The smoking cessation drug varenicline (Champix,
or Chantix in the United States) helped more people with
HIV to stop smoking than counselling alone, but less than 20% were able to remain
abstinent for a year, according to the results of a French study presented at
the Conference on Retroviruses and Opportunistic Infections (CROI 2015) last
week in Seattle, USA. The smoking cessation rates in this study were comparable
to those previously seen for HIV-negative people using varenicline or other methods – across the board only a
minority manage to quit long-term.
Studies have shown that a large proportion of people with HIV smoke
tobacco – higher than comparable HIV-negative groups of the same sex and age.
In Europe, it is estimated that at least half of people living with HIV are
smokers. It is well known that smoking contributes to a host of health problems
ranging from cardiovascular disease to cancer. Since people with HIV appear to
be at greater risk for some of these conditions already, smoking cessation
takes on added importance.
Patrick Mercie
from Hôpital Saint-André in Bordeaux presented
findings from ANRS 144 Inter-ACTIV, a study comparing smoking cessation rates
after a year for people treated with varenicline or placebo. The study,
sponsored by the French national HIV and hepatitis research agency, was
conducted at 30 ANRS clinical centres between October 2009 and January
2014.
Pfizer's varenicline
is a partial nicotinic receptor agonist that helps reduces craving for nicotine
and dampens the pleasurable feelings associated with smoking. It was approved
in the US and European Union in 2006.
This phase 3 study enrolled 248 smokers living
with HIV who were motivated to quit; 213 started therapy and were included in the final
analysis. They smoked at least 10 cigarettes per day (median 20 per/day), had
been smokers for around 25 years on average and more than 80% had previously
tried to quit at least once.
More than 80% of participants were men with a median age of 45 years. Almost
all were on antiretroviral therapy, most had an undetectable viral load and the
median CD4 cell count was high at over 600 cells/mm3. At study entry,
they were not experiencing depression and were not dependent on other drugs.
Participants were randomly assigned to receive varenicline (starting at 0.5mg
once daily and escalating to 1mg twice daily) or placebo for a 12-week
treatment period, along with smoking cessation counselling. They were then
followed up for an additional 36 weeks to determine continuous smoking
cessation rates. Self-reported abstinence was confirmed using exhaled carbon
monoxide measurements at week 9 and periodically through to the end of
follow-up.
Participants using varenicline were significantly more likely to abstain
from smoking than those in the placebo arm. By the end of treatment at 12 weeks,
34.3% of varenicline recipients were not smoking compared to 12.6% of placebo
recipients. By 48 weeks, however, cessation rates had fallen to 17.6% and 7.2%, respectively, in a modified
intent-to-treat analysis. The likelihood of continuous abstinence at 48 weeks was
nearly three times higher in the varenicline arm
compared to the placebo arm (odds ratio 2.8).
Varenicline was generally safe and well-tolerated, though there were
concerns about some specific side-effects. Previously, suicidal thoughts or
attempts, other psychiatric symptoms and cardiovascular abnormalities have been
reported among HIV-negative people taking varenicline. In fact, US prescribing
information for Champix includes a
'black box' warning about neuropsychiatric symptoms such as hostility,
depression and suicide. However, systematic reviews and large observational
studies have not shown that these adverse events occur more often with
varenicline compared to placebo.
In this study the most common adverse events were nausea, abdominal pain
and sleep disorders. Participants in the varenicline arm reported more drug-related
adverse events overall (51 vs 26%), more grade 3/4 or moderate-to-severe adverse
events (25 vs 13%) and more psychiatric adverse events (42 vs 28%). The psychiatric
events included sleep disorders, insomnia, nightmares, depression and
hallucinations. There were nine reported grade 3/4 drug-related psychiatric
adverse events in the varenicline arm and none in the placebo arm. However,
depression occurred with similar frequency in the varenicline and placebo arms
(4 vs 6%, respectively). No serious drug-related cardiovascular events were
reported in either arm of the study. HIV viral load levels and CD4 counts
remained stable in both arms.
In this first
large-scale randomised trial of varenicline in people living with HIV, varenicline was "safe and well
tolerated" and "as effective as [an] adjunct to counselling as in the
general population," the researchers concluded, with adverse events
"as expected in the [HIV-]uninfected population."
"Varenicline
with appropriate counselling appears to offer some benefit and should be
considered in the HIV case management," they recommended.
Prior studies of HIV-negative people have shown that varenicline is more
effective than the smoking cessation medication bupropion (Zyban, Wellbutrin),
nicotine replacement products such as patches or counselling alone. In one
randomised clinical trial, rates of sustained abstinence at one year were
23% with varenicline, 15% with bupropion and 10% with placebo. No intervention,
however, has been shown to work for more than about one-quarter to one-third of
people who use it. Recent research indicates that combining interventions – for
example varenicline plus a nicotine patch – is likely to be more effective than
any single method used alone.
At a CROI press conference about HIV-related
comorbidities, Mercie said that while varenicline is generally safe for people
with HIV, "it remains non-indicated for patients with uncontrolled
psychiatric conditions."
In this study, 18% of participants were taking
efavirenz (Sustiva or Stocrin, also in Atripla), too few to analyse separately. Some of the reported
psychiatric events associated with varenicline are similar to side-effects of
efavirenz, and there may be reason for concern about using these two
medications together.
"Our study shows that varenicline is effective in helping people
living with HIV to quit smoking," Mercie stated
in an ANRS press release. "To achieve these results, however, certain
conditions have to be met: the patient must be motivated, well-advised and
followed up regularly by a smoking cessation specialist, must not be in an
anxious or depressed state, and must have well-controlled HIV infection."