The single-tablet regimen Eviplera
(rilpivirine/tenofovir/FTC) worked as well as Atripla (efavirenz/tenofovir/FTC) for treatment-naive
people across a range of viral load and CD4 cell counts, researchers reported
Second IDWeek conference last week in San Francisco. Another study found that
switching from a boosted protease inhibitor to Eviplera lowered cholesterol and triglyceride levels
Calvin Cohen from the Community Research Initiative of New England
reported findings from the open-label STaR trial, the first head-to-head
comparison of Eviplera vs Atripla in people starting antiretroviral
therapy (ART) for the first time.
Unlike the earlier ECHO and
THRIVE trials, which compared the same drug combinations taken as
separate pills plus placebos – requiring multiple daily pills with different
food requirements – all participants in STaR took a single tablet once-daily.
The study included 786 participants. More than 90% were men, about
two-thirds were white, one-quarter were black and the median age was 36 years.
At baseline the mean CD4 count was approximately 390 cells/mm3.
Two-thirds started treatment with a viral load at or below 100,000 copies/ml,
about 27% had 100,000 to 500,000 copies/ml and about 7% had above 500,000
copies/ml at baseline.
Overall, both single-tablet regimens produced good virological
suppression: 86% of participants in the Eviplera
arm and 82% in the Atripla arm achieved
undetectable viral load (<50 copies/ml) at 48 weeks in a snapshot analysis.
Virological failure occurred in 8 and 6%, respectively, and CD4 gains were
similar (200 vs 191 cells/mm3).
Cohen reported results from a sub-analysis looking at response rates
according to baseline viral load and CD4 count. Amongst people with a viral load of 100,000
copies/ml or less at baseline, 89% taking Eviplera
and 82% taking Atripla had
an undetectable viral load at week 48, a statistically significant difference.
Among those with a viral load above 100,000 copies/ml, response was lower
overall but similar for the two regimens, 80 vs 82%, respectively.
A similar pattern emerged for CD4 counts. Amongst people with a CD4 count greater
than 200 cells/mm3, response rates were 88% for Eviplera and 83% for Atripla.
Response rates were lower overall for people who started treatment with a CD4 count of 200
cells/mm3 or less but similar for the two regimens, 72 and 71%,
respectively. These differences were not statistically significant.
Turning to adherence as determined by pill counts, people with 95% or
better adherence had high response rates with either Eviplera or Atripla: 90
and 88%, respectively. Response rates dropped among people with less than 95%
adherence, to 75 and 66%, respectively. But neither difference between the two
regimens was statistically significant.
Looking at these factors together, in an analysis that excluded study participants
with missing data, virological response rates were statistically similar for people taking Eviplera and Atripla with all combinations
of baseline viral load, CD4 count and adherence levels. Amongst people with the
least favourable combination – high viral load, low CD4 count and sub-optimal
adherence – only 50% achieved viral suppression with either single-tablet
Turning to virological failure, rilpivirine appeared to fare a bit more
poorly, especially for people with low CD4 counts. In the lower viral load/lower
CD4, strata, two out of ten people (20%) with excellent adherence and three out
of nine (33%) with lower adherence experienced virological failure on Eviplera, compared with none (0%) on Atripla. However, patterns were not
consistent and the number of people experiencing treatment failure was small and affected by missing
data, so differences were not significant.
People with at least 95% adherence reported better
tolerability of both regimens. In particular, highly adherent people taking
Atripla reported fewer efavirenz-associated central nervous
system (CNS) side-effects such as abnormal dreams or depression, but this study could
not determine the direction of cause and effect. Although rilpivirine has been
associated with fewer CNS adverse events than efavirenz in clinical trials,
this sub-group analysis showed that in people with CD4 counts above 200 and
with greater than 95% adherence, the difference in tolerability was much less
noted that this analysis was intended in part to see if rilpivirine is more
vulnerable than efavirenz to resistance and treatment failure if people miss
doses. The findings indicated that although "both drugs suffered from
missed doses," rilpivirine did not appear to do worse.