No new HIV cure-related trials or studies were added to the clinicaltrials.gov registry over the past month. A total of seven updates were made to TAG’s listing:
A clinical trial in Barcelona, Spain investigating the effects of the drug dasatinib on HIV persistence and inflammation is now open for enrollment. Dasatinib is a tyrosine kinase inhibitor approved for the treatment of certain forms of chronic myelogenous leukemia and acute lymphoblastic leukemia. Studies in people with HIV receiving the drug to treat cancer have reported an association with a smaller HIV reservoir size and reduced capacity to reactivate viable HIV from latently infected cells. Proposed mechanisms include enhancing the activity of an innate antiviral enzyme, SAMHD1 (by preventing phosphorylation of the enzyme), immunomodulatory effects on natural killer cells and T cells, and possibly also a reduction in the proliferation of HIV-infected CD4 T cells. Two poster presentations at the XIV Congreso Nacional GeSIDA last month reported additional evidence that the use of tyrosine kinase inhibitors in people with HIV and cancers is associated with reductions in the size of the viral reservoir and potential enhancement of the cell-killing potential of natural killer cells and CD8 T cells (see abstracts PT-07 and PT-08).
An ongoing clinical trial sponsored by Gilead Sciences in the FRESH cohort of young women in South Africa is now closed to enrollment. The study is investigating whether a combination of two broadly neutralizing antibodies (bNAbs) and vesatolimod, a toll-like receptor 7 agonist, can enhance viral load control during an analytical treatment interruption (ATI) in participants who started antiretroviral therapy (ART) very early after HIV acquisition.
A phase IIa study of the long-acting broadly neutralizing antibody GSK3810109A (formerly named N6-LS) is now completed. The focus of the research was more on potential use as a treatment rather than cure. The most recent presentation of results was at the European AIDS Clinical Society (EACS) conference, where researchers reported a good safety profile and favorable pharmacokinetics. A phase IIb trial is planned.
Two observational studies sponsored by Radboud University in the Netherlands have also been completed. The 2000HIV and 2000HIVTrained studies used new multi-omics approaches to investigate biological pathways and biomarkers potentially linked to a variety of variables including non-AIDS comorbidities, elite control, and the latent viral reservoir in a large cohort of people with HIV. Two abstracts reporting results were presented at CROI earlier this year (see abstracts 313 and 314).
Links to newly published results were added for two trials in the listing:
The IMPAACT P1115 study assessing the potential for HIV remission in infants treated very soon after birth described results in a paper in the Lancet HIV (access free with registration), following a presentation by principal investigator Deborah Persaud at CROI 2022. A subset of ten out of 54 infants studied became HIV antibody negative and had non-detectable HIV-1 DNA after two years, which represent the criteria for considering an ATI. The researchers note that overall HIV suppression rates were not optimal and improved pediatric ART regimens are still needed. The second iteration of IMPAACT P1115 is now testing regimens including an integrase inhibitor (raltegravir) and a broadly neutralizing antibody (VRC-01).
Scientists affiliated with the ACTG published a paper in the journal AIDS presenting results from a phase I/IIa study of an HIV-1 Gag conserved element DNA vaccine in people on ART. The aim is to induce or boost T cell responses targeting parts of the HIV Gag protein that appear constrained in their ability mutate, and are thus typically conserved among HIV variants. The vaccine, combined with vaccine containing the full Gag protein, induced new T cell responses to conserved elements in a little less than half of the 18 recipients (44.4%). Whether these T cell responses can effectively kill HIV-infected cells is not yet known. A paper published in Science yesterday reported that the ability of HIV vaccine-induced T cells to kill HIV-infected cells may be impaired by poor avidity - a measure of the ability of T cells to efficiently recognize and engage with low amounts of viral fragments displayed (like alarm signals) by cells infected with HIV.
Lastly we made an adjustment to the current clinical trials table this month, creating a separate category specifically for broadly neutralizing antibodies rather than using a general category of just “antibodies.” Other antibodies are now categorized based on mechanism of action e.g. anti-α₄β₇ integrin antibodies, CD4 attachment inhibitors.
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