HIV continues to replicate in gut tissue even if potent anti-HIV therapy is effectively controlling virus in the blood, according to a study in the August edition of the Journal of Virology. The study’s authors ponder if HIV-positive individuals taking HIV therapy should have regular gut tissue biopsies, as well as the usual blood tests to check viral load and CD4 cell count, to monitor success of antiretroviral therapy. They also suggest that antiretroviral drugs should be provided soon after infection with HIV to help control long-term inflammation due to HIV in the gut.
It is already well established that a certain type of gastrointestinal tissue called gut associated lymphoid tissue (GALT) is an important early site for HIV replication and CD4 depletion. Investigators from the University of California wished to determine the effect of potent HIV therapy on viral suppression in the gut and its ability to restore the gut’s immune system.
They therefore designed a study involving ten HIV-infected patients. These individuals had both blood samples and gut biopsies taken before, and then three years after they started taking potent HIV therapy. Three of the patients initiated treatment within four to six weeks of first being infected; the remaining individuals had been diagnosed with HIV for at least twelve months.
The investigators found that viral suppression was more effective in the gut tissue of newly infected patients than in those who had been infected for over a year before starting therapy. Newly infected patients had fewer signs of inflammation at the start of the study and the immune function in their gut tissue recovered better. The researchers have followed up more patients since preparing their paper and their unpublished results further support their published findings.
Thomas Prindiville, professor of gastroenterology at the University of California, commented on these findings: “What we continue to see is that restoration of immune function is more likely when treatment is started early.” He added, “starting HAART before T-cell counts fall below 350 cells/mm3 would preserve immune function [in the gut] and hasten its full recovery.’
The Californian investigators also suggest that their data indicates that the effectiveness of HIV therapy could be monitored using gut biopsies. They also believe that immune function could be restored by the earlier initiation of HIV treatment and by the use of anti-inflammatory medication. The investigators maintain that their results indicate that GALT accounts for 70% of the body’s immune system and that it acts as a viral reservoir preventing full eradication of the virus. In support of their findings, they point to work they published last year in HIV-infected people (reference below) who despite having no treatment had survived over a decade with healthy CD4 cell levels and low viral loads. When they looked at samples from their gut they saw no loss of T-cells.
However, the authors accept that having regular gut biopsies taken would be a significant burden to patients. The investigators intend to pursue further research into ways of improving the efficacy of HIV therapy in GALT; the treatment of gut inflammation; and, how to improve the acceptability and effectiveness of using gut biopsies to monitor treatment success.
Guadalupe M et al. Viral suppression and immune restoration in the gastrointestinal mucosa of human immunodeficiency virus type 1-infectred patients initiating therapy during primary or chronic infection. Journal of Virology 80: 8236-8247, 2006.
Sankaran S et al. Gut mucosal T cell responses and gene expression correlate with protection against disease in long-term HIV-1-infected nonprogressors. Proc Natl Acad Sci USA102:9860-9865, 2005.