liv poz mag.qxd - Positive Living BC

Treatment Research
GS
Phase II results for the new GS 9350 booster hold promise
for a four-in-one pill by Nicole Lewis
9350 may look like just a bunch of letters
and numbers, but it could be the next big drug
released to help treat HIV. Gilead Sciences, a US-based
pharmaceutical company, is currently working on an
experimental drug known as GS 9350 (generic name
cobicistat), which boosts the effectiveness of other
HIV drugs. The drug just completed Phase II of
clinical trials and it’s being tested with Gilead’s existing
antiretrovirals with hopes that a four-in-one—or quad—
pill can be developed.
This new product would be used in place of the
current drug, ritonavir (Norvir), manufactured by Abbott
Laboratories. Ritonavir is a protease inhibitor—it
prevents HIV-infected cells from producing new HIV,
therefore limiting the number of doses a person needs to
take of their existing medications. However, ritonavir
can be quite pricey and has side effects such as weight
gain and gastrointestinal problems; it may also cause
drug-resistant HIV, as it always provides anti-HIV activity,
even at a very low dose. These concerns about ritonavir
have driven the development of replacement drugs from
other companies such as Gilead.
The primary function of GS 9350 is to boost the
blood levels of other anti-HIV drugs. For example, the
experimental integrase inhibitor elvitegravir, when taken
with GS 9350, is more effective in blocking the enzymes
that normally allow HIV to integrate into the DNA of an
infected cell.
In 2009, a Phase I study showed promising results
when comparing ritonavir to GS 9350. GS 9350 acted in
a similar way to ritonavir at both 100 mg and 200 mg
doses. Study participants experienced few side effects
from either the daily or twice a day doses.
The Phase I trial also tested how well GS 9350 worked
when combined with the three other medications that
Gilead is hoping to combine into the quad pill: elvitegravir;
emtricitabine (Emtriva), which helps to lower the overall
viral load; and tenofovir (Truvada), which blocks
enzymes that are crucial to viral production. The 150 mg
tablet of GS 9350 boosted levels of elvitegravir in the
MayqJune 2010 living5 23
blood and maintained regular levels of the other two
drugs. Participants experienced few side effects from the
f ixed-dose tablets, with only one case of moderate
increases in liver enzymes.
In recently released data from the Phase II trials,
efavirenz/emtricitabine/tenofovir (Atripla) was compared
to GS 9350. GS 9350 was also studied on its own to get
a better idea of how it will work compared to ritonavir.
The main difference between efavirenz/emtricitabine/
tenofovir and the proposed new quad pill is that the
quad pill would include elvitegravir in the place of
efavirenz (Sustiva). Efavirenz is known to cause central
nervous system side effects such as dizziness. In the
Phase II trial, only 35 percent of participants taking
the GS 9350-boosted combination experienced adverse
events compared to 57 percent of participants taking
efavirenz/emtricitabine/tenofovir. Only 10 percent of
participants taking the quad pill experienced CNS
side effects.
The Phase II results also demonstrated that GS 9350
doesn’t impact the kidneys, which can be a problem with
drugs like GS 9350. Any changes in serum creatinine
levels—which would indicate kidney problems—aren’t
related to the f iltration problems caused by the drug but
to tubular secretion instead.
These strong results hopefully mean that GS 9350 will
progress quickly through Phase III clinical trials, where
any lingering questions around its effect on kidney
function can be answered.
Fingers crossed that GS 9350 is eventually approved,
which would pave the way for a new cost-saving and less
labour-intensive quad pill. Pill burdens for PWAs could
become a thing of the past. 5
Nicole Lewis is a recent graduate of the
University of Victoria Writing Department
and a volunteer with BCPWA’s Treatment
Information Program.