International URBAN ARCH Center Core and Project Updates

Administrative Core

The Admin Core successfully executed the International URBAN ARCH Center fall Program Advisory Committee (PAC) meeting in early October, updating our PAC on core/project activities and progress. Later in October, we were excited to help welcome Dr. Conrad Muzoora, Associate Professor and Research Fellow at Mbarara University of Science and Technnology, to Boston for two presentations on TB diagnostics and treatment in Uganda. Dr. Nneka Emenyonu, Project Director for the TRAC study, accompanied Dr. Muzoora in Boston and the Admin Core facilitated meetings with Dr. Muzoora, Dr. Emenyonu, and collaborators.

Dr. Emenyonu, Dr. Muzoora, and TALC study co-investigator Dr. Karen Jacobson at the Tuberculosis Interdisciplinary Approach to Research Alliance (TIARA) TB Interest Group seminar on October 17.

Dr. Emenyonu met with TRAC/TALC biostatistician Dr. Fatema Shafie Khorassani.

The Admin Core also supported the TALC, TRAC, and GRAIL teams in the planning of a successful site visit to Mbarara in November.

We look forward to our next quarterly Visiting Scholar Research-in-Progress webinar on Wednesday, February 26 at 11am ET/10am CT/8am PT. Drs. Sylvie Naar and Karen MacDonell will present progress and emerging results from the Self-Management of HIV and Alcohol Reaching Emerging Adults (SHARE) P01 program. Register here to join us for this virtual webinar.

Biostatistics and Data Management Core

The BDM Core is thrilled to welcome two new biostatisticians: Dr. Fatema Shafie Khorassani, Assistant Professor of Biostatistics at BUSPH, who will now serve as lead statistician for both the TALC & TRAC studies and Dr. Huimin Cheng, Assistant Professor of Biostatistics at BUSPH, who will serve as lead statistician for the GRAIL study. Data management activities, including derived variable creation and documentation, are ongoing for TRAC, GRAIL, and TALC. The BDM Core supported the development of analytic plans for both the TRAC and TALC studies. In addition, the core collaborated on several analyses for abstracts submitted to the following conferences: Conference on Retroviruses and Opportunistic Infections (CROI), the International Union against Tuberculosis and Lung Disease, North America Region (Union NAR) conference, and the Mbarara University of Science & Technology (MUST) conference.

TB Risk by Alcohol Consumption (TRAC) Study

The aims of the TB Risk by Alcohol Consumption (TRAC) study are to estimate the incidence rate of new TB infection among people with HIV (PWH) with prior negative tuberculin skin test (TST) results by level of alcohol use (Aim 1) and to determine the incidence of active TB disease among PWH with prior latent TB infection (LTBI), who received TB preventative therapy (TPT), by level of alcohol use (Aim 2).

TRAC study team celebrating the launch of the PERC study.

As of December 1, 2024, we have successfully concluded TRAC study enrollment with 500 participants. To achieve this goal, we made phone call attempts to 694 prior study participants for Aim 1 screening. We reached 558 participants and invited all of them for screening. Of the 558 screened, we found 522 to be eligible, while 20 people declined consent to participate in the study. Therefore, we enrolled a total of 502 participants into the study, however 2 participants were enrolled in error and were subsequently excluded, leaving the total number enrolled as 500. Self-reported AUDIT-C scores from TRAC baselines visits show 138 (28%) in the no alcohol group, 203 (41%) in the low/moderate alcohol use group, and 158 (32%) in the high-risk alcohol use group. Baseline PEth results of 451 participants show 155 (34%) in the no alcohol use group with PEth levels of <20 ng/ml, 155 (34%) in the no alcohol use group with PEth levels of 20-<200 ng/ml, 155 (34%) in the no alcohol use group with PEth levels of >200 ng/ml.

Of the 500 (217 (43%) females and 283 (57%) males) enrolled with a median age of 42 years, 75 had positive TST results following placement and reading of TST within 72 hours. After excluding 4 participants (2 with prior active TB on chart review, and 2 with no TST result), and including 8 with active TB on chart review but with TST negative results, we found 83 out of 496 (16.7%) had new TB infection/disease. We found no associations with active TB/positive TST at baseline by smoking status, household TB diagnosis, or number of rooms in the household.

We successfully completed 474 6-month follow up phone calls (95% completion rate), 478 12-month in-person visits (96% completion rate), 394 18-month follow-up phone calls (98% completion rate), 221 24-month in-person visits (98% completion rate), and 67 30-month follow-up phone calls (99% completion rate). At the 12- and 24-month visits, we placed PPDs on only those who had negative results at baseline or 12 months. Of the 384 PPDs placed at the 12-month visit, 40 were positive (10% positivity rate). Of the 186 PPDs placed at the 24-month visit, 15 were positive (8% positivity rate). Eight participants were disenrolled from the study and 8 died due to reasons unrelated to study participation.

