Anti-Cancer Drug Can Expose and Flush Out HIV Hiding in Cells

In a recently published study, international researchers in collaboration have found that the medication Pembrolizumab induces HIV latency reversal in people living with HIV and cancer on antiretroviral therapy. The results appear in the journal Science Translational Medicine. 

The research team found that this medication can reverse the virus latency, which is the ability that the virus has to hide inside cells of people, one of the major barriers to a cure for HIV.

Pembrolizumab is a monoclonal antibody that reverses the exhaustion of the immune system. It is used in the therapy of melanoma. When killer T cells get worn out they express proteins on their surface, one of them called PD1. The monoclonal antibody, referred to as anti-PD-1, works by blocking these exhaustion markers, which allows the killer T cells to regain function and kill cancer. Previous research has shown that PD1 exhaustion markers also allow HIV to go into hiding. 

The study included a cohort of 32 individuals that had cancer and were also living with HIV. The study enrolled participants in the US through the Cancer Immunotherapy Network, based at the Fred Hutchinson Cancer Research Center in Seattle. 

Blood samples were taken before and after treatment with pembrolizumab. The researchers found that the medication modifies the immune response to HIV. 

They observed an increase of a median 1.32 fold in unspliced HIV RNA and a 1.61 fold increase in unspliced RNA:DNA ratio in sorted blood CD4+T cells compared to baseline. Also, they saw an increase of 1.65 fold in plasma HIV RNA. All the data were consistent with anti-PD-1 being able to reverse HIV latency in vivo, and support the rationale of the researchers for combining anti-PD-1 with other interventions to reduce the HIV reservoir. 

The researchers have another clinical trial approved to understand how anti-PD-1 works in people without cancer. 

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Sources:

The Peter Doherty Institute for Infection and Immunity. Study finds cancer immunotherapy treatment can reverse HIV latency. Medical Express. Retrieved from: 

https://medicalxpress.com/news/2022-01-cancer-immunotherapy-treatment-reverse-hiv.html

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https://www.keytrudahcp.com/resources/mechanism-of-action/