Microbiome, mETabolites, and Alcohol in HIV to reduce CVD Randomized Control Trial (META HIV CVD RCT)

The META HIV CVD RCT is a two-arm trial (n=125 per arm) that will assess whether a probiotic containing multiple strains of bacteria supporting butyrate synthesis compared to placebo mitigates dysbiosis. This 6 month trial will be among PWH who are heavy drinkers, on ART, and with a CD4 cell count ≥350 cells/mm3. The trial will also assess dysbiosis metabolites, microbial translocation and inflammation, CVD and mortality risk, alcohol consumption and HIV disease progression. Participants will be recruited from the prior ACME HIV study at Pavlov State Medical University in St. Petersburg, Russia. All participants will receive brief evidenced based counseling for alcohol consumption. We will collect survey data, fecal specimens, and phlebotomy via 5 in-person study visits, up to 18 months from baseline.

This project will compare the effects of a tailored probiotic vs. placebo at 6 months on

  • (Aim 1) dysbiosis (fecal Firmicutes to Bacteroidetes (F/B) ratio, primary study outcome; fecal Lachnospiraceae-family of butyrate producers) and plasma metabolites (plasma butyrate, deoxycholic acid:cholic acid ratio, and TMAO);
  • (Aim 2) biomarkers of inflammation (plasma, IL-6, D-dimer, sCD14), microbial translocation [Lipopolysaccharide binding protein];
  • (Aim 3) cardiovascular risk (Reynolds risk score), mortality risk (VACS index); and
  • (Aim 4 exploratory) alcohol consumption (% heavy drinking days in past month) and HIV disease progression (CD4 cell count).

We hypothesize that as compared with placebo, the probiotic arm will have significantly:

  • (1) higher F/B ratio and levels of fecal Lachnospiraceae, plasma butyrate, deoxycholic acid: cholic acid ratio and lower levels of TMAO;
  • (2) lower plasma biomarker levels of microbial translocation and inflammation;
  • (3) lower Reynolds risk score and VACS index;
  • (4) lower % heavy drinking days in the past month and higher CD4 cell counts.

The findings from this RCT will inform probiotics’ role as standard adjunctive therapy complementing alcohol interventions among PWH who are heavy drinkers.

Spotlight on Elena Blokhina, MD, PhD

Dr. Blokhina was interviewed by Asri Mumpuni on December 8, 2021. She serves as a co-investigator for Project 1, titled Microbiome, mETabolites, and Alcohol in HIV to reduce CVD Randomized Control Trial (META HIV CVD RCT).

Is there anything you would like to highlight from the specific aims of this project?

I would like to highlight AIM 2 to compare the effects of a tailored probiotic vs. placebo at 6 months on biomarkers of inflammation (plasma, IL-6, D-dimer, sCD14), and microbial translocation [Lipopolysaccharide binding protein]. Reaching this goal will help us to understand the role of the microbiome in systemic inflammation and determine if it is possible to influence it by adding probiotics. We hope to be able to find a rather simple way to prevent CVD in people with HIV (PWH). 

What has it been like to be part of an international collaboration? How do you think the field can benefit from by working with partners globally?

I am proud to be a part of such a great international team. I think we all benefit from this collaboration. We share ideas and experiences, and together we can test interesting hypotheses. There are more than 1 million PWH in Russia and a lot of them are not getting HIV care so we can test new treatment approaches that can be implemented globally.

What has your experience been during this early stage of starting out the RCT? Are there any aspects you have enjoyed most? Are there lessons learned you would like to share?

It is very interesting, but always challenging to organize it properly and not to miss anything. In this process I enjoy learning something new, to overcome difficulties and to make impossible things possible. At an early stage of an RCT, from my perspective, it is important to share all concerns and to come up with a plan of how to deal with them. It will help the RCT to go smoothly and to reach our study goals.

Have you had any new hobbies or interests since your last spotlight when you talked about playing tennis with your husband?

I have been forced to take a break from playing tennis because of an injury. My new hobby is painting furniture. About two years ago, I realized that we have a lot of IKEA furniture in our apartment. I like it but it’s very popular, and you can find the same piece of furniture in St Petersburg, Amsterdam and Boston. I wanted to add a little personality with painting. So I took an online course and started with a small stool. It was not as easy as I assumed but it did not become an epic fail. Now I have two years of practice and about 10 painted pieces. The last one is a buffet which from wooden color became navy blue. I like it much more now.