Aim 2 procedures are in progress. We have completed two rounds of review from TB registries, clinical registries, and medical records in 18 clinics from which participants were recruited in previous studies. We found all records (988 total) included in Aim 2. Of the 988 records reviewed, 28 (2.8%) participants were diagnosed with active TB after receiving INH and 31 (3%) participants were dead. We are investigating the cause of death in these participants. We also found that 109 (11%) participants transferred out of their original clinics.

TRAC study staff (L-R: Ruth, Christine, Adah and Doreen) sorting TRAC DBS cards in preparation for shipment.

Study coordinators including Christine Ngabirano (TRAC study), Naomi Sanyu (TALC study), and Allen Kekibiina (GRAIL study) at a monthly MUST project coordinators’ meeting.

Tuberculosis, Alcohol, and Lung Comorbidities (TALC) Study

In Aim 1 of the TALC study, we will enroll 200 participants in order to investigate the relationship between alcohol use and post-TB lung disease in people with HIV (PWH). As of November 27, the team has screened 131 participants for Aim 1, of which 120 are currently enrolled and have completed the baseline visit. The team is actively completing follow-up visits at the 3-month, 6-month, 9-month, and 12-month time points. The team will begin completing 15-month follow-up visits at the end of December.

In Aim 2, we will qualitatively evaluate factors for tailoring alcohol and smoking interventions in PWH being treated for TB. To this end, we will interview 24 TALC study participants and 12 key stakeholders, including TB providers and other health workers. As of November 27, the team has completed all 12 interviews with key stakeholders and 14 interviews with participants.

The TB HIV Aging in Uganda 50-over-50 (THAU 50/50) sub-study aims to investigate relationships between alcohol use, TB, and aging in PWH. Fifty TALC participants over the age of 50, and 50 new participants (without TB) over the age of 50 will be enrolled. The team has screened 11 new participants, of which 7 are currently enrolled and have completed study procedures. Seven TALC participants over the age of 50 have also completed procedures for the sub-study. Additionally, 3 interviews have been completed for the qualitative aim of the sub-study.

The team has also been busy beginning to disseminate preliminary data from the study. Francis Musinguzi, TALC study RA, presented a poster entitled “Association of Alcohol Use and 6-Minute Walk Distance in People with HIV and Tuberculosis Disease” at the Global Health Collaborative Symposium on November 11. Naomi Sanyu, TALC field coordinator, gave an oral presentation entitled “Drivers of Unhealthy Alcohol Use and Smoking Among People with HIV and TB in Mbarara, Uganda: Patient and Provider Perspectives”, highlighting preliminary results from TALC study qualitative interviews, at the Mbarara University of Science and Technology Annual Research Dissemination Conference (ARDC) on November 15.

TALC RAs Francis Musinguzi and Eunice Kanini at the GHC Symposium.

TALC coordinator Naomi Sanyu presenting at the MUST ARDC.

TALC coordinator Naomi Sanyu receiving a plaque recognizing the TALC study for contributions to research at MUST.

Dr. Kaku So-Armah, Dr. Karsten Lunze, and Lydia Carlson from the BMC study team travelled to Mbarara at the end of November for a study site visit. The team had many fruitful meetings and celebrated study progress, while also looking forward to future studies that may result from this work.

TALC team celebrating the launch of the PERC study. (L-R: Karsten Lunze, Brian Kamugisha, Adrine Mbabazi, Winnie Muyindike, Lydia Carlson, Naomi Sanyu, Kaku So-Armah, Yona Mbalibulha, Eunice Kanini, Francis Musingizi, Justine Muruni, Patrick Agumenaitwe)

Gabapentin to Reduce Alcohol and Improve Viral Load Suppression (GRAIL) Study

GRAIL study enrollment began in November 2023, and as of November 20, 2024 the study has enrolled and randomized 106/300 participants. A total of 608 pre-screenings and 288 in-person screenings have been completed to date. The main reasons for ineligibility include an undetectable HIV viral load (73/93; 78.5%), a negative AUDIT-C score (35/285; 12.3%), and a negative EtG test (100/253; 39.5%). Women comprise 23.6% of the sample. The study team is actively completing follow-up visits with 423 in-person and 370 phone visits completed to date with follow-up rates above 80% for all visits.

The GRAIL study team is preparing for an upcoming DSMB meeting in January 2025.

Dr. Karsten Lunze and Olivia Allison traveled to Mbarara, Uganda for a site visit in November 2024. They were welcomed warmly by the study team and had the opportunity to meet with the new MUST Vice Chancellor, Dr. Pauline Byakika Kibwika.

Collaborators from MUST, UCSF, and BMC met with the Vice Chancellor at MUST, Dr. Pauline Byakika Kibwika.

Members of the study team attended the Annual Research Dissemination Conference hosted by Mbarara University of Science and Technology (MUST), where the GRAIL study was recognized and appreciated by MUST. During this conference, Data Manager Patrick Agumenaitwe presented GRAIL study results on the prevalence of unhealthy alcohol use at baseline study visits. Many thanks to the team at MUST for hosting such a wonderful study site visit!