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Gilead drug reduces HIV viral reservoir, says researcher

Treatment with drug was associated with longer viral suppression


An HIV drug in development at Gilead Sciences as part of its programme to develop drug cocktails that could effect a functional cure has generated 'modest' results in its first clinical trial, according to the lead researcher on the project.

Gilead’s toll-like receptor 7 agonist vesatolimod (GS-9620) or a matched placebo was given to 25 HIV-positive subjects in the phase 1b trial, who had shown partial viral suppression prior to starting antiretroviral therapy (ART).

After starting ART, the patients also received bi-weekly doses of either vesatolimod or placebo as an add-on therapy, and then came off therapy while they were monitored for a rebound in HIV levels.

The study did find that vesatolimod was associated with a longer period of viral suppression following treatment interruption compared with placebo.

However, the difference wasn’t very big, at 3.9 weeks for the experimental drug versus 4.1 weeks for control at the most stringent threshold level (>50 HIV copies/mL), but did sneak over the threshold for statistical significance.

At the higher threshold (>200 copies/mL), the difference was five versus four weeks, also a significant difference.

Principal investigator Prof Steven Deeks of the University of California, San Francisco (UCSF) said the study provided the first evidence in people that an immunotherapy “can enhance immune function resulting in both a smaller viral reservoir and an increased time to viral rebound after treatment is interrupted”.

He continued: “The effects are modest, and no one came close to any definition of a cure, but the data suggests real progress might be made when the drug is used in combination with other approaches.”

Vesatolimod is thought to work by alerting the innate immune system – a pathway used as a first line of defence against infection and foreign materials – to the presence of HIV.

Gilead is testing the drug in combination with other drugs including two broadly neutralising antibody (bNAbs) – PGT121 and GS-9721 – and other candidates such as an HIV vaccine candidate developed by Spanish biotech Aelix Therapeutics.

ART has become a highly-effective way to control HIV, allowing people with the virus to achieve life expectancy at or close to normal provided they adhere to treatment closely.

Years ago, it was proposed that aggressive ART regimens might be able to eliminate HIV entirely, but subsequent research showed that there are reservoirs of dormant virus protected from drug therapy in blood, lymph and other tissues.

Progress of sorts in eradicating these viral reservoirs was reported this week when a second patient was deemed cured of HIV after receiving a stem cell transplant for a blood cancer, which involved receiving donated cells with a mutation that prevent the entry of HIV into cells.

Stem cell transplants are high-risk procedures, so the treatment wouldn’t be suitable as a routine therapy for HIV-positive people. Nevertheless, it has encouraged research into therapies that might help patients, such as using gene-editing drugs to splice resistance genes into white blood cells.

Article by
Phil Taylor

11th March 2020

From: Research



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