Hello HOPEians,
Please find below the action items from the RF2 meeting on July 6, 2022. If you have any questions about the meeting or action items please reach out to Dr. Nadia Roan and Dr. Lish Ndhlovu.
Updates:
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HIV Natural History Study collaboration / Trevor Crowell – New data from the exposure and timepoint definitions suggests that there are more participants than anticipated (~10) taking spironolactone and some with five or more timepoints. These longitudinal samples may include pre- and post-spironolactone administration. Samples include PBMC but not tissues. They are currently identifying control participants and will finalize the participant selection soon. The MTA agreements for both Susana Valente (University of Florida) and Lish Ndhlovu (Weill Cornell) are undergoing final review and will be sent for signatures soon.
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Sara Gianella Weibel with the Last Gift Cohort gave updates – The Last Gift (NIH P01) was recently renewed until 2027. She also shared modified autopsy procedures (Rapid autopsy → collection biobanking → processing → assays). Their new assays focus on single cell resolution (VENI and VIDI project assays). Shared lessons learned. They found heterogeneous localization of HIV DNA within the CNS and also in the periphery. This variability was participant-specific; however, the higher levels of HIV DNA in the spinal cord stood out and will be investigated further. HIV RNA localization studies are ongoing and so far do not correlate with HIV DNA localization.
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Esper Kallas & Lish Ndhlovu collaboration on tissue studies – Discussed studies for people taking spironolactone, goal is to use paired gut biopsy and peripheral blood analysis of HIV reservoir pre- and post- spironolactone treatment. First, they will look at spironolactone effects on general DNA transcription in HIV negative participants before they complete similar studies in HIV positive participants. The IRB protocol has been submitted at USP and should have a response in approximately 30 days. Initiation of the study can begin soon after IRB approval.
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Susana Valente shared data from Tat degraders that were synthesized (SR-4481 & SR-44863). High concentrations of SR-4483 was used in a preliminary murine study, but titrations will need to be done due to the high toxicity. MTAs are ongoing with Lish Ndhlovu at Weill Cornell and Melanie Ott at UCSF. Susana’s group has tried to validate several additional ERCC3 (XPB) antibodies, since the previously used antibody is longer available. These new antibodies do not work for WB or IP. The Valente lab is also continuing to study the development of viruses resistant to SP. She explained the analysis of virus potentially resistant to SP used alone from the single RhM study from Maurucio Martins. New dCA production is still 2-3 months away. Some of this dCA is earmarked for larger NHP studies.
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Lish shared links to:
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Esper Kallas Oral Presentation for AIDS 2022, August 2, from 10:30-11:30 ET: Shake and bake: Promising strategies for HIV cure
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Viral Infections & Inflammation Workshop 2022 Sep 8- Sep 9 2022
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Actions:
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Sara Gianella – Share ALS patient data and tissue availability with Avi Nath
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Start a new MTA
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Meeting with Sara Lemere, Avi Nath, Sara Weibel, and Lisa Henderson to discuss ALS & Endogenous Retrovirus reactivation in these HIV positive participants.
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Sara Gianella – Collaborate with Avi Nath to mine data for defective proviral sequences
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Sara Gianella – Look for participants who are on spironolactone – inform Susana Valente and Nadia Roan
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Sara Gianella – Share morphine/opioid information on participant cohort with Lish Ndhlovu
Announcements:
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July 13 Guest Speaker: Dr. Mathias Lichterfeld
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The next meeting is on August 3, 2022 – Lisa Henderson will present on assays for measuring defective provirsus and HIV targeting ASOs
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If you are attending the AIDS 2022 in Montreal (July 29-August 2) please let Lish Ndhlovu and Sydney Norman know.
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Register for the HOPE Annual Meeting
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Call for nominations for the HOPE 2022 Awards (Instructions attached)
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Please Acknowledge HOPE & the NIH in any publications or presentations and notify the Program Manager. Here are some examples of what you can include.
“Research reported in this publication was supported by the NIAID of the National Institutes of Health under award number UM1AI164559, with co-funding support from NIDA, NIMH, NHLBI, the NIDDK, and the NINDS. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.”
“This research was supported by NIAID award number UM1AI164559, co-funded by NHLBI, NIDA, NIMH, NINDS, and NIDDK.”