Injectable antiretroviral drugs – a ‘remarkable milestone’
Long-lasting antiretroviral drugs injected monthly present a ‘remarkable milestone’ in treatment options for people living with HIV.
A long-lasting injectable antiretroviral treatment (ART) containing cabotegravir and riviliprine, administered at four- or eight-week intervals, is both as safe and effective at maintaining viral suppression as the same drug combination taken orally.
The results from the LATTE-2 study, an ongoing phase 2b clinical trial, were presented at the International AIDS Conference (IAS) on HIV Science last week in Paris, and published in the Lancet. It is the first study to investigate the safety and efficacy of a long-acting ART for HIV.
In the study, patients were brought to viral suppression with oral ART in an ‘induction phase’, and those who achieved viral suppression were randomly selected to three arms for maintenance therapy. After 96 weeks, viral suppression was maintained in 84% of patients receiving oral treatment, 87% in patients receiving the injectable contraceptive every four weeks, and by 94% in the eight-week group.
Cabotegravir is an investigational integrase inhibitor (INSTI) that has a long half-life, meaning it is active in the body for longer. It is also being considered for use in other clinical trials as a pre-exposure prophylaxis (PrEP).
Rilpivirine is a second-generation non-nucleoside reverse transcriptase inhibitor (NNRTI), developed to counteract mutations associated with HIV drug resistance in this class, and is approved for use only in combination with other antiretroviral drugs.
What are the benefits of long-lasting ART?
People living with HIV can now expect to live a near-normal life expectancy, where they have access to effective antiretroviral treatment, monitoring and support. But the positive benefits of treatment can only be realised when adhered to exactly as prescribed – which for HIV, means taking treatment every day, for life.
A range of factors can influence a person’s ability to stick to a drug-taking regime, so until a vaccine or a cure is found, new treatment delivery options are needed to ensure all patients can maintain high levels of antiretroviral drug concentration in their body, thereby achieving viral suppression and reducing the risk of HIV drug resistance.
In this study, participants revealed they felt free from their illness, with lead study author Joseph Eron Jr., M.D., saying at a press conference: "It's surprising to me - patients at our site that are on the study - how much they appreciate not having to take pills. I think that's something that I really didn't calculate. There's this kind of feeling of freeness from being bound to oral therapy every day."
Mark Boyd, MD, of the University of Adelaide and David Cooper, MBBS, of the University of New South Wales, in an accompanying Lancet commentary said that the long-acting antiretroviral was a “remarkable milestone” for HIV therapeutics – but at some point there will be a “trade-off between the convenience of not having to adhere to oral therapy and the inconvenience and discomfort associated with injectable long-acting ART. It is possible that injectable ART will be more attractive the less one must be injected.”
Some people may find taking oral medication every day more convenient than having to see a healthcare professional to be injected on a monthly basis. Boyd and Cooper continued, “This is compounded by the fact that health-care systems are generally not configured to facilitate regular, recurrent injections in a timely and convenient way to people who are well. Changing this will take innovation, political will, and time.”
Nevertheless, the authors conclude that “long-acting injectables such as the cabotegravir plus rilpivirine regimen might represent the next revolution in HIV therapy by providing an option that circumvents the burden of chronic daily dosing.”