Treatment News : HIV Hides from Treatment in the Gut - by Tim Horn

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August 1, 2006

HIV Hides from Treatment in the Gut

by Tim Horn

August 1, 2006 (AIDSmeds)—A University of California research team has discovered that HIV is able to survive the antiviral effects of treatment by hiding out in the mucosal tissues of the intestine. Even when blood tests show that viral load is undetectable and T-cell counts are responding well to HIV treatment, there is likely ongoing viral replication and immune system damage occurring in the gut. While its not entirely clear what these findings mean for HIV-positive people, the researchers hint at the possible need for early HIV treatment, intestinal biopsies, and the use of anti-inflammatory medications to effectively manage HIV infection in the gut.

The study, reviewed in the August issue of the Journal of Virology, was conducted by Satya Dandekar, PhD, and her colleagues with the UC Davis Health System in Davis, California. According to Dr. Dandekar, who is professor and chair of the Department of Medical Microbiology and Immunology, "The real battle between the virus and exposed individuals is happening in the gut immediately after viral infection. We need to be focusing our efforts on improving treatment of gut mucosa where massive destruction of immune cells is occurring."

Dr. Dendekar explained that gut-associated lymphoid tissue (GALT) accounts for 70% of the body's immune system. "Restoring its function is crucial to ridding the body of the virus," she said.

Last year, Dr. Dandekar published a study of HIV-infected patients who, despite the lack of treatment, had survived over 10 years with healthy levels of T-cells and suppressed viral loads. "We looked at their gut lymphoid tissue and did not see loss of T-cells there. This correlated with better clinical outcome," she explained.

Those results prompted Dr. Dandekar and her team to undertake the current study evaluating the effect of combination HIV treatment on viral suppression and immune restoration in GALT. They followed 10 patients receiving HIV treatment, taking blood samples and small biopsies of intestinal tissue both before and after three years of treatment. Three of the patients were treated within four to six weeks of first being infected with the virus (patients with primary HIV infection). The other participants were known to be HIV positive for more than one year (patients who chronic HIV infection).

"We found a substantial delay in the time that it takes to restore the gut mucosal immune system in those with chronic infections," Dr. Dandekar said. "In these patients the gut is acting as a viral reservoir that keeps us from ridding patients of the virus."

Hoping to figure out why HIV treatment does not work as well in the gut, Dr. Dandekar's group further examined the GALT samples collected after at least three years of therapy. They found evidence of inflammation, which disrupts tissue function, promotes cell death, and upsets the normal balance of gut flora. They also found that the activity of genes that control and promote mucosal repair and regeneration was suppressed, while the genes responsible for the inflammatory response were more active than in normal tissue.

GALT samples collected from the three patients with primary HIV infection – compared to those with chronic HIV infection – suggested that they had fewer signs of inflammation at the beginning of the study and experienced greater recovery of GALT after three years of treatment.

Based on these findings, Dr. Dandekar and the other authors suggest that anti-inflammatory drugs may improve HIV treatment outcomes, although no specific anti-inflammatory recommendations are made.

The researchers also suggest that early treatment may be necessary to maintain the health of GALT, before it is heavily damaged by HIV. According to Thomas Prindiville, MD, a gastroenterologist and co-author of the study, "What we continue to see is that restoration of immune function is more likely when treatment is started early. Starting treatment before T-cell counts fall below 350, would preserve immune function and hasten its full recovery."

To measure the effects of early treatment and anti-inflammatory therapy on the gut, Dr. Dandekar's group indicates that intestinal biopsies may be necessary. Blood measurements of viral load and T-cell counts, she says, do not provide an accurate picture of what is going on in GALT.

Of course, there is a lot more to learn about HIV replication in GALT before treatment guidelines are revised or intestinal biopsies are recommended to people living with HIV and their healthcare providers. Is HIV replication in the gut, while someone is on HIV treatment, a cause of drug resistance? Would improved HIV treatment activity in the gut really provide the immune system with greater protection against AIDS-related opportunistic infections? Which HIV medications are most effective against HIV in GALT? Will early treatment, the use of anti-inflammatories, and intestinal biopsies actually help HIV-positive people live longer, healthier lives? These are just some of the questions that need to be addressed in clinical trials before the suggestions of Dr. Dandekar's group are put into practice.

Dr. Dandekar's group says that it plans to keep testing ways of improving the efficacy of HIV therapy in GALT. This includes studies evaluating the treatment of gut inflammation, starting treatment earlier, and using gut biopsies to monitor treatment success.

"If we are able to restore the gut's immune response, the patient will be more likely to clear the virus," Dr. Prindiville said. He added: "You can't treat any infectious disease without the help of the immune system."

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