Researchers at Queen Mary University of London have led the clinical development of the first non-integrase stand-transfer inhibitor (INSTI) single tablet treatment for HIV, amongst growing concern for the potential of widespread INSTI-resistance in resource limited settings. The results of the landmark phase 3 trial, published in The Lancet, show that the once-daily, single tablet combination of doravirine with islatravir is effective and safe treatment for HIV.
People living with HIV can live long, healthy lives, but this requires a lifetime of treatment. All of the currently recommended HIV treatment regimens include an integrase strand-transfer inhibitor (INSTI) - a drug that blocks the integration of the virus into the genome. Because of their high efficacy, high barrier to resistance, favorable tolerability, and low liability for drug-drug interactions, they are the first-line HIV treatment across international guidelines and are being rolled out widely across low-income regions.
However, emerging public health surveillance data from these WHO regions shows evidence of emerging resistance to INSTIs, raising concerns of the potential for widespread INSTI resistance, as well as the urgent need for non-integrase HIV treatments.
The landmark study, led by Professor Chloe Orkin, Director of the SHARE Collaborative at Queen Mary University of London, shows that the new combination of doravirine plus islatravir has similar efficacy and safety to the integrase inhibitors. The study recruited far higher-than-usual numbers of women, older people, and racially minoritised adults for the trial - groups that are chronically under-represented in randomised trials for HIV treatments.
Professor Orkin also led the clinical development of first ever long-acting injectable HIV treatment, Cabotegravir and Rilipivirine.
Professor Orkin said: "This is an important moment in the development of HIV treatments. INSTI-resistance could have huge consequences for the treatment of HIV and the ability of people living with HIV to live long, healthy lives, so novel treatments - like doravirine/islatravir are needed.
"Also, islatravir is a drug with long-acting potential that is being evaluated as the first ever weekly tablet to treat HIV at Barts Health NHS Trust and internationally, so its safety and efficacy as a daily pill is an important step on the road to more long-acting formulations being developed for HIV," Professor Orkin added.
