Gastrointestinal Symptoms Are Uncommon during Early HIV Infection, Despite CD4 Cell Depletion in the Gut

By Liz Highleyman

During the earliest stages of HIV infection, the virus actively replicates and kills CD4 T-cells in the mucosa (lining) of the gastrointestinal (GI) tract, or gut. However, the relationship between mucosal immune dysregulation and the development of GI symptoms is poorly understood.

In a study presented at the Digestive Disease Week (DDW) 2008 conference last week in San Diego, researchers assessed the relationship between depletion of gut mucosal CD4 cells and GI symptoms.

Digestive system organs

The investigators studied 32 patients with acute or early HIV-1 infection and 38 control subjects, including 24 with chronic HIV infection and 14 HIV negative individuals. Only 3 of the acutely infected and 2 of the chronically infected patients were receiving antiretroviral therapy at the time of the study.

The researchers collected samples of rectal-sigmoid colon mucosal tissue (obtained via endoscopy) and peripheral blood. Individuals with acute HIV infection underwent endoscopy a mean 39 days after their estimated date of infection (well after resolution of acute retroviral syndrome). Patients with chronic infection had been diagnosed with HIV for a mean of about 7 years at the time of endoscopy.

Mucosal tissue and blood samples were analyzed to determine the percentage of CD4 cells and CD4:CD8 T-cell ratios. GI symptoms, including diarrhea, nausea, and abdominal pain, were noted at the time of endoscopic examination, and the correlation between the presence of these symptoms and virological and immunological parameters was assessed.

Results

• Severe GI mucosal CD4 cell depletion was observed in patients with both acute and chronic HIV infection.

• The mean mucosal CD4:CD8 ratios were 0.29 for acutely infected and 0.08 for chronically infected patients, compared with 1.3 for HIV negative control subjects.

• Despite significant mucosal CD4 cell depletion in acutely infected patients, rates of GI symptoms were low:

• Diarrhea: 6.3%;
• Nausea: 6.3%;
• Abdominal pain: 0%.

• Rates for all 3 GI symptoms were much higher in chronically infected patients:

• Diarrhea: 62.5%;
• Nausea: 33.3%;
• Abdominal pain: 37.5%.

• Factors associated with the development of diarrhea included chronic HIV infection and a past history of opportunistic infections.

• While plasma viral load did not correlate with diarrhea, both mucosal and systemic CD4:CD8 cell ratios did.

• However, diarrhea was more highly correlated with blood CD4:CD8 cell ratio as compared with GI mucosal CD4:CD8 ratio.

Conclusion

Based on these findings, the investigators concluded, "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," they continued. "Development of GI symptoms correlates more strongly with the degree of systemic rather than GI mucosal immune depletion."

5/23/08

Reference
TC Lee, S Mehandru, O Kamalu, and others. Despite mucosal CD4+ T cell depletion, the prevalence of GI symptoms is low during acute and early HIV-1 infection. Digestive Disease Week (DDW) 2008. San Diego, CA. May 17-22, 2008. Abstract W1203.