Where’s the Sustained Research on GI Health?
by Mariel Selbovitz, MPH, and David Miller
While “Getting to Zero” and “AIDS-free Generation” have become the new catch phrases of the AIDS crisis of late, the harsh reality exposed by the CDC’s report—that three out of every four people living with HIV in the U.S. are unable to keep their virus under control—means that the urgency can no longer be denied. Successful management of HIV, despite one-pill-once-a-day treatments, goes beyond viral suppression. There are lots of reasons why patients are failing their HAART regimens or not entering treatment and care early enough. Restoring and maintaining a viable immune system and successfully addressing HIV-related noncommunicable diseases requires clinical innovations and advances in our current approach to treating HIV.
HIV-associated enteropathy is typically mistaken for a side effect of ARVs, which can exhibit, in part, the same symptoms (diarrhea, malabsorption and weight loss). While an endoscopy is the best means for diagnosing HIV-associated enteropathy, the procedure, while cost-effective, is typically not being applied by primary care physicians. Patients can wait months for an appointment with a GI specialist, during which time variations in the pharmacology of their antiretroviral therapy can vary greatly due to malabsorption, one of the conditions caused by HIV-associated enteropathy.
HIV inflammation has become a hot topic for researchers, with more studies being introduced than ever before. However, the issues of gut health and inflammation from microbial translocation are still not getting the attention needed to make a significant difference, despite several studies on gut health and HIV that have shown dramatic improvements in clinical outcomes. HIV-associated enteropathy is a condition involving increased GI inflammation, altered barrier function, and increased intestinal permeability. Malabsorption of nutrients can be a result of HIV enteropathy. HIV-associated enteropathy is caused by acute infection and continues through the course of HIV, even in the presence of HAART, causing both structural and functional damage to the GI tract.
At AIDS 2012, Dr. David Asmuth presented on an eight-patient, eight-week pilot study of Serum-derived bovine immunoglobulin/protein isolate (SBI) in HIV patients on HAART, the results of which have recently been published in the journal, AIDS. The study found that administration of SBI improved GI absorption and increased the density of CD4+ T lymphocytes in gut-associated lymphoid tissue (GALT). A larger and longer study is currently underway to determine how SBI works to improve immune reconstitution in GALT and address HIV-associated enteropathy. SBI is expected to be available under the brand name EnteraGam (made by Entera) as a prescription medical food indicated for the clinical dietary management of enteropathies such as those associated with HIV under medical supervision later on this year.
In December 2012, the first drug to treat diarrhea in HIV patients, Fulyzaq (crofelemer), was approved by the FDA. The drug requires a prescription and is an anti-diarrheal indicated for the symptomatic relief of non-infectious diarrhea in adult patients with HIV/AIDS on antiretroviral therapy. Unfortunately this approved drug has not yet reached the market in wide distribution due to production delays. Therefore, there is currently no drug treatment for HIV-associated enteropathy available to HIV-infected patients afflicted with chronic and debilitating diarrhea.
Publicly sponsored HIV research networks such as the Canadian HIV Trials Network, AIDS Clinical Trials Groups, and European AIDS Trials Network have not done much work in HIV-related diarrhea and enteropathy, leaving not only the question of the epidemiology unanswered but also perpetuating the lack of interest in deciphering a more definitive understanding of the role HIV-associated enteropathy may be playing in the incomplete restoration of the immune system. Despite ongoing concern about maximizing clinical outcomes in HIV patients and well-defined research agendas, HIV-associated enteropathy, like pulmonary hypertension, the correlations with lypodystrophy and cardiovascular disease and a dozen other clinical concerns negatively affecting quality of life for patients, doesn’t seem to generate the necessary appeal to primary investigators to research aggressively. One of the questions that could be answered with substantial investigation of HIV-associated enteropathy is whether variations in the absorption in ARVs due to extensive diarrhea could lead to increased risk of drug resistance and effects on GALT, which according to several leading researchers, is one of the determinants of long-term survival.
We have seen time and time again that addressing HIV-associated conditions proactively leads towards making HIV more manageable, decreases costs, and improves clinical outcomes. Side effects from ARVs and the damage caused in the gut by HIV are very well-defined. Studies of probiotics and HIV have shown potential and warrant further investigation. One such study, conducted with AIDS Healthcare Foundation, demonstrated benefits such as less incidence and severity of diarrhea episodes and an increase in CD4 counts. However a financial and regulatory barrier exists in access to dietary supplements and medical foods.
So what can we do?
As patients, advocates, activists, and interested parties, we can demand standards of care be provided that ensure access to GI specialists early on to assess whether or not GI problems may predispose a patient to SAEs from ARVs. We can demand research priorities be inclusive of gut health and support patient literacy and clinician awareness. We can also ensure there are dedicated tracks at leading conferences, such as the upcoming XX International AIDS Conference, that focus on these issues.
Mariel Selbovitz, MPH, serves as the Chair of the Cornell ACTG Community Advisory Board and has authored over thirty abstracts and articles.
A former member of ACT UP NY, David Miller is an AIDS treatment activist and current member of the Cornell ACTG CAB.