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ART in Acute Infection, Inflammation/Activation "Largely Disappear"
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HIV Burden and Biomarker Associations With Colonic HIV RNA During Acute HIV Infection
Reported by Jules Levin
CROI 2015 Feb 23-26, Seattle, WA
WEBCAST:http://www.croiwebcasts.org/console/player/25574?mediaType=slideVideo&
Trevor Crowell1, Bonnie Slike1, Nelson Michael1, Jintanat Ananworanich1, James Fletcher2, Nitiya Chomchey2, Robin Dewar3, Irini Sereti4, Rungsun Rerknimitr5, Nicolas Chomont6
2 SEARCH, Thai Red Cross AIDS Research Centre, Bangkok, Thailand;1 US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States;3 Virus Isolation and Serological Lab, National Cancer Institute at Frederick, Frederick, Maryland, United States;4 National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, United States;5 Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand;6 Vaccine and Gene Therapy Institute Florida, Port St. Lucie, Florida, United States
The colon is infiltrated during acute HIV infection; the colonic mucosa are enriched for the type of cells, CD4+ T-cell that are supportive for HIV infection & replication. Patients who start suppressive ART during chronic infection still demonstrate detectable HIV in the colonic mucosa in many cases. It is there important to understand correlates of colonic HIV RNA during AHI which so we can have a better understanding of HIV pathogenesis & inform our efforts at viral eradication.
Sigmoidoscopy was performed to collect colon tissue.
It is noteworthy that patients with detectable HIV in the colon tended to be at later stages in infection- Fiebig III/IV/V & to have been exposed to HIV longer & had higher colonic HIV RNA viral load.
RESULTS
After 24 weeks of suppressive ART started in AHI colonic HIV RNA decrease in both groups, the one with detectable colonic HIV-RNA & the the other with undetectable HIV-RNA. BUT there still remains a difference between those who started ART before or after there was detectable colonic HIV-RNA.
TOTAL HIV-DNA: COLON
When you look at HIV-DNA in the colon you see the same pattern. BUT the difference in total HIV -DNA in the colon persists after 24 weeks of ART for those who started therapy before HIV-RNA was detectable in the colon.
ART in AHI Reduced CD8 Activation in the Peripheral Viral Load & in the Colon
When you have detectable HIV RNA in the colon you tend to have a higher HIV RNA burden in the peripheral blood as well as in the CSF but in the anal lavarge you don't see a significant difference in HIV RNA burden in the peripheral blood whether HIV is detectable or not in the colon.
HIV-DNA IN PBMCs
When you have detectable HIV RNA in the colon you tend to have a higher proviral burden in the periphery measured by both total HIV DNA & Integrated HIV DNA
HIV-DNA in the Colonic Mucosa
Detectable HIV RNA in the colonic mucosa correlates with a higher burden of in the colonic mucosa as measured by both total & integrated HIV-DNA.
Plasma Cytokines & Inflammatory markers
Across the board you see a higher trend of higher markers of systemic inflammation when there is detectable colonic HIV-RNA.
CD4
We see CD4 depletion in the colon when HIV-RNA is detectable in the colon.
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