People who switch away from their initial
antiretroviral therapy (ART) regimen when their viral load is undetectable may
have a higher likelihood of subsequent virological failure, researchers
reported at the 20th International AIDS Conference (AIDS 2014) last week, in Melbourne. However, the association varied across
groups and the researchers suggested their findings may reflect issues such as
adherence or treatment changes due to pregnancy.
Experts recommend starting HIV treatment with a maximally
potent combination antiretroviral regimen, especially for people with high
viral load. But even in the modern ART era many people wish to switch regimens for
the sake of better tolerability or simplicity. Prior studies indicate that about 40% of people
modify their first regimen.
Marina Klein of McGill University in Montreal and colleagues evaluated
why people switch first-line regimens for reasons other than inadequate viral
suppression – for example, to reduce side-effects or improve convenience –
and the link between switching and subsequent virologic failure. Suppressed
viral load was defined as two HIV RNA measurements below 50 copies/ml at least
one month apart; virological failure was defined as viral load above 1000
This analysis looked at 2807 people living with HIV in the multi-site Canadian CANOC cohort who started combination ART between
2005 and 2012. Most (87%) were men and the median age was 42 years. The median
baseline CD4 cell count was 260 cells/mm3, 12% had a history of
injecting drugs and 15% had hepatitis C virus (HCV) co-infection.
Overall, a total of 1003 participants (36%) switched from their
first-line ART regimen. Among these, 391 people (14%) switched once while 612 (22%)
switched two or more times. The median time from treatment initiation to the
first switch was approximately 10 months and the median CD4 count when
switching was 450 cells/mm3, showing substantial immune recovery
since starting treatment. Participants were more likely to switch away from non-nucleoside reverse transcriptase inhibitor (NNRTI)-based
Looking at characteristics associated with switching, women
were more likely than men to change their regimen. Women made up 11% of people
who never switched, 14% of those who switched once and 18% of those who
switched multiple times. Older people, people who injected drugs and people with HIV and HCV
co-infection were also somewhat more likely to switch two or more times, as
were those with lower CD4 counts.
However, in a multivariate analysis controlling for other
factors, the only significant predictors of switching were sex, with men being
about half as likely to switch multiple times (adjusted odds ratio [OR] 0.53);
age, with older people less likely to switch once (adjusted OR 0.88); and
province of residence, with those in Ontario and Quebec being more likely to
make a first switch.
In addition, people who started ART after 2008 – when more
tolerable drugs were available – were about 30% less likely to switch multiple
times (adjusted OR 0.69), and those who had been on their first regimen longer
were more likely to subsequently switch (adjusted OR 1.45 for one switch, 1.72
for multiple switches).
Another statistical analysis found that switching regimens
was associated with a 35% increased risk of virological failure overall
(adjusted OR 1.35). However, when looking at specific characteristics, the difference
was significant only for men, who had a 65% lower risk of virological failure (adjusted
OR 0.35), and people who inject drugs, who were nearly three times more likely to
experience treatment failure (adjusted OR 2.85).
"Even with modern ART, regimen switch while
virologically suppressed was common," with changes presumably due to
tolerability, simplification or to avoid drug interactions, Klein and her
colleagues summarised. "Switching from first ART regimen while
virologically suppressed was associated with subsequent virologic
Switching ART due to tolerability concerns "might
represent specific patient characteristics where ART intolerance is a marker
for factors associated with poor adherence" they suggested. They added
that the greater likelihood of women switching regimens and experiencing
subsequent virological failure might reflect changes in treatment related to
However, they noted that this analysis did not actually
identify specific reasons for switching or assess the role of adherence. Development
of drug resistance has not yet been assessed.
switching while virologically suppressed may not be completely benign,"
the researchers concluded. "Closer follow up among patients switching for
non-virologic reasons may be warranted as such switches may serve as a marker
for problems with adherence or poorer tolerance of medications."