The use of varenicline (Chantix) appears to be relatively safe in people living with HIV, and when combined with counseling, could significantly increase the number of smokers who are able to quit cigarettes, according to a French study presented at CROI 2015 in Seattle, Washington.
"The combination of varenicline with counseling led to [more than] double the likelihood of quitting smoking," said Patrick Mercié, M.D., who presented findings from the placebo-controlled study, ANRS 144 Inter-ACTIV.
Despite the more-than-double likelihood, the proportion of people who were able to give up smoking cigarettes for a whole year remained low -- only about 18% -- illustrating the need for further research into additional interventions.
Over the last two decades, the use of antiretroviral therapy has increased the life expectancy of people living with HIV to almost that of the general population, and rather than the opportunistic infections that were seen in the past, comorbidities such as non-AIDS malignancies and cardiovascular disease have become important challenges in the current management of HIV.
Some of this increased risk appears to be directly due to HIV infection or the immune response -- but recent studies have shown that smoking (which is common among people living with HIV in industrialized settings) also contributes significantly to the increased risk of comorbidities in the HIV-positive population.
For instance, one recent study reported that smoking almost triples the risk of heart attack in people living with HIV, while another study presented at CROI found that smoking contributed more to the burden of non-AIDS related cancers in HIV-positive individuals than any other modifiable risk factor. Therefore, promoting smoking cessation among people living with HIV is critically important.
Varenicline acts as a partial antagonist of alpha-4 beta-2 nicotinic acetylcholine receptors, reducing nicotine craving. It is approved to help smokers in the general population, but it has also been associated with a higher rate of cardiovascular disease and psychiatric side effects. In fact, the U.S. Food and Drug Administration (FDA) recently updated the drug's label to include warnings that varenicline could alter the way people respond to alcohol (reducing tolerance/increasing drunkenness) and has been associated with a rare risk of seizures, and changes in mood or behavior.
Aware of some of these issues, the French researchers concluded that there was a need to demonstrate that varenicline was effective and safe (paying specific attention to the incidence of psychiatric and cardiovascular disease events) in people living with HIV.
The study was performed at 30 ANRS (French Research Agency) clinical centers in France. Adults living with HIV were eligible to enroll if they had smoked at least 10 cigarettes per day over the past year, were motivated to stop smoking, had no current codependency to psychoactive substances and no current diagnosis of depression or known history of suicidal attempts.
Participants were randomly assigned to either varenicline or placebo plus counseling with a 12-week treatment period. During the first week, the dose was titrated from 0.5 mg once daily (for three days) up to 0.5 mg twice a day, and then to 1 mg twice daily at the end of the first week. Counseling had been specifically developed by a specialist in tobacco addiction and included 10 or 15 visits over one year scheduled with the active contribution of the participants. After the end of the treatment period, participants were followed for a further 36 weeks.
Self-reported tobacco abstinence was confirmed by exhaled carbon monoxide measurements at nine weeks and at intervals up to 48 weeks.
The primary endpoint was smoking cessation over the long term -- using the stringent definition of continuous abstinence from smoking from week 9 through week 48 without the use of any smoking cessation treatments other than the trial's treatment. The secondary endpoints included continuous abstinence rate from week 9 to 12 and adverse events.
Overall, of the 248 eligible participants enrolled between October 2009 and December 2012, however, some did not start the study drug, so the modified analysis included 102 individuals on varenicline and 111 on placebo.
There were no differences in the baseline characteristics. The mean age of participants was 45 years; 24% had had an AIDS diagnosis, and 95% had an undetectable viral load at study entry. On average, participants were heavy smokers for a long duration. A large proportion of them had already attempted to quit in the past; and their Fagerstrom scores (a measure of nicotine dependence) showed a high dependency to nicotine. Assessments for mental health and motivation suggested the population was moderately affected by depression but participants were highly motivated to quit smoking.
The percentage of participants continuously abstinent from week 9 to week 48 was higher in the varenicline group: 18% versus 7%.
Looking at abstinence prevalence per visit, the largest effect was observed at week 12 (34% versus 13%), but the rates of continuous abstinence fell gradually over time.
Throughout the study, the median CD4+ cell counts remained stable in both groups, as did the proportion of participants with an undetectable viral load.
In the second phase of the study, those who failed to quit smoking were offered open-label varenicline. These data were not included in the efficacy analysis but were included in the safety data regardless of initial randomization.
There was one death in the study but this was the result of an assault and not a drug-related incident. As expected, side effects of grade 3/4 were most frequent in those on varenicline -- most of these were psychiatric, including sleep disorders, night sweats, depression and behavioral disorders. Mercié acknowledged, however, that one limitation of the study was that it excluded the individuals with concomitant substance abuse issues.
There were a few gastrointestinal side effects including nausea and overeating. However, there was no significant difference in the occurrence of cardiovascular disease and no cerebrovascular events were reported.
"The use of varenicline in addition to counseling was safe, well tolerated and successful in nearly one-fifth of the participants," Mercié said, but added that how to best support the remaining individuals to quit smoking remains a challenge.
"Further research is still required in terms of acceptability, safety and adherence for existing or new treatments," Mercié concluded.
Theo Smart is an HIV activist and medical writer with more than 20 years of experience.
Follow Theo on Twitter: @theosmart.