CCSG Pilot: Adjunctive Theta Burst Stimulation (TBS) or Attentional Bias Modulation and Smoking Cessation in People Living with HIV/AIDS (PLWHA): A Randomized Clinical Trial

People living with HIV/AIDS (PLWHA) smoke at nearly three times the rate of the general population. These extraordinary smoking rates are associated with greater AIDS-related cancer, non-AIDS related morbidity including non-AIDS-defining cancer, cardiovascular disease, pulmonary disease, and mortality. Smoking significantly impacts the progression and outcome of HIV disease and has been identified as the leading contributor to premature mortality in PLWHA. Suboptimal results with current smoking cessation strategies makes identifying new adjunct strategies an area of need. Our pilot study proposal aims to modulate craving and attentional bias towards smoking cues in people living with HIV/AIDS (PLWHA) using transcranial magnetic stimulation (TMS), with functional MRI (fMRI) brain correlates. TMS is a form of noninvasive brain stimulation and modulates neural activity using tiny doses of focused electricity. The TMS paradigm we would be performing is called theta burst stimulation (TBS), which is potent, short, and efficient. It has shown to cause neuroplasticity even with a single session and was approved by the FDA for treatment of major depressive disorder in 2019. Targeting the left dorsolateral prefrontal cortex (DLPFC) will modulate craving and attentional bias that is closely associated with craving. For this pilot study, 40 subjects will perform the attentional bias task, craving scale and neuroimaging before and after the TBS/ sham TMS session, to compare changes in these paradigms between these interventions. Attentional bias would be measured with eye tracking, craving will be assessed with tobacco craving questionnaire (TCQ-SF). We will aim to recruit 20 subjects in each arm of our trial (total of 40) from the BlueGrass HIV Clinic, who have an established pipeline for enrolling PLWHA patients in clinical trials. Although there is limited data on TMS in smoking, there have been no TMS studies done in PLWHA. If funded, the investigative team would work closely to conduct the study, analyze the data and submit it for publication. Dr Himelhoch is an expert in smoking cessation and HIV. Dr Rush is an expert in attentional bias and addiction clinical trials. Drs Rakesh, Wesley and Adams will bring their expertise in neuromodulation and neuroimaging to the team. Dr Burris will help the team with subject recruitment strategies. The Patient Oriented and Population Science SRF headed by Dr Burris will perform phone screens for clients from the Bluegrass HIV Clinic who wish to participate in the study. Dr Shelton who heads the Biostatistics SRF is also part of the team. Of note, an R01 grant application comprising these aims was submitted to National Institute on Drug Abuse (NIDA) in October 2020 (R01 DA053852). It was reviewed favorably, although the reviewers thought the inclusion of pilot data would strengthen the application. Hence, the findings of this pilot study would be aimed at expediting resubmission of this grant application with a plausible optimistic outcome. This pilot study and R01 grant application will aim to advance TBS as an adjunct treatment strategy for smoking cessation in PLWHA.