For November 2024, there were 11 updates to TAG’s listing. We’ve also added the country locations for each of the current trials (previously, site locations were only included in the table in our annual Research Toward a Cure and Immune-Based Therapies Pipeline Report).
New Additions
Four new clinical trials were identified in registries:
Researchers in Madrid, Spain are planning to investigate the effects on the tissue HIV reservoir of higher than usual doses of the antiretroviral drugs dolutegravir, maraviroc, and lamivudine. While most studies have concluded that current antiretroviral therapy (ART) regimens completely suppress HIV replication, the registry entry for this new trial states that there’s some evidence of reduced drug concentrations in lymphoid tissue that may be linked to higher levels of HIV RNA. The goal of the protocol is to assess whether ART that can be safely administered at slightly higher doses affects measures of HIV persistence. Previous studies that explored the same question by adding antiretrovirals to standard regimens (treatment intensification) haven’t reported any notable effects on the HIV reservoir. The trial aims to enroll 24 participants but is not yet recruiting.
Several years ago a company named Zion Medical made a variety of implausible claims about the potential efficacy of an HIV drug candidate they named Gammora, a compound supposedly based on protein fragments derived from HIV integrase. A small clinical trial was said to have taken place in Uganda, but — if it did occur — wasn’t approved by appropriate regulatory authorities, as the company eventually admitted in response to an investigation by Bekhisisa. Even more concerningly, substances called Gammora started to be sold as a purported HIV cure, both online and locally. The company issued a release stating they’d entered into an agreement with a Swiss “seller of unlicensed medicines” but the extent of their role in sales is unclear. At least some of the substances sold have turned out to be other potentially dangerous drugs. Representatives from Zion Medical published an abstract rehashing claims about the Uganda trial in 2021, not mentioning that they’d already admitted it was improperly conducted.
Some of the same protagonists now appear to have returned with a different company, Code Pharma, and seemingly a different name for the same compound: Codivir. They’re collaborating with researchers in Brazil to conduct a study in which Codivir is administered alone and then in combination with standard ART. This group recently reported another set of implausible-sounding results at the HIV Glasgow conference (abstract P212), claiming that Gammora (as they were still calling it in the abstract) led to a one-log decline in HIV DNA levels.
TAG will continue to monitor for the presentation of results from the new trial, with the caveat that we’re extremely skeptical regarding the integrity of any data reported by this company. Sales of the compound still appear to be a major focus, as stated on the company website: “Code Pharma has already received emergency approvals from several countries and is preparing for mass production of Gammora in different production sites worldwide based on the received orders.” (TAG has written to the company to ask which countries have granted emergency approvals, because no such reports can be found online).
ViiV Healthcare is recruiting for a new first-in-human clinical trial of a bispecific broadly neutralizing antibody (bNAb) currently codenamed VH4527079. Bispecific means that the antibody has been engineered to block two different parts of HIV that are involved in the process of infecting vulnerable cells (a regular bNAb only has one target). The study will administer VH4527079 to people with HIV on ART and a cohort of participants without HIV.
A collaborative study led by researchers in Denmark and Australia will assess the effects of an immunomodulatory anti-cancer drug, pomalidomide (a safer analog of thalidomide), in people with HIV on ART. The protocol includes an analytical treatment interruption (ATI) to evaluate whether receipt of pomalidomide alters HIV viral load rebound. Pomalidomide has previously shown evidence of efficacy and immune modulation in people with HIV and Kaposi’s sarcoma.
Updates to Enrollment Status
A clinical trial sponsored by CAPRISA in South Africa investigating dual bNAbs in people with HIV is now open for enrollment. The protocol includes CAP256V2LS, a bNAb isolated by South African scientists from an individual with subtype C HIV, and VRC07-523LS, which was identified in samples from an individual with subtype B HIV. The bNAbs will be administered either at the time of ART initiation or a week prior, with an ATI scheduled after around a year of ART to measure any effects on HIV viral load rebound.
Two studies in the listing assessing combinations of interventions are now closed to further enrollment:
- A clinical trial involving two therapeutic vaccines and three bNAbs led by Boris Juelg at the Beth Israel Deaconess Medical Center, taking place at six sites in the United States. Estimated completion date is April 2026.
- A study combining two bNAbs with N-803, a superagonist of the cytokine IL-15 intended to enhance immune responses. Sites are located in New York City and Philadelphia. The principal investigator is Marina Caskey from Rockefeller University, and the estimated completion date is December 2025.
New Links to Study Results
At the recent HIV Glasgow conference Gilead Sciences presented the first results obtained with GS-1966 and GS-1144, experimental therapeutic HIV vaccine candidates licensed from Gritstone Bio. GS-1966 is based on a chimpanzee adenovirus while GS-1144 is a self-amplifying mRNA-lipid nanoparticle, and both include conserved elements of HIV-1 Gag, Pol and Nef in either single (monovalent) or dual (bivalent) forms.
The vaccines were found to be generally safe in people on ART but there was one case of Bell’s palsy leading to discontinuation, which resolved within 14 days. The largest change from baseline to peak T cell responses against HIV was observed among recipients of vaccines containing a bivalent form of the encoded HIV proteins, but the effect of immunization was difficult to distinguish because participants already possessed high levels of pre-existing HIV-specific T cells. Additional detailed analyses of T cell functionality are ongoing. As is often the case with Gilead Sciences, this phase I trial isn’t registered in clinicaltrials.gov or any other online registry, which runs contrary to the company’s oft-repeated claims about prioritizing community engagement with their research (it’s difficult to engage with a trial that’s essentially hidden from public view).
Researchers involved in the RIVER trial in the UK, which investigated early ART initiation plus therapeutic vaccination, published new findings in the Journal of Experimental Medicine. Detailed assessments of the HIV reservoir uncovered evidence that innate immune mechanisms — but not vaccine-induced T cells — appeared to contribute to clearing the virus-infected cells most likely to be visible to the immune system, leaving behind cells containing HIV integrated into regions of the genetic code which are less hospitable to viral reactivation.
Sarah Lefebvre and colleagues have published a social science study looking at reasons for declining the opportunity to participate in an HIV cure-related clinical trial that ultimately wasn’t able to proceed (AMEP-EHVA-T02). The protocol included an ATI, but the ART interruption wasn’t the main reason for lack of interest, rather it was concerns over the logistics and psychological burdens associated with attending frequent study visits.
The final addition this month is a simple replacement of a link to a preprint of a paper with the link to the final published peer-reviewed version in the journal Nature Communications. The research describes a rapid biphasic decline in levels of intact and defective HIV DNA in a study of people who started ART very quickly after HIV acquisition (the results were first presented at the IAS 2023 conference).
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