Center for Biostatistics in AIDS Research (CBAR): 2024 Highlights
The Department of Biostatistics’ Center for Biostatistics in AIDS Research (CBAR), directed by Professor Michael Hughes, has a broad research agenda across infectious diseases including HIV, tuberculosis, viral hepatitis, and influenza, and recently expanded to include COVID-19 and mpox (formerly known as monkeypox) research.
CBAR houses the statistical centers for the international HIV clinical trials networks, the Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections network (ACTG) (led by Professor Hughes) and the International Maternal Pediatric Adolescent Clinical Trials network (IMPAACT) (led by Dr. David Shapiro). CBAR statisticians provided statistical leadership on many studies over the past year. Some highlights include:
- Results presented at the Conference on Retroviruses and Opportunistic Infections (CROI) from the LATITUDE Study, a phase III study to evaluate long-acting antiretroviral therapy in PLWH with a history of challenges to adherence. Dr. Lu Zheng and Ms. Yajing Baolead the statistical analyses reporting long-acting cabotegravir and rilpivirine demonstrated superior efficacy compared to daily oral standard of care in PLWH with adherence challenges.
- Dr. Kristin Baltrusaitis, Mr. Ryan Milligan and Mr. Shawn Ward led statistical work on secondary analysis of the MOCHA study, a phase 1/2, multicenter, open-label, non-comparative dose-finding study exploring the acceptability and tolerability of long-acting injectable cabotegravir or rilpivirine in the first cohort of virologically suppressed adolescents living with HIV. Findings published in Lancet HIV reported high acceptability and tolerability of long-acting cabotegravir or rilpivirine injections in this population and suggests this may be the preferred treatment option for some adolescents living with HIV.
- Results were published in the Annals of Internal Medicine from the SLIM LIVER study, a clinical trial of semaglutide in PLWH with central adiposity, insulin resistance or prediabetes, and fatty liver disease. Mr. Douglas Kitch and Ms. Amy Kantor provided statistical leadership for the pilot study reporting clinically significant liver fat reductions over 24 weeks
- 29% of participants had complete resolution of Metabolic dysfunction–associated steatotic liver disease
- 58% had a relative reduction in liver fat of at least 30%.
- Significant improvements in anthropometric measurements, glucose regulation markers, and triglyceride concentrations were also observed.
- Dr. Michael Hughes and Ms. Caitlyn McCarthy led the statistical analyses exploring the effectiveness of double-dose dolutegravir in PLWH receiving rifampin-based tuberculosis treatment. The observational, cohort study of predominantly ART-naive people with TB/HIV from 6 countries published in Clinical Infectious Diseases reported the treatment was feasible, well tolerated, and achieved high viral suppression rates.
- Results published in the Clinical Infectious Diseases from the IMPAACT 2010/VESTED Study Team, with statistical analyses lead by Dr. Sean Brummel and Ms. Lauren Ziemba reported findings supportive of guidelines recommending dolutegravir (DTG) -based ART for women starting ART during pregnancy, concluding “antepartum weight gain on DTG regimens was protective against adverse pregnancy outcomes associated with insufficient weight gain.”
Dr. Paige Williams is a principal investigator for the Pediatric HIV/AIDS Cohort Study (PHACS) network.
- The PHACS SMARTT study co-chaired by Dr. Williams, together with Mr. George Sawyer and Dr. Kunjal Patel, has continued to publish findings on the effect of maternal ARV use in pregnancy on adverse pregnancy outcomes, such as birth defects and birth outcomes with newer ARVs such as bictegravir.
- With data collected in the PHACS AMP study, Dr. Denise Jacobson together with Drs. Sean Brummel and Kunjal Patel investigated bone accrual trajectories in children with perinatal HIV. Two separate papers based on the PHACS AMP study were published on mitochondrial-associated measures in children with perinatal HIV and their relation with insulin resistance and clinical diagnoses, including Drs. Denise Jacobson, Deborah Kacanek, and Tzy-Jyun Yao along with Ms. Wendy Yu and Mr. Zhongli Zhang.
- Dr. Deborah Kacanek and Dr. Williams are co-PIs of the Health Outcomes around Pregnancy and Exposure to HIV/ARVs (HOPE) study. Dr. Kacanek led a publication of the HOPE study design together with PHACS statisticians and epidemiologists, Drs. Tzy-Jyun Yao, Kunjal Patel, Denise Jacobson, and Paige Williams along with Ms. Jessica Lee, which was published in BMJ Open.
- The PHACS network has an active program of mentoring early-stage investigators (ESIs), including support for statistical analysis and epidemiologic methods, which has resulted in 38 first author papers led by ESIs between 2020-2024.
Results of a mechanistic substudy from the REPRIEVE clinical trial, a global cardiovascular disease prevention trial in people living with HIV (PLWH), were reported in JAMA Cardiology. The substudy aimed to investigate the effects of pitavastatin on noncalcified coronary artery plaque, measured by coronary computed tomography angiography , as well as its effects on inflammatory biomarkers as potential mechanisms for prevention of major adverse cardiovascular events. Findings indicate that for PLWH at low to moderate CVD risk, 24 months of pitavastatin reduced noncalcified plaque volume and progression, and markers of lipid oxidation and arterial inflammation. The statistical center is led by Dr. Heather Ribaudo working with Ms. Triin Umbleja, Mr. Jorge Leon-Cruz, Ms. Amy Kantor, and others within CBAR.
Follow-up of participants was completed in the ACTIV-2 adaptive platform trial designed to evaluate multiple outpatient therapeutics for people with COVID-19. The large statistical team is led by Professor Hughes, Dr. Carlee Moser, Dr. Mark Giganti and Mr. Justin Ritz. For the phase 3 trial of SAB-185, participants were randomized to open-label SAB-185 or casirivimab/imdevimab administered once by intravenous infusion. Results published in the Journal of Infectious Disease, led by Dr. Carlee Moser, Mr. Justin Ritz and Dr. Mark Giganti, showed that in addition to an acceptable safety profile, for those infected with the Omicron variant, time to resolution of symptoms was shorter (18 days versus greater than 25 days) with SAB-185.
