AIDS and Cancer Specimen Resource (ACSR)

Sylvia Silver1, Jeffrey Bethony1, Paige Bracci2, Ashokkumar A. Patel3, Mostafa Nokta4, Michael Ittmann5, Lisa Rimsza6, Johann Schneider7 and Michael McGrath2 1 George Washington University, Washington, DC, US 2 University of California, San Francisco, CA, US 3 Biodata Solutions, Cleveland, OH, US 4 Office of HIV/AIDS Malignancies, National Cancer Institute, National Institutes of Health, Bethesda, MD, US 5 Baylor College of Medicine, Houston, TX, US 6 Mayo Clinic, Scottsdale, AZ, US 7 Stellenbosch University and National Health Laboratory Service, Cape Town, ZA Corresponding author: Jeffrey Bethony (jbethony@gwu.edu)

Keywords: Biobanking; biological samples; HIV; AIDS; AIDS-related malignancies; non-AIDS-related malignancies; Tissue Microarrays Funding statement: The U.S. NIH National Cancer Institute has funded the ACSR since 1994. The present award is UM1CA181255.

Project description
The ACSR includes biospecimens from persons with HIV/AIDS who have been diagnosed with a wide spectrum of HIV/AIDS-related diseases and conditions, particularly malignancies. The ACSR's mission is to acquire, store, and equitably distribute these samples and associated clinical data to investigators conducting HIV/AIDS-related research. The current inventory includes several large well-annotated special collections, including domestic and sub-Saharan African HIV-related clinical epidemiology studies, AIDS Malignancy Consortium (AMC) clinical trials, and multisite autopsies. In addition, cancer-specific and multisite autopsy tissue microarrays (TMAs) have been created to support screening studies. Ongoing biospecimen science projects assess the "fit for purpose" of various archival samples, including protein and nucleic acid derivatives, for the evolving needs of HIV/AIDS and the HIV/AIDS malignancy research.

Classification (2)
Biological samples and clinical data.
Shipping temperature from storage to research use • -56°C (dry ice) for frozen tissue and whole blood derivatives stored at -70°C (e.g., PBMCs, sera, and plasma). • -190°C (Liquid Nitrogen) for snap frozen tissue and whole blood derivatives already stored in LN2.

Source of associated data
Level of sample annotation varies widely due to the variety of sources from which samples are/were acquired and when they were acquired. At a minimum, HIV status, date of collection, age at collection, race, sex, ethnicity, specimen diagnosis (tissue) and/or clinical diagnosis (fluids), and organ site, are captured. Additional data may include CD4 count, viral load, and highly active antiretroviral therapy (HAART). Special collections i.e. samples from clinical trials and epidemiological studies are extensively annotated with demographic, behavioral/lifestyle, clinical and outcome data available.
• Medical records and pathology reports. A list of associated data can be found in the Inventory Explorer (https://acsr.ucsf.edu/inventory-explorer).

Silver et al: AIDS and Cancer Specimen Resource (ACSR)
Art. 12, page 3 of 5 • Clinical trial data from closed AMC clinical trials.

Ethics Statement
Each Regional Biospecimen Repository of the ACSR has local institutional IRB approval. Researchers approved to use specimens must submit an approved IRB from their institution. ACSR specimens are intended to be stored indefinitely. The South African Biorepository has local or national IRB approval.

Constraints
The ACSR inventory has collected material for over 25 years and reflects the research topics, trends, and preservation methods at the time of collection.

Bioresource name
The AIDS and Cancer Specimen Resource (ACSR)

Anatomical site
Any.

Disease status of patients/source
• HIV positive; • HIV positive with malignancy; • HIV negative with malignancy; • HIV positive with no malignancy; • HIV negative with no malignancy.

Clinical characteristics of patients/source
• HIV+ pediatric and adults cases of males and females with or without malignancy from pre-and post-HAART.

Access criteria
The ACSR solicits standard Letters of Intent (LOI) and Feasibility (Short) Form LOIs from investigators throughout the year. LOIs that are completed in accordance with the described requirements (see website (https:// acsr.ucsf.edu) will be submitted for scientific review. Confirmation of receipt and submission of an LOI for scientific review is documented via an email that includes an LOI tracking number to be referenced in all future correspondence. Investigators are encouraged to submit an inquiry specifying the type and quantity of biospecimens that they are interested in obtaining from the ACSR -this inquiry can be done from the ACSR website. The RBRs will work with the investigator and the ACSR to verify the availability of the requested biospecimens and further assist the investigator through the LOI process, which includes assistance in identifying a SSA collaborator for requests of biospecimens from our SSAB. Once the biospecimen type and quantity have been confirmed in the ACSR inventory, the investigator will be directed to submit an LOI. The LOI should succinctly describe the research plan including justification of the number and type of biospecimens requested. The Feasibility (Short) Form LOI is designed for pilot studies that require a minimal number of biospecimens, e.g., for test development, quality control, and/or to generate preliminary data/research. The Feasibility (Short) Form LOI allows a researcher to request up to 20 biospecimens on a one-time basis for a particular study. (https://acsr.ucsf.edu/wp-content/uploads/2018/03/ ACSR_Feasibility_Form-02132018.pdf).
The Standard Form LOI is used for all other requests and requires a more detailed research plan, including a power/sample size and statistical analysis section. The Standard Form LOI is reviewed and scored by members of an independent Research Evaluation and Decision Panel (REDP), which is composed of individuals with the relevant scientific expertise. The review and score are used by the ACSR Executive Committee to make the final decision for the request for biospecimens and associated data. If the ACSR does not have the number and/or types of samples that meet the investigator's research needs, every effort will be made to identify an appropriate resource. For each LOI, an ACSR representative assists with the distribution of biospecimens and/ or other inquiries including scientific/technical issues. ((https://acsr.ucsf.edu/wp-content/uploads/2018/03/ ACSR-LOI_Standard_Form_02132018.pdf)).
Letters of Support (LOS) to document the ACSR's commitment to work with an investigator to provide the necessary biospecimens required for a proposed research project also can be provided. These letters can be included for a National Institutes of Health (USA) or other grant applications as needed.
IRB approval and completion of a Material/Data Use Agreement (MTA/DUA) must be received by the ACSR before disbursement of any biospecimens. Investigators who fail to complete the MTA/DUA and IRB approval documentation within six months of receiving their letter of approval will have the approval voided, making those biospecimens available to other investigators.

(4) Reuse potential
The ACSR provides high-quality specimens from HIV-infected individuals with or at substantial risk for cancer, with associated clinical data, at no cost to eligible researchers. Requests are handled on an ad hoc basis through an application process described above. There is an expectation that researchers should share data/research findings with the ACSR, addressing the principle of data/information sharing. Researchers should also provide feedback on the quality of the specimens that they received/used in their research, as well as acknowledge the ACSR as the source of the specimens data. https://acsr.ucsf.edu/request-specimens/