UW CRS is Now UW Positive Research!
The University of Washington (UW) CRS 1401 is excited to announce their new name, UW Positive Research. The AIDS Clinical Trials Unit at UW was started in 1987 by Dr. Ann Collier, who led the CRS until September 2020, when Dr. Rachel Bender Ignacio took over as site PI. On May 20, 2022, they hosted a celebration of their participation in HIV/AIDS research over the better part of the last four decades, including the retirement of Dr. Collier this month, as well as their future initiatives under their new name, UW Positive Research.
"We took the question of our name to our Community Advisory Board, and while not unanimous, the overwhelming response we received was excitement to find a more inclusive, less stigmatizing name,” said Dr. Bender Ignacio. “We really owe it to Michael Louella and our CAB for workshopping name ideas that fit the mission of this next decade. The result is a name that we’re proud of, and which reflects the work that we’re doing now in 2022, and we hope will help welcome new folks to join in the efforts to have research that serves everyone in the HIV community. This especially includes folks who are underrepresented in research, including gender-diverse individuals; Black, Brown, and Indigenous people; and younger people with more recent HIV diagnoses. We want folks to know that even though HIV treatment may be just one pill a day for many people now, these treatments come with 40+ years of research, including a tremendous and gracious donation of time, blood, and sometimes other samples donated by many people for whom treatment was not so easy."
The name change to UW Positive Research is a concerted step to facilitate a broader range of research that can positively impact the lives of people living with HIV, including opportunities and an environment that could bring a more diverse group of research participants to their work and a more robust pipeline to train and mentor researchers and staff in clinical trials. UW Positive Research is excited to continue being an ACTG CRS and is enthusiastic about partnering with local investigators and other networks to collaborate on research important to the people in their community.
Please join the ACTG in congratulating Dr. Collier on her retirement and feel free to connect with UW Positive Research!
Introducing the New ACTG Specialty Lab Directors
Over the next several months, the ACTG will highlight the new specialty lab directors. For our first spotlight, we are pleased to share details about the University of California at San Diego (UCSD) Virology Specialty Lab.
The UCSD Virology Specialty Lab team provides a unique combination of basic, translational, and clinical research expertise to support the laboratory needs of the clinical trials and to generate and lead innovative laboratory research within proposed ACTG clinical trials. The team leaders, Drs. Sara Gianella, Antoine Chaillon, and Davey Smith have extensive experience in the design and analysis of clinical studies using virologic assays relevant to the ACTG agenda, including applying many of these assays in human tissues and fluids. Their team provides unique expertise in computational biology and high dimensional data, ranging from quality assurance, to data pre-processing and validation. They also create user-friendly, multifunctional, and customizable pipelines for the transformation of “raw” virologic and genomics data into analytical datasets amenable to higher level analysis in  collaboration with the Statistical and Data Analysis Center (SDAC). Their team continuously strives to enhance the diversity of the biomedical workforce to improve educational experiences, fostering scientific discovery and innovation, enhancing the benefit of research on health-disparate populations, and increasing public trust. Importantly, their team has extensive experience conducting studies involving women, people of transgender experience, and other under-represented populations.
“Having been involved in the ACTG for almost 10 years, it’s an honor to be selected as an official virology specialty lab director,” said Dr. Gianella. “I am especially excited to see a number of women scientists join the laboratory team. One of the things I’m most looking forward to is working with each protocol team to include and adapt laboratory assays and language to be more gender inclusive.”
ACTG and Combination bNAbs
Combination antiretroviral therapy (ART) revolutionized the treatment of HIV and showed efficacy in prevention, but it doesn’t eradicate established infection and worldwide HIV incidence rates have continued to decline slowly. The search for new prevention and treatment interventions remains a high priority. Antibodies are an attractive new treatment modality against HIV because not only can they directly target specific viral epitopes (parts of HIV), but they also have the potential to harness host immune responses and perturb HIV reservoirs (wake up and target sleeping cells with HIV inside). Single-cell antibody cloning methods enabled the identification and subsequent characterization of broadly neutralizing antibodies (bNAbs) with remarkable potency and breadth compared to previously identified anti-HIV neutralizing antibodies. These highly potent new generation bNAbs are a promising new strategy against HIV. Studies have demonstrated that bNAbs can prevent acquisition of bNAb-sensitive viral strains (stop infection). Two recent clinical trials (Gaebler et al and Sneller et al, Nature 202) also demonstrated that a combination of two bNAbs (3BNC117 and 10-1074) can maintain viral suppression after ART is discontinued in individuals harboring sensitive viruses. In addition, early data suggest that bNAbs can affect reservoir size and modify cellular immune responses in people living with HIV. Altogether, these results support continued investigation of this immunologic approach in different clinical scenarios, alone or in combination with other molecules that have been shown to modulate immune responses and perturb HIV-1 persistence (help the immune system clear sleeping HIV from people).
