August 1, 2006 (AIDSmeds)—A University of California research team has discoveredthat HIV is able to survive the antiviral effects of treatment byhiding out in the mucosal tissues of the intestine. Even when bloodtests show that viral load is undetectable and T-cell counts are responding well to HIV treatment, there is likely ongoing viralreplication and immune system damage occurring in the gut. While itsnot 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 toeffectively 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 UCDavis Health System in Davis, California. According to Dr. Dandekar,who is professor and chair of the Department of Medical Microbiologyand Immunology, “The real battle between the virus and exposedindividuals is happening in the gut immediately after viral infection.We need to be focusing our efforts on improving treatment of gut mucosawhere massive destruction of immune cells is occurring.”

Dr.Dendekar explained that gut-associated lymphoid tissue (GALT) accountsfor 70% of the body’s immune system. “Restoring its function is crucialto ridding the body of the virus,” she said.

Last year,Dr. Dandekar published a study of HIV-infected patients who, despitethe lack of treatment, had survived over 10 years with healthy levelsof T-cells and suppressed viral loads. “We looked at their gut lymphoidtissue and did not see loss of T-cells there. This correlated withbetter clinical outcome,” she explained.

Those resultsprompted Dr. Dandekar and her team to undertake the current studyevaluating the effect of combination HIV treatment on viral suppressionand immune restoration in GALT. They followed 10 patients receiving HIVtreatment, taking blood samples and small biopsies of intestinal tissueboth before and after three years of treatment. Three of the patientswere treated within four to six weeks of first being infected with thevirus (patients with primary HIV infection). The other participantswere known to be HIV positive for more than one year (patients whochronic HIV infection).

“We found a substantial delay inthe time that it takes to restore the gut mucosal immune system inthose with chronic infections,” Dr. Dandekar said. “In these patientsthe gut is acting as a viral reservoir that keeps us from riddingpatients of the virus.”

Hoping to figure out why HIVtreatment does not work as well in the gut, Dr. Dandekar’s groupfurther examined the GALT samples collected after at least three yearsof therapy. They found evidence of inflammation, which disrupts tissuefunction, promotes cell death, and upsets the normal balance of gutflora. They also found that the activity of genes that control andpromote mucosal repair and regeneration was suppressed, while the genesresponsible for the inflammatory response were more active than innormal tissue.

GALT samples collected from the threepatients with primary HIV infection – compared to those with chronicHIV infection – suggested that they had fewer signs of inflammation atthe beginning of the study and experienced greater recovery of GALTafter three years of treatment.

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

Theresearchers also suggest that early treatment may be necessary tomaintain the health of GALT, before it is heavily damaged by HIV.According to Thomas Prindiville, MD, a gastroenterologist and co-authorof the study, “What we continue to see is that restoration of immunefunction is more likely when treatment is started early. Startingtreatment before T-cell counts fall below 350, would preserve immunefunction and hasten its full recovery.”

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

Ofcourse, there is a lot more to learn about HIV replication in GALTbefore treatment guidelines are revised or intestinal biopsies arerecommended to people living with HIV and their healthcare providers.Is HIV replication in the gut, while someone is on HIV treatment, acause of drug resistance?Would improved HIV treatment activity in the gut really provide theimmune system with greater protection against AIDS-relatedopportunistic infections? Which HIV medications are most effectiveagainst HIV in GALT? Will early treatment, the use ofanti-inflammatories, and intestinal biopsies actually help HIV-positivepeople live longer, healthier lives? These are just some of thequestions that need to be addressed in clinical trials before thesuggestions of Dr. Dandekar’s group are put into practice.

Dr.Dandekar’s group says that it plans to keep testing ways of improvingthe efficacy of HIV therapy in GALT. This includes studies evaluatingthe treatment of gut inflammation, starting treatment earlier, andusing gut biopsies to monitor treatment success.

“If weare able to restore the gut’s immune response, the patient will be morelikely to clear the virus,” Dr. Prindiville said. He added: “You can’ttreat any infectious disease without the help of the immune system.”