Monday 28 May 2018

Monthly Once: HIV Drugs on the Horizon


One of the main barriers to HIV drug success is the high level of adherence needed to attain the clinical goals of therapy. For some, the daily task of taking antiretroviral drugs can be overwhelming, particularly when accompanied by emotional or functional issues that can adversely impact the lives—and adherence—of people with living HIV



So profound are these issues that, in the U.S. today, more than 20% of people on antiretroviral therapy are able to maintain an undetectable viral load, the measure for treatment success.
In response, scientists have now begun to explore long-acting drugs, as well as drug delivery systems, that may eventually allow for once-monthly—or even once-quarterly—dosing, either to treat HIV infection or to prevent it.


Long-Lasting Investigational Drugs

In 2013, two long-acting antiretroviral agents were introduced at the 7th annual International AIDS Society (IAS) Conference in Kuala Lumpur. The investigational drugs were both developed as injectable nanosuspensions, wherein tiny crystals of active drug are suspended in liquid, allowing for the slow and steady release of the medication into the system.

The first, cabotegravir (also known as GSK1265744) belongs to a class of drugs called integrase inhibitors, which blocks an enzyme called integrase that HIV needs to multiply. The second, TMC278-LA, is a long-acting formulation of the drug Edurant (ripilvirine) currently used in HIV therapy.

A number of Phase II clinical trials have shown the cabotegravir delivered intramuscularly is generally well tolerated with a mean half-life of between 21 to 50 days (compared to 40 hours following a single, oral dose). Similar studies demonstrated that the drug also ensured sustained drug concentration in rectal and vaginal tissues, suggesting that it could be administered as an effective, long-acting means of pre-exposure prophylaxis (PrEP).

By comparison, a Phase I study showed that TMC278-LA was able to maintain target plasma drug concentrations from 12-26 weeks. The drug also demonstrated promise as PrEP, with stronger concentrations seen in rectal tissues when compared to vaginal tissues.

On-going investigations are planned with the goal of expanding research to Phase II and III clinical trials.


Subdermal Antiretroviral Implants

Scientists at the Oak Crest Institute of Science in Pasadena, California reported developing a matchstick-sized implant that could deliver steady concentrations of antiretroviral medications when implanted beneath the skin.

Similar in design to long-acting contraceptive implants, the device was shown in early research to be able to deliver controlled, sustained release of the drug tenofovir alafenamide (TAF) for up to 40 days.

While research is currently focusing on the device for PrEP, it is suggested that other long-acting agents could eventually be used to provide combination antiretroviral therapy (cART) to people living with HIV.

Future research hopes to open the door to the development of implants that can last for up to a year or more.



To register for the conference STD 2018: https://std-hiv-aids.cmesociety.com/registration

No comments:

Post a Comment