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

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.

Rate and correlates of tobacco treatment during a primary care visit for a largely urban and African American sample of smokers.

Introduction: Evidence-based treatments for tobacco use are under-utilized and primary care visits may be an opportune time to address this gap. This study examined the rate at which primary care visits included tobacco use treatment and examined patient demographics, smoking characteristics, attitudes about tobacco use treatments, and comorbidities as correlates of treatment provision. Methods: This prospective study assessed demographics, smoking characteristics, attitudes about tobacco use treatments, and comorbidities via interview prior to a primary care visit among 105 patients. One week following the appointment, 85 patients were reassessed for the tobacco use treatments they received during their appointment (i.e., asked about their tobacco use, advised to quit, and provided with a referral to a tobacco use treatment program or an FDA-approved tobacco use medication). Results: 93% of patients were asked about their tobacco use, 74% were advised to quit, 37% were provided with a referral for tobacco use treatment, and 27% received an FDA-approved medication (16% NRT, 11% varenicline or bupropion). Patients with higher quit motivation and who endorsed that medications can reduce cravings were more likely to report receiving tobacco use medication. Patients with a self-reported substance abuse history were less likely to report receiving tobacco use medications. Conclusions: The provision of tobacco use medications within primary care remains low. Strategies to increase patient quit motivation and help patients understand that tobacco use medications can mitigate cravings may increase use. Strategies may also be needed to ensure that patients with comorbid substance abuse still receive tobacco use treatments.

Fluorescent monitoring of RNA assembly and processing using the split-spinach aptamer.

As insights into RNA's many diverse cellular roles continue to be gained, interest and applications in RNA self-assembly and dynamics remain at the forefront of structural biology. The bifurcation of functional molecules into nonfunctional fragments provides a useful strategy for controlling and monitoring cellular RNA processes and functionalities. Herein we present the bifurcation of the preexisting Spinach aptamer and demonstrate its utility as a novel split aptamer system for monitoring RNA self-assembly as well as the processing of pre-short interfering substrates. We show for the first time that the Spinach aptamer can be divided into two nonfunctional halves that, once assembled, restore the original fluorescent signal characteristic of the unabridged aptamer. In this regard, the split-Spinach aptamer is represented as a potential tool for monitoring the self-assembly of artificial and/or natural RNAs.