HIV Evades Antiretroviral Therapy by Hiding in the Gut
Viral suppression key to restoring mucosal immune system activity
WEDNESDAY, Aug. 2 (HealthDay News) -- HIV evades highly active antiretroviral therapy (HAART) in infected patients by hiding in gut-associated lymphoid tissue, according to a report in the August issue of the Journal of Virology. Suppression of viral replication and control of inflammatory responses in the gut may be key to restoring mucosal immune system function during HAART.
Satya Dandekar, Ph.D., and colleagues from the University of California-Davis School of Medicine evaluated viral suppression, CD4+ T-cell restoration, gene expression, and HIV-specific CD8+ T-cell responses in gastrointestinal biopsy and blood samples from 10 patients initiating HAART during primary or chronic HIV infection. The researchers used flow cytometry, real-time PCR, and DNA microarray analysis.
The investigators found that the virus continues to replicate in gut tissue despite a drop in plasma viral load. HAART seemed to be more effective in newly infected patients than those with chronic infection and correlated with lower CD8+ T-cell responses. Genes responsible for growth and repair were suppressed while genes responsible for inflammation and cell activation were upregulated in patients who did not replenish mucosal CD4+ T-cells efficiently.
"Our results emphasize the importance of monitoring gut-associated lymphoid tissue in the evaluation of immune restoration during therapy as well as the need for developing novel therapeutic strategies to enhance the repair and regeneration of the mucosal immune system," Dandekar and colleagues conclude.