Center for Biostatistics in AIDS Research (CBAR): 2025 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, influenza, COVID-19 and mpox 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:
- Dr. Summer Zheng and Ms. Yajing Bao led statistical work on the ACTG A5359 (LATITUDE) study. This study, a phase III, randomized, open-label clinical trial compared monthly treatment with the long-acting injectable cabotegravir and rilpivirine to standard-of-care daily oral ART in people living with HIV (PWH) who had historically been unable to maintain viral suppression. The primary outcome of the study was regimen failure, defined as virologic failure or treatment discontinuation. The study was stopped early for efficacy after a planned interim review. The results, to be published in the New England Journal of Medicine, showed that for PWH with suboptimal adherence, monthly long-acting injectable ART demonstrated superior efficacy in reducing regimen failure over oral standard of care. This pivotal result has led to clinical guideline changes in HIV care.
- ACTG A5418/STOMP was a multinational phase 3, randomized, double-blinded, placebo-controlled clinical trial to evaluate the efficacy of tecovirimat for the treatment of mpox. This NIAID-sponsored trial began in September 2022 as part of the U.S. whole-of-government response to the Clade II mpox outbreak. Drs. Summer Zheng and Pooja T. Saha, and Ms. Caitlyn McCarthy were the statistical leads for this study. The study was closed prematurely after an interim futility analysis showed that tecovirimat was safe but did not improve time to clinical resolution, pain, or viral clearance in adults with Clade II mpox. The results are accepted for publication in the New England Journal of Medicine.
Dr. Minhee Kang and Ms. Triin Umbleja led statistical work on the ACTG A5379 Bee-HIVe trial, a phase 3 randomized trial that evaluated a novel hepatitis B vaccine (HepB-CpG) vaccine versus the conventional HepB-Alum vaccine among people with HIV and prior vaccine non-response. Results published in JAMA showed that 99% achieved HBV seroprotection with 3 doses of HepB-CpG vaccine vs 81% with 3 doses of the conventional vaccine.
- Professor Hughes and Ms. Caitlyn McCarthy led the statistical work on the ACTG A5381 Hakim study that explored virological and drug-resistance outcomes among people living with HIV initiating or switching to tenofovir, lamivudine, and dolutegravir. The observational, cohort study from 6 PEPFAR-supported countries was published in The Lancet HIV and showed high rates of viral suppression in response to tenofovir, lamivudine and dolutegravir therapy in individuals who had suppression before switching support international treatment guidelines for this population. Findings on resistance mutations and tenofovir diphosphate concentrations suggested that incomplete adherence was a key factor in the suboptimal outcomes of people with virological failure at the time of switching treatment.
- Dr. Kristin Baltrusaitis led statistical work on published results from Cohort 2 through Week 24 from the IMPAACT 2017/MOCHA (More Options for Children and Adolescents) study in The Lancet HIV. Additionally, these data informed the European Commission’s authorization of cabotegravir long-acting injections and rilpivirine long-acting injections for HIV treatment, which expanded the adult approval to adolescents aged 12 years and older and weighing at least 35 kg who are virologically suppressed. The IMPAACT 2017/MOCHA study is 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 from this analysis indicate participants:
- experienced high virological suppression with no confirmed virological failures at Week 24
- experienced no drug-related serious adverse events or premature treatment discontinuation due to drug-related adverse events
demonstrating that there were no unanticipated safety concerns at 24 weeks for long-acting injectable cabotegravir and long-acting injectable rilpivirine, given to adolescents every 8 weeks.
- Results were published in The Lancet HIV from P1115, an ongoing Phase I/II, multi-center, proof-of-concept study investigating the effects of early intensive antiretroviral therapy on achieving HIV remission in newborns. Dr. Camlin Tierney and Mr. Bryan S. Nelson provided statistical leadership for this manuscript, reporting four children remained free of detectable HIV for more than one year after pausing their antiretroviral therapy. “This study shows that ART-free remission for 48 weeks or longer is achievable with very early ART in children with in-utero HIV-1, but close monitoring for viral rebound and acute retroviral syndrome during ATI is needed. These findings, observed in resource-constrained countries, exhibit the feasibility of testing at birth and initiating very early ART, show the potential to limit HIV-1 reservoirs for ART-free remission, and inform future remission strategies.”
Dr. Paige Williams is the contact PI for Pediatric HIV/AIDS Cohort Study (PHACS) network, which received a 5-year $40 million grant to support a new study called PHACS RISE, which will be managed by the Department of Biostatistics. Some recent findings published by the PHACS network include:
- Dr. Williams, Biostatistics student Martha Boahene, and Ms. Yanling Huo led a paper based on the PHACS SMARTT study evaluating neurodevelopment in infants of mothers who used antiretroviral (ARV) regimens including integrase strand transfer inhibitors (INSTIs) as compared to other drug classes, published in JAMA Network Open.
- Dr. Kunjal Patel, and HSPH coauthors including Dr. Tzy-Jyun Yao and Ms. Alicia Jaramillo-Underwood investigated growth and immunologic outcomes among young adults with perinatal HIV in the PHACS AMP Up study treated with INSTI-based ARV regimens, published in Clinical Infectious Diseases.
- Dr. Deborah Kacanek and Dr. Williams are co-PIs of the Health Outcomes around Pregnancy and Exposure to HIV/ARVs (HOPE) study, which is closely tied to the PHACS network. A postdoctoral fellow supported by HOPE, Dr. Salome Kuchikhidze, led a paper with Drs. Kacanek, Williams, Patel, Dr. Sean Brummel, Dr. Jeff Eaton, and Ms. Jessica Lee investigating reproductive stage and other factors associated with intimate partner violence, published in AIDS.
- Dr. Kyu Ha Lee and biostatistics colleagues Dr. Brent Coull, Dr. Harrison Reeder, and PhD student Dylan Clark-Boucher utilized data from the PHACS AMP study to illustrate a novel statistical procedure for normalizing differential abundance in microbiome studies, published in BMC Bioinformatics.
