Treatment with Delstrigo was
generally safe and well tolerated in both studies, but there were some notable
differences in side effects between the doravirine-based combination and the comparison
regimens.

In
DRIVE-SHIFT, about 20% of study participants who switched to Delstrigo reported drug-related side
effects, compared with 2% of those who stayed on their baseline regimen. Only
1.6% of Delstrigo recipients stopped
treatment due to side effects.

In
DRIVE-AHEAD, about half as many people taking Delstrigo relative to those on Atripla
reported drug-related adverse events at week 96 (32% vs 65%, respectively) or
discontinued treatment due to adverse events (3% vs 7%). Serious side effects
were rare in both arms (1% or less). The difference was largely due to fewer neuropsychiatric
side effects in the Delstrigo arm including
dizziness (10% vs 38%), sleep disorders (14% vs 28%), abnormal dreams (5% vs
12%), altered cognition (5% vs 9%) and depression/self-injury/suicide (5% vs
7%).

In both
studies, lipid profiles were more favourable for those taking Delstrigo. Among patients starting treatment in DRIVE-AHEAD,
cholesterol and triglyceride levels showed little or no change in the Delstrigo group but increased in the Atripla group. In DRIVE-SHIFT, cholesterol
and triglycerides decreased when people switched to Delstrigo while remaining stable in those who stayed on their baseline
regimen.

Of
note, Merck’s combination pill Delstrigo
contains TDF rather than the newer tenofovir alafenamide (TAF). TAF is
associated with less kidney and bone toxicity, and Gilead Sciences now includes
the new version in its coformulations. Unlike TAF, however, TDF is available as
a generic and can be used by other companies.

While acknowledging that there could be
more kidney-related side effects with Delstrigo, Kumar stressed that we have
more than two decades of experience with TDF use and it is safe for a majority
of people.

“As clinicians we have learned to be
able to understand and recognize the side effects and avoid TDF in patients who
have renal or bone problems or who are at high risk,” she said. “These
years of experience knowing how to manage TDF makes me feel very comfortable
that this is an option for patients who would like to make a switch.”