Core and Cohort Updates
This spring season has been incredibly busy for the Admin Core. Since our last issue, the URBAN ARCH Training and Mentoring Event and DSMB Meeting were both successfully held virtually on March 16 and 17. The URBAN ARCH Admin Core appreciated the valuable feedback from DSMB members, and looks forward to the next meeting which has been scheduled for September 28, 2021.
During the URBAN ARCH Training and Mentoring Event, mentors presented career and research advice, mentors and trainees were able to connect virtually for one-on-one discussions, and individual specific aims feedback was provided by our very own Dr. Judy Hahn. We look forward to providing additional mentoring and networking opportunities for trainees in the future. Please check out our main story for specific advice shared by mentors during this event!
The team has spent many hours in the URBAN ARCH sample repository preparing for, sending, and receiving sample shipments. The final shipment from St. Petersburg, Russia containing plasma, serum, peripheral blood mononuclear cells, nasal, fecal, and dried blood spot samples was received on May 11. On May 18, one large shipment of plasma and serum samples was successfully sent to the University of Vermont for biomarker testing. A shipment of Uganda ADEPT DBS Cards was sent to UCSF for PEth testing and a shipment of plasma went to the Miriam Hospital in Providence. The team has multiple repository requests underway and in queue to be sent to the University of Toronto, Cleveland Heart Lab, and Boston University. For more information on the URBAN ARCH sample repository, please visit our webpage. If you have questions regarding the URBAN ARCH repository, please contact Natalia Gnatienko.
The BDM Core has been working on multiple analyses and manuscripts across URBAN ARCH including the main analyses for both St PETER and the Boston 4F study. BDM faculty statistician Sara Lodi recently published 2 papers as lead author—the Per Protocol analyses for the ZINC trial and the protocol paper for the DIPT trial.
The ADEPTT study concluded enrollment in January of 2020 with 302 participants, including 155 females and 147 males. Of these, 200 are current alcohol drinkers and 102 are alcohol abstainers. To achieve our enrollment, we screened 1,434 patients from the Mbarara ISS Clinic, of whom 1,312 were consented for further screening for latent TB. Out of 1,192 PPD placements completed, 308 (26%) participants had positive results for latent TB and were eligible for the study and 302 enrolled.
All data collection for the ADEPTT study ended on April 1, 2021. We completed baseline procedures for all 302 participants enrolled, 295 month-3 visits, 292 month-6 visits, 289 month-12 visits, 271 month-18 visits, 170 month-24 visits, 134 month-30 visits, 78 month-36 visits, and 35 month-42 visits. Twenty-six participants discontinued TB preventive therapy (INH) due to grade 3/4 level toxicities and three women discontinued INH due to being pregnant. Two participants are deceased, and the cause of death was unrelated to the study. Two participants were diagnosed with active pulmonary tuberculosis. Two-hundred and eighty-six participants have completed all study activities and have graduated from the study. We are in the process of completing analyses and the manuscript for the ADEPTT main aims.
We have enrolled 48 participants in the Uganda cohort of our COVID-19 administrative supplement looking at changes in alcohol use, ART levels, and viral suppression before, during, and after stay-home restrictions in PLWH in Uganda and Boston.
The main aims of this randomized controlled trial are to examine whether economic incentives provided to HIV/TB co-infected heavy drinkers can reduce alcohol use and increase adherence to isoniazid preventive therapy (IPT). The DIPT study is progressing well. As of June 1, 2021, we have enrolled 660 participants out of our and target enrollment of 680. We have screened 5,100 individuals, of whom 3,859 were further screened to determine heavy drinking status using the point-of-care ethyl glucuronide (EtG) test. Out of the 3,443 who completed EtG testing, 1,913 (50%) were EtG positive. Of those who were EtG-positive, we placed 1,701 purified protein derivative (PPD) skin tests to confirm latent TB status. From this, 681 (40%) participants had positive results for latent TB and were eligible for the study. Overall, we have enrolled 660 participants who are EtG-confirmed heavy drinkers with latent TB. Enrollment is expected to conclude by August 1st.
The main aims of the EXTEND RCT are to estimate the uptake and acceptability, preliminary efficacy, and cost of methods of delivery of an intervention to reduce unhealthy drinking and HIV viral failure among persons in HIV care in rural Uganda (n=270). We concluded enrollment in this study at the end of December 2020 with 273 participants, (270 participants plus 3 pilot participants). Of the 273 participants enrolled in the RCT, 181 were male and 92 were female, 91 were randomized to arm 1 (in-persons counseling plus live call boosters); 91 were randomized to arm 2 (in-person counseling plus automated boosters); and 91 were randomized to arm 3 (standard of care, wait-list control). Participants in arm 2 (automated boosters) are given a choice between Interactive Voice Response (IVR) or Short Message service (SMS) messages for their booster sessions and approximately two thirds (65) of them chose IVR while about one third (29) of them chose SMS as their preferred automated booster message delivery option.
The St PETER COVID study continues to recruit participants from the St PETER parent study. As of June 1, 2021, a total of 112 participants completed the study assessment, which aims to evaluate the effects of the pandemic on alcohol and tobacco use.
As of June 1, 2021, the PETER PAIN UH3 study randomized 15/45 participants into one of three arms: gabapentin, low-dose naltrexone, or placebo. The aim of the study is to assess the effectiveness of novel pharmacotherapies to improve chronic pain among HIV-positive heavy drinkers.
The HIV Latency study completed sample collection in March 2021 and is now in the process of completing data analysis. The aim of the study is to characterize the effects of opioid use disorder on host immune function, HIV replication, and HIV latency.
In May, the team received the final shipment of samples for the St PETER, TMAO, ACME, and HIV Latency studies (whole blood, PBMC, plasma, serum, DBS cards, fecal samples) from Russia. Samples will be shipped to various institutions that will conduct tests, including biomarkers.
