You are here
HIV Burden and Biomarker Associations With Colonic HIV RNA During Acute HIV Infection
James L. Fletcher2, Trevor A. Crowell1, Robin Dewar3, Irini Sereti4, Bonnie Slike1, Nitiya Chomchey2, Rungsun Rerknimitr5, Nelson L. Michael1, Nicolas Chomont6, Jintanat Ananworanich1
1 US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, United States. 2 SEARCH, Thai Red Cross AIDS Research Centre, Bangkok, Thailand. 3 Virus Isolation and Serological Lab, National Cancer Institute at Frederick, Frederick, MD, United States. 4 National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, United States. 5 Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. 6 Vaccine and Gene Therapy Institute Florida, Port St. Lucie, FL, United States.
Background: The colonic mucosa is typically one of the first sites infiltrated during acute HIV infection (AHI), becoming an important reservoir for the virus and a barrier to cure. We investigated virologic and immunologic correlates of detectable colonic HIV RNA during AHI.
Methods: Subjects were prospectively enrolled and offered ART during AHI (Fiebig stages I-V) from May 2009 to March 2012 in Bangkok, Thailand. Sigmoidoscopy was performed to collect colon tissue. Subjects were categorized by detectable (≥50 copies/mg) or undetectable HIV RNA in colonic mucosal tissue cells using homogenized biopsy specimens and the Siemens Quantiplex HIV-1 3.0 assay. Biomarkers and HIV burden in multiple compartments were compared between groups using the Mann-Whitney U test.
Results: From 49,458 samples screened for HIV, 75 individuals were enrolled during AHI and 42 consented to optional colon biopsy and are included in this analysis. The median age was 29 and 93% were male. Colonic HIV RNA was detectable in 32 subjects (76%).
As compared to subjects without detectable colonic HIV RNA, those with detectable HIV RNA tended to be in a later Fiebig stage (19% Fiebig I in detectable group vs. 70% Fiebig I in undetectable group, p=0.04); had a longer reported duration since HIV exposure; had higher median levels of IP-10, TNF-RII and neopterin; and had higher expression of HLA-DR/CD38 and Ki-67 on CD8 cells in both blood and colon (Table 1). Median CD4 count in mucosal mononuclear cells was lower in volunteers with detectable colonic HIV RNA. Detectable colonic HIV RNA was also associated with higher HIV RNA levels in the peripheral blood and cerebrospinal fluid as well as higher levels of both total and integrated HIV DNA in both the peripheral blood and colon.
Among subjects with baseline detectable colonic HIV RNA, 23 of 26 tested (88%) were undetectable after 24 weeks of ART. The eight tested subjects who were undetectable at baseline remained undetectable.
Conclusions: This study highlights the rapidity and breadth of viral infiltration during AHI. Detectable colonic HIV RNA is common and correlates with increase HIV burden in the peripheral blood, colon, and CSF. Subjects with detectable colonic HIV RNA during AHI demonstrate colonic CD4 depletion, peripheral inflammation, and CD8+ T-cell activation in both colon and periphery. Subjects with undetectable colonic HIV RNA tended to be at earlier stages of AHI.