Cancer drug shows promise in HIV cure study in humanized mice

A widely used cancer drug can be used to deplete HIV latently infected cells and delay viral rebound in humanized mice, according to a study from a team of researchers in Australia.

In the study, venetoclax – which is currently used to treat certain blood cancers – delayed viral rebound in a pre-clinical model of latent HIV infection and depleted HIV DNA ex vivo in CD4+ T-cells from people living with HIV who were on antiretroviral therapy.

Presented by Philip Arandjelovic of the Walter and Eliza Hall Institute of Medical Research in Melbourne, the study was a collaboration with the Doherty Institute, a joint venture of the University of Melbourne and Royal Melbourne Hospital, also based in Melbourne.

The team assessed whether inhibiting host pro-survival proteins with venetoclax could preferentially prime latent cells to die and clear the viral reservoir.

In the CD4+ T cells treated ex vivo in a dose-dependent manner, intact DNA displayed a median-fold change of 0.58x with 100 nanomolars of venetoclax.

The drug-induced higher rates of death in naïve and central memory T-cells compared to other T-cell subsets, and cells with higher expression of transcripts of pro-apoptotic BH3-only proteins were overrepresented in the venetoclax-sensitive population.

In the humanized mouse model, researchers evaluated time to viral rebound following cessation of antiretroviral therapy.

When dosed on weekdays for six weeks, venetoclax significantly delayed viral rebound after cessation of antiretroviral therapy.

When combined with the MCL1 inhibitor S63845 and dosed on weekdays for three weeks, the combination achieved a longer delay in viral rebound compared to either intervention alone; the median time to viral rebound was three weeks.

“These are very encouraging results,” Lewin, a member of the study team, said. “It’s exciting that venetoclax will soon be tested in a clinical trial in Australia and Denmark as a potential pathway to an HIV cure.”

Abstract and session: Venetoclax, alone and in combination with the BH3-mimetic S63845, depletes HIV-1 latently infected cells and delays rebound in humanized mice, Track A late-breaker session (5735, Track A)

“This is an incredibly exciting time in HIV research, and the studies at IAS 2023 reflect that,” Sharon Lewin, IAS President, IAS 2023 International Chair and Director of the Peter Doherty Institute for Infection and Immunity at the University of Melbourne in Australia said.

“The science presented at this conference will guide rollout of game-changing prevention tools like long-acting PrEP, shed light on how to reduce the impact of mpox and COVID-19 on people living with HIV, and identify new approaches to achieve an HIV Cure.”

Hosted by IAS – the International AIDS Society – IAS 2023 will take place in Brisbane, Australia, as well as virtually from 23 to 26 July.

The conference will bring together thousands of scientists, policy makers and advocates to examine the latest advances in HIV research and forge a more equitable and innovative HIV response.

Today’s scientific highlights press conference featured seven studies that were selected from among hundreds of abstracts being presented at IAS 2023.

About the International AIDS Society

IAS – the International AIDS Society – convenes, educates and advocates for a world in which HIV no longer presents a threat to public health and individual well-being. After the emergence of HIV and AIDS, concerned scientists created the IAS to bring together experts from across the world and disciplines to promote a concerted HIV response.

Today, the IAS and its members unite scientists, policy makers and activists to galvanize the scientific response, build global solidarity and enhance human dignity for all those living with and affected by HIV.

The IAS also hosts the world’s most prestigious HIV conferences: the International AIDS Conference, the IAS Conference on HIV Science and the HIV Research for Prevention Conference. For more information, visit www.iasociety.org.

About the IAS Conference on HIV Science

The IAS Conference on HIV Science is the world’s most influential meeting on HIV research and its applications. This biennial conference presents the critical advances in basic, clinical and operational HIV research that move science into policy and practice.

Through its open and inclusive programme, the meeting sets the gold standard of HIV science, featuring highly diverse and cutting-edge research. The 12th IAS Conference on HIV Science – known as IAS 2023 – will take place in Brisbane, Australia, from 23 to 26 July 2023. More than 5,000 scientists, clinicians, public health experts, community leaders and people living with HIV are expected to attend IAS 2023. For more information, please visit www.iasociety.org/conferences/IAS2023.