Rationale and design of a randomized factorial clinical trial of pharmacogenetic and adherence optimization strategies to promote tobacco cessation among persons with HIV.

Abstract Background Tobacco use is approximately three times more common in people living with HIV (PLWH) than the general population. Moreover, current behavioral and pharmacological smoking cessation interventions are less effective for PLWH, highlighting a need for novel ways to optimize tobacco cessation treatments in this group. Prior research indicates that personalized treatment based on the nicotine metabolite ratio (NMR), a biomarker of nicotine metabolism, and augmenting smoking cessation medication adherence may improve cessation treatment for PLWH. Methods In this 2 × 2 factorial design trial, 488 smokers with HIV receive 12 weeks of smoking cessation medication along with randomization to 1) tailor the smoking cessation drug to their metabolism or not, and 2) provide additional counseling on smoking cessation medication adherence or not. Those randomized to the pharmacogenetic optimization arm receive varenicline or the nicotine patch based on their NMR (varenicline for fast metabolizers and the nicotine patch for slow metabolizers) and those in the control arm receive varenicline. Those randomized to the experimental adherence counseling arm receive Managed Problem Solving (MAPS) targeting their smoking cessation medication and those in the control arm receive standard counseling. Conclusion PLWH on suppressive antiretroviral therapy who smoke lose more life-years due to tobacco use than to their HIV infection, and have lower response rates to current evidence-based treatments for smoking cessation. Both the NMR tailoring and MAPS interventions have the potential to optimize treatments for tobacco use among this population. If effective, this trial may demonstrate ways to further improve long-term health outcomes for PLWH.