On May 14, 2021, co-investigator Dr. Dmitry Lioznov presented to the team and collaborators on the current HIV situation in Russia. If you are interested in viewing the recording of the presentation, please email firstname.lastname@example.org.
The team is actively pursuing data analyses, abstract submissions, and manuscript preparation.
- Tindle HA, et al. Results from a randomized controlled trial of smoking cessation medications for alcohol reduction among HIV-positive heavy drinkers and daily smokers in St. Petersburg, Russia. Accepted to International AIDS Society 2021.
- Mensah SO, et al. Alcohol, HIV and trimethylamine-n-oxide (TMAO) levels. Accepted to RSA/ISBRA-2021 Scientific Meeting.
- Tandon S, et al. Whole metagenome sequencing to explore change in abundance of butyrate-producing genes in gut microbiota of people with HIV who reduce alcohol consumption. Accepted to RSA/ISBRA-2021 Scientific Meeting.
- Singhal R, et al. Microbial dysbiosis in people living with HIV (PLWH) who are heavy alcohol drinkers is marked by a decrease in butyrate producing bacteria. Accepted to RSA/ISBRA-2021 Scientific Meeting.
- Ghare S, et al. Targeted metabolic profiling of plasma bile acids in people living with HIV (PLWH) who are heavy drinkers. Accepted to RSA/ISBRA-2021 Scientific Meeting.
- Rossi SL, et al. COVID-19 pandemic-related stress and substance use behaviors among people with HIV in St. Petersburg, Russia. Accepted to 2021 NIDA International Forum.
- Toussova O, et al. Engagement of HIV-positive people who inject drugs in Acceptance and Commitment Therapy (ACT) as a stigma coping group intervention in St. Petersburg, Russia. Accepted to 2021 NIDA International Forum.
- Corcorran MA, Ludwig-Baron N, Cheng DM, Lioznov D, Gnatienko N, Patts G, So-Armah K, Blokhina E, Bendiks S, Krupitsky EM, Samet JH, Tsui JI. The Hepatitis C continuum of care among HIV-positive persons with heavy alcohol use in St. Petersburg, Russia. AIDS Behav. 2021 Mar 17. Epub ahead of print.
- Lodi S, Freiberg M, Gnatienko N, Blokhina E, Yaroslavtseva T, Krupitsky E, Murray E, Samet JH, Cheng DM. Per-protocol analysis of the ZINC trial for HIV disease among alcohol users. Trials. 2021; 22(1):1-7. PMCID: PMC7989012
- Hahn JA, Murnane PM, Vittinghoff E, Muyindike WR, Emenyonu NI, Fatch R, Chamie G, Haberer JE, Francis JM, Kapiga S, Jacobson K, Myers B, Couture MC, DiClemente RJ, Brown JL, So-Armah K, Sulkowski M, Marcus GM, Woolf-King S, Cook RL, Richards VL, Molina P, Ferguson T, Welsh D, Piano MR, Phillips SA, Stewart S, Afshar M, Page K, McGinnis K, Fiellin DA, Justice AC, Bryant K, Saitz R. Factors associated with phosphatidylethanol (PEth) sensitivity for detecting unhealthy alcohol use: An individual patient data meta-analysis. Alcohol Clin Exp Res. 2021 Apr 10. Epub ahead of print.
- Fuster D, So-Armah K, Cheng DM, Coleman SM, Gnatienko N, Lioznov D, Krupitsky EM, Freiberg MS, Samet JH.Lack of association between recent cannabis use and advanced liver fibrosis among HIV-positive heavy drinkers. Curr HIV Res. 2021 May 19. Epub ahead of print.
In February 2021, the Boston ARCH: 4F Cohort concluded study recruitment, with a final cohort of 251 participants (176 participants from the original Boston ARCH Bone Cohort and 75 participants new to the cohort). Follow-up assessment, which began in June 2018, is ongoing. As of June 1, 2021, 233 6-month follow-up phone interviews, 207 12-month annual follow-up visits, 173 18-month interim follow-up phone interviews, 111 24-month annual follow-up visits, 83 30-month follow-up phone interviews, and 23 36-month annual follow-up visits have been completed.
Following the conclusion of the collection and analysis of qualitative data used to inform the development of a fall prevention intervention tailored for people with HIV, alcohol use, and at risk of falls, we developed a protocol for a pilot feasibility study of the intervention. We submitted the study protocol for review and approval by the Boston University Medical Campus Institutional Review Board (IRB). The study aims to enroll 40 participants who will be randomized to either the intervention group (receiving the fall prevention intervention) or a control group. After the study protocol is IRB-approved, participant recruitment and enrollment will begin.
In September 2020 we were awarded supplemental funding from NIAAA to expand the scope of our existing Boston ARCH: 4F Cohort study to assess the impact of the COVID-19 pandemic and the effects of physical (social) distancing and other mitigation strategies on substance use (heavy alcohol use and/or other drug use including nonmedical prescription medication use) and HIV medication adherence among people living with HIV. As of June 1, 2021, study staff have administered 35 baseline supplemental COVID-19 specific assessments to Boston ARCH: 4F Cohort participants.
Furthermore, the Uganda cohort received funding for a COVID-19 related administrative supplement in September 2020. With this funding, hair and dried blood spot samples will be collected from participants in the Boston and Uganda cohorts to examine biomarkers for change in participants’ alcohol use, antiretroviral therapy (ART) levels, and viral suppression before, during, and after COVID pandemic-related stay-at-home restrictions. The Boston ARCH: 4F Cohort study has received approval to collect these additional biospecimen samples by the Boston University Medical Campus IRB, and biospecimen sample collection will begin this month.