Almost all HIV-positive people with undetectable
viral load who switched to once-daily raltegravir (Isentress) maintained viral suppression, French researchers
reported at the 14th European AIDS Conference this month in
Brussels. In an effort to facilitate once-daily dosing, Merck is working on a
new tablet that appears less affected by food than the current formulation.
Raltegravir is a
highly effective component of combination antiretroviral therapy (ART)
and is one of the best-tolerated HIV medications, but its standard twice-daily dosing schedule makes
it less convenient than once-daily options.
Fabienne Caby of Hôpital
Pitié-Salpêtrière and colleagues
evaluated whether once-daily raltegravir is able to maintain virological
control when people switch from a fully suppressive combination regimen.
Although pharmacokinetic data
suggest that once-daily raltegravir may provide adequate drug levels, the randomised Phase 3 QDMRK trial showed that 800mg
once-daily raltegravir failed to meet the criteria for non-inferiority to 400mg
twice-daily raltegravir for people starting ART for the first time, with 83 vs
89% achieving undetectable viral load. This was largely driven by poorer
efficacy among people with high baseline viral levels (74 vs 84%, respectively).
But raltegravir may be able to keep HIV under control if viral load is already
observational study enrolled 71 people at 2 centres in Paris who had
undetectable viral load (<50 copies/ml) for at least six months. A majority
(66%) were men, the mean age was 46 years and the median CD4 cell count was
588 cells/mm3. At the time they switched, participants had been on ART
for 14 years on average and had used five antiretroviral 'lines'.
received treatment optimisation that included introduction of 800mg once-daily
raltegravir. Nearly one quarter switched from 400mg twice-daily raltegravir
(taken for an average of eight months), whilst the rest switched from other
drugs and were integrase inhibitor-naive. This was not a randomised trial and
patients were not assigned to a regimen.
addition to once-daily raltegravir, 56% used tenofovir/emtricitabine (the drugs in Truvada) and 18% used
abacavir/lamivudine (the drugs in Kivexa).
Others were on non-standard regimens including 10% taking etravirine (Intelence), 10% taking boosted or
unboosted atazanavir (Reyataz), three
people taking nevirapine (Viramune)
and one taking efavirenz (Sustiva).
The most common reason for switching
was abnormal blood lipid levels (20%), followed by liver toxicity or elevated
bilirubin (15%), lipodystrophy (13%), neuropsychiatric symptoms (10%),
prevention of drug interactions (8%), gastrointestinal symptoms (7%) and
treatment simplification (6%).
At 24 weeks after switching, 99% of
participants still had undetectable viral load, falling to 96% at 48 weeks. The
median CD4 count remained stable at 24 weeks (589 cells/mm3) and
rose to 631 cells/mm3 at 48 weeks.
One person experienced virological
failure at week 24 (defined as any HIV RNA measurement >400 copies/ml or two
measurements >50 copies/ml), joined by two more participants at week 48. In two of
these cases, virological failure was associated with emergence of raltegravir
resistance mutations. All three of these people received raltegravir with two
NRTIs and had a prior history of virological failure on NRTI-containing
regimens; two had pre-existing NRTI resistance mutations.
Among participants with
pharmacokinetic data, 17% (including two of the patients with virological
failure) had raltegravir minimum concentrations below 50 ng/ml, considered the
cut-off for adequate potency.
"In this study, switching to raltegravir [once-daily]
maintains virological suppression over 48 weeks as long as raltegravir is
associated with a fully active backbone," the researchers concluded,
emphasising that this requires clinicians to determine a patient's entire
antiretroviral history and previous genotypic resistance test results.