Featured news from NHIVNA
HIV-related news from NAM
Once-daily raltegravir works as well as twice-daily for initial HIV treatment
Liz Highleyman, 2016-07-26 10:00:00
A new formulation of the integrase inhibitor
raltegravir (Isentress) taken once
daily suppressed HIV viral load as well as the older formulation taken twice a
day in people being treated for the first time, according to findings from the
ONCEMRK study presented in a late-breaker session at the 21st International AIDS Conference (AIDS 2016) last week in Durban, South Africa.
Integrase inhibitors are
a potent and well tolerated class of antiretrovirals. The first one to be
approved, Merck's raltegravir, is considered safe and effective, but its
twice-daily dosing schedule is a disadvantage in an era of once-daily
In the previous QDMRK
dosing of the original approved formulation of raltegravir was found to be less effective than twice-daily dosing for initial HIV suppression in previously untreated
patients, though it worked well as maintenance therapy for people who had already achieved undetectable viral
At AIDS 2016 Pedro Cahn of Fundacion Huesped
in Buenos Aires presented findings from ONCEMRK, a phase
3 randomised controlled trial testing an investigational reformulated version
of raltegravir designed to maintain adequate concentrations in the body over a
This analysis included 797 previously
untreated participants in Europe, North America, Asia, Latin America and Africa.
Most (85%) were men, a majority were white, the mean age was about 34 years and
3% were co-infected with hepatitis B or C. The mean CD4 T-cell count was approximately
400 cells/mm3 and the mean plasma HIV RNA level was 4.6 log10 copies/ml
(about 40,000 copies/ml), though 28% had a high
viral load above 100,000 copies/ml and about 5% had more than 500,000 copies/ml.
were randomly assigned to receive the older raltegravir formulation at 400mg
twice daily or the new formulation at 1200mg once daily (two 600mg tablets taken
at the same time), both with tenofovir/emtricitabine (the drugs in Truvada) for up to 96 weeks.
Dr Cahn noted that the 600mg tablet is only slightly larger than the 400mg
Cahn presented 48-week results showing that 1200mg once-daily raltegravir was
as effective as 400mg twice-daily dosing. Viral load declined rapidly in both
treatment arms. At 48 weeks 88.9% in the once-daily group and 88.3% in the
twice-daily group had HIV RNA <40 copies/ml. Using the more common <50
copies/ml cut-off, response rates were 89.9% and 90.2%, respectively.
response did not differ according to baseline viral load. Among people who
started with a high viral load, 86.7% in
the once-daily arm and 83.8% in the twice-daily arm had HIV RNA <40
copies/ml at 48 weeks.
cell gains were also similar, about 230 cells/mm3 in both groups.
7% of participants in both arms experienced virological non-response or viral
rebound (protocol-defined virological failure). Five people in the once-daily
arm had evidence of drug resistance, including four with raltegravir
small differences between the two arms showed that once-daily raltegravir dosing
was non-inferior to the twice-daily regimen.
raltegravir was generally safe and well tolerated, with both dose regimens
having similar safety profiles. More than 90% of participants completed 48
weeks of treatment; 7.7% in the once-daily arm and 8.9% in the twice-daily arm
and twice-daily dosing were associated with comparable rates of drug-related
adverse events (25% vs 26%, respectively) and laboratory abnormalities. Drug-related
serious adverse events (0.2% vs 0.8%, respectively) and discontinuations due to
adverse events (0.8% vs 2.3%) were less common in the once-daily arm, though
quite low overall. Dr Cahn noted that side effects were
mainly gastrointestinal, with no neurological symptoms occurring in more than
2% of participants.
"Reformulated once-daily raltegravir may offer a new potent, well
tolerated and convenient option for initial treatment of HIV infection,"
the investigators concluded.
instructions for the older twice-daily raltegravir formulation call for
doubling the dose when co-administered with rifampin, an antibacterial drug
used to treat tuberculosis. In response to a question, Dr Cahn said he would
"be careful" using 1200mg once-daily raltegravir with rifampin until
pharmacokinetic studies are completed.
Based on these findings, the
European Medicines Agency has accepted the once-daily formulation of
raltegravir for review, and Merck plans to request US Food and Drug
Administration approval later this
year, the company indicated in a press release.