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 HIV and Hepatitis.com Coverage of the
17th Conference on Retroviruses and
Opportunistic
Infections (CROI 2010)
 February 16 - 19, San Franciso, California
Research Sheds New Light on HIV in the Gut

SUMMARY: Different forms of HIV genetic material are concentrated in different parts of the gastrointestinal tract, and HIV behavior and immune response appears different in the gut than in the blood, according to a poster presentation at the 17th Conference on Retroviruses & Opportunistic Infections (CROI 2010) this week in San Francisco.

By Liz Highleyman

From the earliest stages of infection, HIV causes injury to the lining of the intestines as it infects the many CD4 T-cells present. This damage can allow microbes residing in the gut to leak out. As these bacteria and their toxins such as lipopolysaccharide (LPS) enter the bloodstream a process known as microbial translocation they trigger systemic immune activation, and the resulting inflammatory response appears to contribute to a variety of non-AIDS conditions seen in people with HIV.

Steven Yukl and colleagues with the PLUS Study Group measured levels of HIV RNA, DNA, and T-cell activation throughout the gut and in peripheral blood mononuclear cells (immune cells such as lymphocytes, monocytes, and macrophages).

"The gut is a major reservoir for HIV persistence in patients receiving antiretroviral therapy (ART)," they hypothesized. "Distinct immune environments within the gut may support varying levels of HIV."

The study included 8 HIV positive patients on ART with a CD4 cell count > 200 cells/mm3 and plasma HIV RNA < 40 copies/mL for 3 to 12 years. The researchers obtained blood plasma, peripheral blood mononuclear cells, and endoscopic biopsies taken from the duodenum, terminal ileum, right colon, and rectum (different parts of the large and small intestine). T-cell subsets and activation markers (CD38, HLA-DR) were measured in peripheral cells and gut cells using flow cytometry.

Results

Low-level plasma HIV RNA was detectable in all patients using a highly sensitive assay (median 2.3 copies/mL).
Unspliced HIV RNA was detectable at each gut site in the majority of patients (63% to 88%) using real time PCR, but was undetectable using in situ hybridization.
HIV DNA levels increased from the duodenum (the first section of the small intestine) to the rectum (the last section of the large intestine).
HIV DNA per CD4 T-cell was higher at all 4 gut sites compared with peripheral blood mononuclear cells (ratios of 2.8 for duodenum, 6.5 for ileum, 6.3 for colon, and 9.1 for rectum).
The median unspliced HIV RNA (copies per CD4 cell) was also higher at all gut sites compared to peripheral blood mononuclear cells, peaking in the ileum (ratio 10.2).
HIV DNA correlated positively with T-cell activation markers in the peripheral blood mononuclear cells, but negatively with T-cell activation in the gut.
The ratio of unspliced HIV RNA to HIV DNA (transcriptional activity per infected cell) decreased from the small to the large intestine.
Multiply spliced RNA was detected infrequently in gut (0% to 16.7%) relative to peripheral blood mononuclear cells (50%).
RNA/DNA ratios were lower in the colon (median 0.01) and rectum (also 0.01) relative to peripheral blood mononuclear cells (median 0.06), reflecting "
paradoxically low HIV transcription given the higher level of T-cell activation in the gut.

"HIV DNA and RNA are both concentrated in the gut relative to blood, but HIV RNA is highest in the ileum whereas HIV DNA is highest in the rectum," the researchers concluded. "The inverse relationship between HIV DNA and T-cell activation in the gut and the paradoxically low levels of HIV expression in the large bowel suggest that different processes drive HIV persistence in the blood and gut."

San Francisco VAMC and University of California, San Francisco, CA; University Hospital Zurich, Switzerland; University of Minnesota, Minneapolis, MN; San Francisco General Hospital and University of California, San Francisco, CA.

2/26/10

Reference
S Yukl, S Gianella, Q Li, and others (PLUS Study Group). Differences in HIV Burden throughout the Gut of Patients on Suppressive ART: Implications for HIV Persistence. 17th Conference on Retroviruses & Opportunistic Infections (CROI 2010). San Francisco. February 16-19, 2010. Abstract 97.

 

 

 

 

 

 

 

 

 

 

 



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