investigational HIV integrase inhibitor elvitegravir taken once daily continued
to perform as well as twice-daily raltegravir (Isentress) at 96 weeks for treatment-experienced people with
extensive drug resistance, according to data presented last
week at the 19th International AIDS Conference in Washington, DC.
HIV integrase inhibitors prevent the virus from inserting its genetic
material into a host cell, a necessary step for viral replication. The sole approved drug in this class, raltegravir, has
demonstrated long-term efficacy and minimal toxicity, though it has a
relatively low barrier to resistance.
Gilead Sciences next-generation integrase inhibitor elvitegravir is used
with a boosting agent - either ritonavir (Norvir) or Gilead's novel pharmacoenhancer cobicistat - to enable once-daily dosing.
from Whitman-Walker Health presented long term data from a head-to-head phase III randomised controlled trial
comparing 150mg elvitegravir once daily or 400mg raltegravir
twice daily, both in combination with a fully active
boosted protease inhibitor plus a third drug.
145 included 712 treatment-experienced participants in Europe, the US and
Australia; 702 were included in the efficacy analysis.
over 80% were men, 60% were white and the average age was 45 years. The mean baseline
CD4 T-cell count was approximately 220 cells/mm3, with about 45%
having fewer than 200 cells/mm3, and 26% had high viral load
all participants had used - and a
majority had developed resistance to - at least
two antiretroviral drug classes, they were able to construct viable regimens
using a ritonavir-boosted protease inhibitor and an active third agent such as
etravirine (Intelence), maraviroc (Celsentri or Selzentry) or a
nucleoside/nucleotide reverse transcriptase inhibitor. The most frequently used
protease inhibitors were boosted darunavir (Prezista) at nearly 60%, lopinavir/ritonavir
(Kaletra) at 19% and boosted atazanavir (Reyataz) at 16%.
The primary 48-week results, presented at the
International AIDS Society meeting last summer in Rome,
showed that elvitegravir was well-tolerated and non-inferior to raltegravir in
efficacy, with 59% vs 58% of participants in the two arms, respectively,
achieving undetectable viral load.
Blinded comparison continued through 96 weeks and
Study 145 has since moved into an open-label observation phase.
weeks, 41% of elvitegravir recipients and 42% of raltegravir recipients discontinued
treatment. The most common reasons were poor adherence (39 vs 34 participants,
respectively), withdrawal of consent (30 vs 17), loss to follow-up (29 vs 31),
lack of efficacy (17 vs 21), adverse events (11 vs 15) and protocol violations
(11 vs 14).
of elvitegravir and raltegravir continued to be comparable at 96 week, with 48%
and 45%, respectively, having HIV RNA <50 copies/mL in an intent-to-treat 'TLOVR'
analysis. Virological failure (defined as never suppressed, viral rebound or
drug discontinuation due to non-efficacy) was observed in 26% and 29% of
participants, respectively. CD4 cell gains were also similar, at approximately
and raltegravir were well-tolerated overall and few people discontinued due to
side-effects (3% vs 4%, respectively). Grade 2-4 adverse events (68% in both
arms), serious adverse events (20% vs 23%, respectively) and grade 3-4 laboratory
abnormalities (37% vs 42%, respectively) were generally similar. More elvitegravir recipients reported
diarrhoea (13% vs 8%) while more raltegravir recipients had elevated liver
enzymes (approximately 2% vs 6%).
the one-quarter of participants who underwent resistance testing due to
suboptimal response or viral rebound, 7% in both arms showed evidence of
primary integrase resistance mutations.
researchers concluded that at week 96, once-daily
elvitegravir in combination with a fully active boosted protease inhibitor and
another agent in treatment-experienced patients "continues to be
non-inferior to twice-daily raltegravir in efficacy with excellent
has been submitted for approval in Europe and the US for treatment-experienced patients.
Elvitegravir and cobicistat (along
with tenofovir/emtricitabine) are part of a single-tablet regimen known as the
Quad that is under regulatory review for treatment-naive people.