The ACTG plays an important role in this research, and currently two ACTG studies of bNAbs are open for accrual. A5364 aims to expand on the results showing that long-acting bNAbs can maintain suppression in the absence of ART for prolonged periods of time. A5386 is evaluating the combination of two bNAbs with a molecule called N-803 (an IL-15 superagonist), which has been shown in vitro to activate NK and T cells and interfere with HIV latency. These studies will monitor participants closely during a period of ART interruption (stopping HIV treatment) for the return of viremia. In addition, samples from both studies will be carefully analyzed by a broad variety of assays to dissect the underlying mechanism involved in the long-term virologic control, if this is achieved in at least a subset of participants. These studies also provide an opportunity to understand predictors of viral rebound after stopping ART.
In addition to these studies, other protocols are in late development – including studies to evaluate interventions at ART initiation, among people living with HIV who initiated ART during early infection, and of combinations of bNAbs with vaccines and other immune modulators. The ACTG expects that, collectively, these studies will yield important data to further the development of this promising therapeutic approach and guide strategies to overcome some of the implementation challenges, such as pre-existing resistance to the bNAbs and the cost of manufacturing and delivery.
- Written by Marina Caskey, M.D., chair of the HIV Reservoirs and Viral Eradication (Cure) TSG
Publication
The Impact of Rifampin-Resistant Tuberculosis on Child Household Contacts
The A5300/IMPAACT 2003/PHOENix feasibility study team studied household contacts of adult patients with pulmonary tuberculosis (TB) that was resistant to rifampin (an important drug used to treat TB) to determine who needed treatment of active TB and who might benefit from TB preventive treatment. Participants and their child household contacts came from six countries in Africa, Asia, South America, and the Caribbean. About half of the households had children under the age of 15 and children made up nearly a third of all household members. The TB patient was a parent of 30% of children. Only one child had a diagnosis of TB before the study evaluated household members.
This study found that slightly more than half (57%) of the children already had TB but most of them did not have active TB disease. Children in the household were more likely to be TB infected if the adult with TB smoked, was their parent, slept in the same room, or when the children were school-aged and had attended school. Depending on the definitions used, an additional 4.3% (study definitions) to 17.2% (international consensus definitions) of children already had active TB disease. Those with active TB were referred for TB treatment. Prior to the study, only 7% of children had been receiving TB preventive treatment.
High-quality studies need to demonstrate the efficacy of preventive therapy in high-risk household contacts of people with drug-resistant TB before the World Health Organization can make strong unreserved recommendations for its use. This study shows that many children may be at high risk of getting rifampin-resistant TB and may benefit from these studies.
Kim S, et al. High Prevalence of Tuberculosis Infection and Disease in Child Household Contacts of Adults With Rifampin-resistant Tuberculosis. Pediatric Infectious Disease Journal. 2022 May 1;41(5):e194-e202. doi: 10.1097/INF.0000000000003505.
Site Spotlight
Blantyre CRS, Blantyre, Malawi
The Blantyre CRS, which is locally known as Johns Hopkins Research Project in Blantyre, Malawi, is a collaborative research project between the Johns Hopkins University Bloomberg School of Public Health (JHSPH) in Baltimore, Maryland, USA and multiple institutions in the Republic of Malawi. Together with their partners, they strive to contribute meaningfully to improve healthcare practices and policy in the region. The principal investigator, Dr. Taha E. Taha is Professor of Epidemiology at JHSPH and the CRS Leader, Dr. Sufia Dadabhai, is a Johns Hopkins-trained epidemiologist living full-time in Blantyre.
The Blantyre CRS has more than 30 years of quantitative and qualitative research experience dating back to 1989 when the CRS was instituted. It features a multidisciplinary team of more than 170 people working across different DAIDS Network and other networks and non-network protocols. Thirty of these individuals work on ACTG studies in Quality Management, Data and Information Technology, Laboratory, Community Engagement, and Pharmacy departments, including a team of four clinical investigators/principal investigators. The CRS administration building, along with its clinics, laboratory, and pharmacy are located on the grounds of the Queen Elizabeth Central Hospital (the main teaching and referral hospital in the Southern Region). The CRS has also fostered collaborations with surrounding health centers for more than 10 years. In July 2021, the CRS Laboratory received accreditation from the College of American Pathologists (CAP), one of the few in this African region to receive the recognition.
Since becoming an ACTG site in 2005, the Blantyre CRS has conducted 18 ACTG studies, including A5175, A5190, A5199, A5207, A5221, A5263, A5264, A5273, A5274, A5278, A5279, A5282, A5297, A5349, A5362, A5375, A5379, and A5381. Having worked together for 17 years, the ACTG’s teamwork and dedication provides a conducive environment for implementing credible and high-quality research.
The CRS has fostered such a strong community, that sometimes participants from prior studies pass by the clinic just to inquire if there are currently any protocols in which they could participate. Team members in Blantyre report that because people with ailments are the study population for most ACTG protocols, contributing to their clinical care through research, and observing them getting their health back is a joy and makes the work meaningful.
The Blantyre team reports that watching new study coordinators come into their role and grow into their leadership positions, moving from nervous supervisors to confident trailblazers, is one of the most meaningful elements of their work with the ACTG. “They play such a crucial and central role in all stages of a study’s life. It is so important to nurture and empower coordinators and continue to fill the pipeline.”
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