authors.affiliation: US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.|Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
authors.forename: Suteeraporn
authors.initials: S
authors.lastname: Pinyakorn
authors.affiliation: Virus Isolation and Serological Lab, National Cancer Institute at Frederick, Frederick, MD, USA.
authors.forename: Robin
authors.initials: R
authors.lastname: Dewar
authors.affiliation: US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.|Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
authors.forename: Shelly J
authors.initials: SJ
authors.lastname: Krebs
authors.affiliation: SEARCH, Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
authors.forename: Nitiya
authors.initials: N
authors.lastname: Chomchey
authors.affiliation: Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Rungsun
authors.initials: R
authors.lastname: Rerknimitr
authors.affiliation: Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.|Department of Retrovirology, Armed Forces Research Institute of Medical Sciences - United States Component, Bangkok, Thailand.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Schuetz
authors.affiliation: US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
authors.forename: Nelson L
authors.initials: NL
authors.lastname: Michael
authors.affiliation: SEARCH, Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
authors.forename: Nittaya
authors.initials: N
authors.lastname: Phanuphak
authors.affiliation: Department of Microbiology, Infectiology and Immunology, Faculty of Medicine, Université de Montréal, Montréal, QC, Canada.|Centre de Recherche du CHUM, Montreal, QC, Canada.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Chomont
authors.affiliation: US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.|Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.|SEARCH, Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
authors.forename: Jintanat
authors.initials: J
authors.lastname: Ananworanich
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D015331:Cohort Studies; D003106:Colon / Q000821:virology*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D006801:Humans; D007249:Inflammation / Q000517:prevention & control; D007963:Leukocytes, Mononuclear; D008213:Lymphocyte Activation; D008297:Male; D012367:RNA, Viral; D013601:T-Lymphocytes / Q000276:immunology; D019562:Viral Load
chemical_list: D012367:RNA, Viral
keywords: CD4 lymphocyte count; HIV; highly active antiretroviral therapy; infectious disease reservoirs; inflammation; virus latency