Grant Details
Grant Number: |
3R01CA243914-05S1 Interpret this number |
Primary Investigator: |
Schnoll, Robert |
Organization: |
University Of Pennsylvania |
Project Title: |
Testing Novel Pharmacogenetic and Adherence Optimization Treatments to Improve the Effectiveness of Smoking Cessation Treatments for Smokers with HIV |
Fiscal Year: |
2023 |
Abstract
The advent of anti-retroviral therapy (ART) for people living with HIV/AIDS (PLWHA) substantially improved life
expectancy but, now, PLWHA who smoke lose more life-years due to tobacco use than they do to their HIV
infection. Unfortunately, the rate of smoking among PLWHA in the US is about 40%. The limited tobacco use
treatment research with PLWHA indicates that behavioral treatments and medications (nicotine patch and
varenicline) yield moderate effects on cessation, with quit rates that are considerably lower than they are for the
general population. Thus, there is a critical need to identify novel ways to optimize tobacco cessation treatment
for smokers with HIV. Two factors are highly predictive of cessation outcomes with pharmacotherapy, in the
general population and among PLWHA. First, a smoker's rate of nicotine metabolism, characterized by the
nicotine metabolite ratio (NMR, a marker of CYP2A6 gene variants), predicts cessation both for varenicline and
nicotine patch. Our studies with general population and HIV-infected smokers show that personalizing the choice
of medications for smokers using the NMR can increase efficacy and reduce toxicities, an approach highlighted
by the NCI. Second, adherence to smoking cessation medications, in the general population and among
PLWHA, rarely exceeds 60% and non-adherence lowers cessation rates 2-3 fold. We developed the
Managed Problem Solving (MAPS) intervention which is endorsed by the CDC as an evidence-based
intervention for medication adherence among PLWHA. Thus, the application's premise is that incorporating
intervention components to tailor tobacco use medications (varenicline or patch) with the NMR and increase
adherence to the medication using MAPS will optimize tobacco treatments for PLWHA. To test this premise, we
will conduct a rigorous multi-site randomized clinical trial with 488 HIV+ smokers to evaluate NMR-
tailored treatment and MAPS as optimization strategies for tobacco dependence treatment for PLWHA. We
will use a factorial design to examine: 1) The effects of the NMR-tailored and/or MAPS interventions on end-of-
treatment (EOT) and 6-month smoking cessation rates (primary aim); 2) Mediators of the NMR-tailored and
MAPS interventions (secondary aim); and 3) Moderators of the NMR-tailored and MAPS
interventions (exploratory aim). Our overall approach is consistent with the Multiphase Optimization Strategy
which has gained prominence for guiding the evaluation of interventions for enhancing tobacco use
treatment effectiveness. Addressing these aims will determine: the use of adherence and pharmacogenetic
optimization of smoking cessation treatment for PLWHA, the mechanisms that underlie the effects of these
optimization strategies on cessation outcomes, and the variation in the effects of these optimization
strategies across sub-groups of PLWHA. In the end, this trial will help understand if getting the right
medication to the right person and helping to make sure they sufficiently use that medication optimizes
tobacco cessation treatment for this population.
Publications
None. See parent grant details.