While treating an HIV-infected patient for lung cancer, a cancer drug caused a “drastic and persistent decrease” in viral reservoirs, raising hopes of a new HIV treatment.

Doctors at the Pitie-Salpetriere Hospital in Paris may have found a cancer therapy that is also a highly effective human immunodeficiency virus (HIV) treatment. In a letter written to Annals of Oncology, the group explained that a cancer drug, nivolumab, a drug sold by Bristol Myers Squibb under the tradename Opdivo, dramatically reduced HIV reservoirs.

The patient was being treated for lung cancer but had previously been infected with the virus. As the doctors expected, the drug re-activated HIV, as well as CD8+ T cells against the virus, leading to a sustained decrease in the amount of HIV. But, they remain cautious, as this is the first patient where a decrease in HIV was observed.

HIV infects and integrates itself into the genome of CD4+ T cells and impairs their function. This causes the immune system to deteriorate until it can no longer fight infection and disease. The individual is now at risk of opportunistic infections, cancers and developing acquired immunodeficiency syndrome (AIDS). With more than 36 million people affected by HIV/AIDS worldwide, something needs to be done.

Latent HIV reservoirs are established during the earliest stage of HIV infection. When a latently infected cell is reactivated, it begins to produce HIV again. This re-activation is blocked by cellular molecules called immune checkpoints like programmed death-1 (PD-1), which can also block CD4+ T cells from fighting the virus.

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PD-1 ligands on tumor cells turn off T-cells by binding to the PD-1 receptor. Therefore, PD-1 inhibitors have been developed to fight cancer, but could also prove to be an effective HIV treatment.

Nivolumab is a PD-1 inhibitor that was proposed to re-activate latent HIV-infected CD4+ T cells, making them visible to the immune system. Drugs that inhibit immune checkpoints like PD-1 are known in the cancer field to efficiently restore immune defences. The group in Paris has now demonstrated that nivolumab could bring dormant HIV-infected cells back to life, helping the immune system to bring the HIV infection under control.

Next, the group must look into the safety of using these drugs in immunocompromised individuals like HIV patients and whether there are biomarkers that can indicate which patients are likely to respond to the treatment. Finally, nivolumab will be tested in a larger group of patients to see whether the results seen in this latest patient can be replicated.

It is also worth considering both the pros and cons of repurposing drugs. Although a repurposed drug has already proved itself to be safe and could be cheaper to bring to the market, many fail for a number of reasons including a lack of efficacy in their new application.

The field is bulging with biotech and pharma companies searching for a new and effective HIV treatment or even a cure. Abivax recently enjoyed positive Phase IIa results, while Sanofi has developed a ‘super-antibody’ that can kill 99% of HIV strains. Elsewhere, a young Berlin-based biotech, Immunologik, is using crowdfunding to support its research, targeting host cell proteins that are crucial to the HIV infection.


Images – Liya Graphics / shutterstock.com; The Pharmaceutical Journal

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