Can Probiotics Actually Slow the Progression of HIV?

Research over the past few years has discovered that microbes (bacteria) found in the gut play an important role in HIV disease progression and pathogenesis. Two new studies are currently enrolling participants to determine if probiotics can alter this damaging process and, in turn, reduce HIV disease progression.

During initial HIV infection, the first and most catastrophic onslaught to the immune system occurs in the gut where 60-70 percent of the immune system resides, including two- thirds of CD4 cells. Certain CD4 cells, called TH17 cells, help to protect the integrity of the gastrointestinal wall from a process called microbial translocation. This process occurs where the gut mucosal integrity is breached and microbes from the microbiome (communities of bacteria) and some of their products leak through the gut wall, enabling them to circulate within the bloodstream. When this occurs, the immune system responds by attacking the microbes, causing systemic inflammation. This persistent inflammation contributes to the occurrence of non AIDS-related conditions such as cardiovascular disease and certain cancers.

In addition to microbial translocation, dysbiosis occurs within the microbiome during HIV infection. Billions of bacteria exist in and on the human body. These bacteria gather in the microbiome where various strains of bacteria, both ‘good’ and ‘bad’, exist in a symbiotic state. Microbiome dysbiosis is a disruption of this balance within the gastrointestinal tract. Dysbiosis can lead to a decrease in CD4 cells, as well as further microbial translocation and local and systemic inflammation.

At The Conference on Retroviruses and Opportunistic Infections this past February, several studies examined the role of the microbiome in HIV pathogenesis and progression. One study conducted at the University of Wisconsin–Madison, in monkeys infected with SIV, demonstrated a marked increase of bacteria in the blood stream immediately following SIV infection. Once the immune system began to gain some control over SIV at least partly mediated by improved TH17 cell gut immune function, the amount of circulating bacteria in the blood stream declined dramatically with concomitant decreases in markers of inflammation. Study researchers hypothesized that greater control of bacterial translocation during this stage, and lower initial inflammation, may lower viral set points and limit the seeding of viral reservoirs. This study illustrates how the immune system and gut microbiome interface and HIV infection may increase the damaging effects of normally symbiotic bacteria.

Another presentation at CROI 2016, based out of the Sapienza University of Rome, studied the effects that a six month course of probiotics had on microbial translocation in ten HIV- positive men on antiretroviral therapy. This study showed considerable recovery of TH17 and TH1 (Type 1 T-helper cells which play many important roles in the immune defense) cell populations in both the gut and peripheral blood, as well as a reduction in cellular markers of immune activation. This data indicates the potential benefits of probiotics to decrease systemic inflammation.

Probiotics have been used in the general population to promote a healthy microbial balance and have been studied in diseases such as irritable bowel syndrome and inflammatory bowel diseases. Small Probiotic studies in HIV-infected persons have been conducted, but results have yet to definitively determine the benefits and safety of probiotic use in HIV-positive patients.

Probiotic use is being further examined in a placebo controlled study of 90 HIV- positive individuals on stable antiretroviral therapy. The NIH sponsored AIDS Clinical Trails Group (ACTG) study will enroll participants from several U.S. sites including The University of Alabama at Birmingham and the John Hopkins University in Baltimore.

According to Adriana Andrade MD, MPH, FACP, Associate Professor of Medicine at Johns Hopkins and Co-Chair for this study, “The recognition that HIV induces a dysbiotic state in the GI tract with immune and inflammatory consequences has created a need for research to evaluate treatments to improve the gut microbiome diversity and the integrity of the gut mucosal. There is significant interest in these studies in the HIV community, yet the studies performed to date have not been adequately powered to evaluate the effects of probiotics. ACTG A5350 is a well-designed, peer reviewed protocol which has also been reviewed by our community partners. It will greatly enhance our understanding of the interactions between HIV, the gut microbiome, and HIV-related inflammation/immune dysfunction.”

In ACTG A5350, a probiotic called Visbiome (made by Exegi Pharma), which is a mix of four strains of Lactobacilli, three strains of Bifidobacteria, and one strain of Streptococcus thermophilus will be assessed in individuals with suppressed viral loads and CD4 counts above 200. The study will determine if Visbiome:

Reduces systemic inflammatory markers
Increase microbe diversity in the gut microbiome
Improve immune function in the gut

There are numerous probiotic formulations, each one with different bacterial strains. Determining which strains will be beneficial to HIV-infected individuals means studying each formulation to determine its safety and efficacy. “The formulation in Visbiome has been demonstrated to replete the CD4 cell population in the gut of SIV-infected macaques which were administered the probiotic blend. Furthermore, inflammation in the gut was markedly decreased with the formulation administration. Given these results and human studies demonstrating the benefit of the formulation found in Visbiome to improve bowel symptoms in inflammatory bowel diseases, this probiotic has the potential to positively impact HIV disease outcomes,” stated Dr. Turner Overton, Associate Professor of Medicine at The University of Alabama at Birmingham and Co-Chair for this study.

A separate study of the same probiotic is also enrolling at two sites in Toronto, Canada. This study is primarily looking to see if immune activation, inflammation and microbial translocation can be positively affected by the probiotic. It’s enrolling men who are virally suppressed with a CD4 count that is below 350, as well as those who are treatment-naïve and ready to begin antiretroviral therapy. It’s hypothesized that probiotics, in this case Visbiome, may boost the immune function for these individuals.

As with the ACTG study, this study was spurred by recent research on the important role the microbiome plays in HIV disease and the potential that probiotics may have in this process. Rupert Kahn, Primary Investigator and Clinician Scientist at the University Health stated, “We are very excited to work with the HIV community on this trial, since clinical testing of complementary therapies has been identified as a research priority by people living with HIV in Ontario, and the preliminary probiotic work in primate models has been so promising.”

If you’re interested in enrolling in this study you can contact: Erika Benko, Research Coordinator at the Maple Leaf Medical Clinic at (416) 465-3252 x 4 or ebenko@mlmedical.com. For information on enrolling in ACTG A5350 please go to the trial site on ClinicalTrials.gov to identify a site in your area.