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Oral Combinational Antiretroviral Treatment in HIV-1 Infected Humanized Mice
Published on: October 6, 2022
Cancer therapies in HIV cure research
Thomas A Rasmussen1, Jenny L Anderson, Fiona Wightman
1aThe Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Victoria, Australia bDepartment of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark cDepartment of Infectious Diseases, Alfred Hospital and Monash University, Victoria, Australia.
Purpose Of Review:
This article provides an overview of anticancer therapies in various stages of clinical development as potential interventions to target HIV persistence.
Recent Findings:
Epigenetic drugs developed for cancer have been investigated in vitro, ex vivo and in clinical trials as interventions aimed at reversing HIV latency and depleting the amount of virus that persists on antiretroviral therapy. Treatment with histone deacetylase inhibitors induced HIV expression in patients on antiretroviral therapy but did not reduce the frequency of infected cells. Other interventions that may accelerate the decay of latently infected cells, in the presence or absence of latency-reversing therapy, are now being explored. These include apoptosis-promoting agents, nonhistone deacetylase inhibitor compounds to reverse HIV latency and immunotherapy interventions to enhance antiviral immunity such as immune checkpoint inhibitors and Toll-like receptor agonists.
Summary:
A curative strategy in HIV will likely need to both reduce the amount of virus that persists on antiretroviral therapy and improve anti-HIV immune surveillance. Although we continue to explore advances in the field of oncology including cancer immunotherapy, there are major differences in the risk-benefit assessment between HIV-infected individuals and patients with malignancies. Drug development specifically targeting HIV persistence will be the key to developing effective interventions with an appropriate safety profile.
Insights
Anticancer therapies are being explored to target persistent HIV. While some epigenetic drugs show promise in reversing HIV latency, new strategies like immunotherapy are needed for a functional HIV cure.
Area of Science:
- Oncology and Virology
- Immunotherapy
- Drug Development
Background:
- Antiretroviral therapy (ART) suppresses HIV but does not eliminate persistent virus.
- HIV latency poses a major barrier to curative strategies.
- Cancer therapies offer potential avenues for targeting HIV persistence.
Purpose of the Study:
- To review anticancer therapies in clinical development for targeting HIV persistence.
- To evaluate the efficacy and safety of these repurposed agents.
- To discuss the challenges and future directions for HIV cure research.
Main Methods:
- Review of in vitro, ex vivo, and clinical trial data.
- Analysis of epigenetic drugs, apoptosis-promoting agents, and immunotherapies.
- Comparison of risk-benefit profiles in HIV-infected individuals versus cancer patients.
Main Results:
- Histone deacetylase inhibitors induced HIV expression but did not reduce infected cell frequency.
- Apoptosis-promoting agents, novel latency-reversing compounds, and immunotherapies are under investigation.
- Cancer immunotherapies like immune checkpoint inhibitors and TLR agonists show potential.
Conclusions:
- A curative HIV strategy requires reducing persistent virus and enhancing immune surveillance.
- Repurposing cancer therapies for HIV requires careful risk-benefit assessment.
- Developing novel, safe, and effective interventions targeting HIV persistence is crucial for a cure.
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