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
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