There were 10 changes to the TAG listing in the November update. The completed studies table has also been slightly reorganized to separate the previous “antibodies” category into more specific groupings: anti-α4β7 integrin antibodies, broadly neutralizing antibodies, and intravenous immune globulin (IVIG).
New Additions
Only one new HIV cure-related trial was added since the previous update: an evaluation of interactions between Merck’s MK-4646 and the TB drug (and liver enzyme inducer) rifabutin in 18 HIV-negative participants. The study is due to be completed by the end of the year. MK-4646 is an experimental candidate in a new class of non-nucleoside reverse transcriptase inhibitors (NNRTIs) specifically designed to promote the destruction of HIV-infected cells (categorized as Targeted Activator of Cell Kill or TACK molecules, see prior blog coverage for details). A trial of MK-4646 in people with HIV is ongoing in Moldova and Romania.
Thanks to a poster on Bluesky for alerting us to this study, which wasn’t registered as HIV-related and hence was missed when first posted in clinicaltrials.gov at the end of September.
Updates to Enrollment Status
Four trials have been moved to the completed studies table, along with the addition of a past observational protocol relevant to HIV cure research that was previously missing from our listing (the completed CHRONOS study in Australia).
In three instances, the reason for the move is lack of updates to registry records suggesting the trials are no longer ongoing (in one case, it’s unclear if the protocol ever started). Attempts to ascertain status via emails have been unsuccessful:
- A vedolizumab (anti-α₄β₇ integrin antibody) study at the Ottawa Hospital Research Institute in Canada for which results were presented at CROI in 2019.
- An investigation of the functional cure potential of UB-421 (an antibody inhibitor of HIV binding to CD4 receptors), which was due to be completed in June 2025 but has never been listed as open for enrollment.
- A trial evaluating the anti-HIV reservoir activity of the immunomodulators lenalidomide and adenosylmethionine at the First Affiliated Hospital of Zhejiang University in China, now showing “unknown status” with an estimated completion date of November 2024.
The fourth addition is a therapeutic HIV vaccine trial sponsored by Hookipa Biotech testing arenavírus vectors, which is now listed as “terminated: business decision.”
New Links to Study Results
Since the last update in October, scientific papers have been published related to several studies in the listing:
An article describing the design of AbbVie’s large phase 2 trial of the PD-1 inhibitor budigalimab and the α₄β₇ integrin inhibitor trosunilimab was made available online by the journal Contemporary Clinical Trials on November 9th. The open access paper focuses particularly on how the researchers approached the analytical treatment interruption (ATI) included in the protocol, including drawing on “consensus recommendations, existing interventional studies with ATI, engagement with HIV experts and HIV community members, correspondence with regulatory agencies, phase 1 study results, and the experience of PWH.”
The authors note that the study is unique in international breadth, involving 90 sites across 12 countries. With 160 participants, it’s also the largest HIV cure-related trial including an ATI conducted to date. However, since the registry entry was initially updated at the end of September to “completed,” the record has been amended again to state: “Terminated Company Decision.” No reason is given but it may be cause to temper hopes regarding the results, which are expected to be presented at CROI 2026.
Two new papers describe analyses involving 2000HIV cohort study participants in the Netherlands. In EBioMedicine, researchers report on differences in markers of gene activity between people who naturally control HIV viral load and non-controllers. A study published in Frontiers in Immunology also analyzes spontaneous HIV controllers in the cohort, comparing those who maintain low viral loads with elite controllers who are able to suppress HIV replication to undetectable levels. The study explores a wide range of immunological parameters and identifies commonalities and differences between the groups that may be important for HIV cure research.
Investigators conducting the Last Gift study have published an analysis of potential links between HIV reservoir measures and gut microbiota across five different segments of the gastrointestinal tract. A number of associations were identified that varied by location, but the work is exploratory and statistical significance wasn’t achieved when the results were adjusted for multiple comparisons. The authors note that the possibility of varying interactions along the GI tract should be considered when attempting to design microbiota-based strategies for modulating the HIV reservoir.
The CHRONOS observational study ran from 2015-2018 and initially published findings related to the effect of the circadian rhythm on HIV RNA expression in the Journal of Infectious Diseases in 2021. In a newly published paper in the Journal of Virus Eradication, Jared Stern and colleagues report evidence that acute stress can induce the transcription of HIV RNA by reservoir cells containing HIV DNA. There was no indication of changes in the size of the HIV reservoir.
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