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Despite Mucosal CD4+ T Cell Depletion, the Prevalence of GI Symptoms Is Low During Acute and Early HIV-1 Infection
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Reported by Jules Levin
DDW May 17-21, 2008, San Diego
Thomas C Lee1, Saurabh Mehandru2, Okebugwu Kamalu1,2, Lisa Malter1, Martin Markowitz2, Michael A Poles1,2
1. Medicine, Gastroenterology, New York University School of Medicine, New York, NY, USA, 2. Aaron Diamond AIDS Research Center, Rockefeller University, New York, NY, USA
Program abstract
Background: The gastrointestinal (GI) mucosa is a primary site of viral replication and CD4 depletion after HIV infection. The relationship between mucosal immune dysregulation and the development of GI symptomatology remains unclear. Having established that mucosal CD4 depletion occurs in all patients during acute/early HIV-1 infection, we asked if this correlated with the presence of GI symptoms.
In all, we studied 32 patients with acute/early HIV-1 infection and 38 controls including 24 patients with chronic HIV-1 infection and 14 HIV-uninfected subjects.
Methods: Rectosigmoid colonic mucosal tissue, obtained endoscopically, and peripheral blood were utilized to determine the percentage of CD4+ T cells and CD4:CD8 ratio in each site by flow cytometry. GI symptomatology, including diarrhea, nausea, and abdominal pain were noted at the time of endoscopic examination. Correlation was sought between the presence of GI symptomatology and virologic and immunologic parameters.
Results:
The acutely-infected subjects underwent endoscopy a mean of 38.5 days after their estimated date of HIV-1 infection, well after resolution of acute retroviral syndrome, while the patients with chronic infection were diagnosed with HIV-1 a mean of 7.3 years at the time of endoscopy.
Only 3 of 32 acutely-infected subjects and 2 of 24 chronically-infected subjects were receiving antiretroviral medications at the time of study.
Severe mucosal CD4+ T cell depletion was seen in both acute and chronic infection cohorts with mean mucosal CD4:CD8 ratios of 0.29 and 0.08 (HIV negative controls= 1.3).
Despite significant mucosal depletion in acute infection patients, diarrhea, abdominal pain and nausea were only seen in 6.25%, 0% and 6.25% of patients respectively.
In comparison, these symptoms were experienced by 62.5%, 37.5% and 33.3% of chronically-infected patients.
Factors associated with the development of diarrhea included the presence of chronic HIV-1 infection, and a past history of opportunistic infections.
While the degree of plasma viremia did not correlate with the presence of diarrhea, both mucosal and systemic CD4:CD8 ratios T cell did.
The presence of diarrhea was more highly correlated with the blood CD4:CD8 ratio, as compared to that of the mucosa.
Conclusions:
Despite severe mucosal CD4+ T cell depletion, GI symptomatology is rarely seen during the acute/early HIV-1 infection period after the acute retroviral syndrome.
However, a significant percentage of patients with chronic HIV-1 infection appear to develop GI symptoms. Development of GI symptoms correlates more strongly with the degree of systemic rather than GI mucosal immune depletion.
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