The Fire Within: Research on Two Supplements Addresses HIV-Driven Inflammation in the Gut. 31/10/2013

Probiotic Supplementation Could Potentially Decrease Resistance, Micronutrient Deficiencies, Viral Replication and Immune Suppression

Gastrointestinal (GI) health is proving to be a vital, though often ignored, component of HIV infection. Recent research presented at the 7th International AIDS Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2013) that took place this past July in Kuala Lumpur, Malaysia showed that microbial translocation and the damage done to gut-associated lymphoid tissue (GALT) during primary HIV infection has a dramatic effect on the pathogenesis of HIV, including the disruption of microflora, resulting in ongoing and damaging inflammation. While more research on the effects of HIV on the GI system is sorely needed, the consequences of sequestration on the National Institutes of Health (NIH) budget, along with the growing competition to prioritize directions in therapeutic investigation, ranging from viral host restrictive factors to preventive vaccines, makes putting anything else on the table an enormous challenge.

The data being presented on addressing microbial translocation, HIV-associated enteropathy and gut inflammation is compelling. HIV-associated enteropathy often accounts for diarrhea and malabsorption in patients who lack an identifiable cause and includes mucosal dysfunction as a defining characteristic. HIV-associated enteropathy results in microbial translocation and subsequent chronic inflammation as well as malabsorption, which may result in drug resistance.

HIV-associated enteropathy affected a high percentage of people with HIV in the pre-HAART (highly active antiretroviral therapy) era and continues to be a problem for some even in the presence of HAART. HIV-associated enteropathy can cause weight loss and structural and functional damage to the GI tract. Despite effective treatment with HAART, it continues to be drastically underestimated.

The only available drug for HIV-related non-infectious diarrhea is Fulyzaq. Fulyzaq, made by Salix Pharmaceuticals, was approved by the U.S. Food and Drug Administration (FDA) in 2012. In a 374-patient study, incidences of diarrhea were reviewed over a 20-week period. Results found that 17.6% of patients taking Fulyzaq had two or less watery bowel movements per week compared to only 8% of patients on placebo. Fulyzaq was found to be less effective in African Americans who participated in the study. Due to continual production issues, this drug is not widely available and appears to only help a small number of people.

Few other potential treatments for HIV-associated enteropathy are currently being studied despite the great need for interventions. One study, however, that showed promise was published in the journal AIDS (Asmuth et al., 2013) and presented at the 19th International AIDS Conference (AIDS 2012) last July in Washington, DC and the 20th Conference on Retroviruses and Opportunistic Infections (CROI 2013) in March of this year in Atlanta, GA. Dr. David Asmuth reported on a pilot study of the effects of serum-derived bovine immunoglobulin / protein isolate (SBI), EnteraGam, made by Entera Health, on patients with HIV-associated enteropathy. According to previous studies in porcine and murine models, EnteraGam has been shown to improve gut health and function and reduce markers of inflammation.

All eight participants in this study were on HAART. Administration of EnteraGam improved GI absorption and increased the density of CD4 T lymphocytes in GALT. Although markers of microbial translocation remained unchanged, D-Xylose, a direct measure of proximal small bowel function, suggested improvement in diarrhea in seven out of eight study participants. The utility of EnteraGa was significantly associated with increased intestinal CD4+ cell counts and function and demonstrated evidence of intestinal repair in patients experiencing HIV-associated enteropathy. A longer, larger, blinded study is said to be forthcoming on this medical food.

Another approach to addressing HIV-associated enteropathy is the utility of probiotics. AIDS Healthcare Foundation (AHF) conducted a study on GanedenBC30 that found that supplementation with the probiotic increased CD4+ cell counts.

"We are learning more and more about the interaction between our gut and our immune system. It is such complex machinery that keeps bacteria inside the intestines and, in a majority of the cases, very tightly controlled. Occasionally it gets out of control and that's why people get illnesses. There is more and more evidence that most likely some fragments of bacteria occasionally escape -- they make their way to our systemic circulation, our bloodstream -- and, of course, being a foreign object, the body will try to attack it and neutralize it. That leads to inflammation," Dr. Homayoon Khanlou, M.D., chief of medicine at AHF and lead investigator of this pilot study, stated in an article which appeared in A&U magazine.

Inflammation in the gut can cause bone loss and probiotics can improve bone density. A new study from Michigan State University sponsored by the NIH published in the Journal of Cellular Physiology found that probiotic supplementation utilizing lactobacillus reuteri, a probiotic shown to reduce inflammation, produced healthier bones. Lead author Dr. Laura McCabe, professor of physiology and radiology at Michigan State University, said, "We know that inflammation in the gut can cause bone loss, though it's unclear exactly why."

Studies by the AIDS Clinical Trials Group (ACTG) on new interventions for HIV-associated enteropathy, as well as other HIV associated GI conditions are long overdue. With the formation of the Delaney AIDS Research Enterprise at the NIH, the opportunities to advance research on gut inflammation, its effect on HIV pathogenesis and HIV's mechanisms for evading viral host restrictive factors have never been better.

With more data being generated on interventions such as EnteraGam and GanedenBC30 in HIV patients, the real question confronting state legislators is ensuring access to care by implementing exception to policy in public health insurance programs such as Medicaid. These supplements could be made available to patients through state enteral formularies. In these times of sequestration, cost-effective measures are of more importance than ever. Therapeutic supplementation has proven to be among the best of these interventions.

An unspoken complication of HIV-associated enteropathy is the disruption in treatment pharmacokinetics, which is the difference between successful and unsuccessful treatment. As the efficacy of these drugs is dependent upon nutritional status, the subsequent malabsorption results in varying levels of the drug in the blood that could predictably result in treatment failure.

HIV-associated enteropathy may be one of the driving factors behind the deeply disturbing data presented at AIDS 2012 by the U.S. Centers for Disease Control and Prevention (CDC) that three out of every four people living with HIV in the U.S. are not able to achieve durable viral suppression. Addressing this alarming condition in a cost-effective manner is of critical importance to achieving widespread viral suppression, which in turn would decrease the number of new HIV infections.

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