Optimizing Treatment of Co-occurring Smoking and Unhealthy Alcohol use among PWH in Nairobi, Kenya

Project Summary. Sub-Saharan Africa is home to >70% of people with HIV (PWH) globally. It is also burdened with rising rates of tobacco use, high rates of unhealthy alcohol use, and high rates of tobacco and alcohol co-use. These disparities are amplified in PWH in this region. Tobacco users drink more and alcohol users smoke more and quit less than mono-users. Tobacco combines with alcohol to exert a destructive synergy expressed, in particular, in extremely high rates of aerodigestive (especially esophageal) cancers. Kenya is the 7th most populous country in Africa, with 54 million people, 1.6 million of whom are PWH. Tobacco and alcohol use rates in Kenya, including Kenyan PWH, are higher than those in most sub-Saharan nations. Incidence rates of esophageal cancer in Kenya are 2.9 times those of the US in men and 8.4 times those of the US in women. There is an enormous need for better strategies to manage tobacco and alcohol co-use in Kenya and throughout the world. Our group has been engaged in tobacco treatment research for PWH in Nairobi, Kenya since 2018. We are completing a 2 x 2 factorial design randomized controlled trial (RCT) of Positively Smoke Free intensive behavioral counseling ± bupropion, and we have collected detailed information on alcohol usage in Kenyan PWH in the course of that study. We have created and piloted a new version of Positively Smoke Free counseling to include content related to alcohol co-use and strategies to cut down or quit alcohol use. Cytisine is a nicotinic acetylcholine receptor partial agonist that has been used for tobacco treatment since the 1960’s, mostly in Eastern Europe, Russia, and Canada. Multiple trials of cytisine, conducted almost exclusively in White participants, have demonstrated that its efficacy in promoting smoking cessation is comparable to varenicline, the first line tobacco treatment in the US. Cytisine is inexpensive, safe, and does not interact with antiretroviral therapies. It is a potent treatment for alcohol dependence in animal models, but data to support its use for this purpose in humans are scarce. There is virtually no published experience with cytisine on the African continent, but Kenya’s Ministry of Health has expressed interest in this affordable agent if it is proven effective in a Kenyan population. A placebo controlled trial of intensive counseling ± cytisine for Kenyan PWH who smoke and drink alcohol heavily will advance the science of tobacco and alcohol co-use, it will strengthen the case for cytisine use in Kenya and other low- and middle-income nations if effective, and it will address significant health disparities in a resource-constrained area of the world. In this application to renew 1R01CA225419, we propose a 2 x 2 factorial RCT comparing Positively Smoke Free including alcohol-referent content to standard care and comparing cytisine to placebo. We will study both tobacco and alcohol use endpoints as primary and secondary outcomes. We will also examine putative mediators of intervention effects on study outcomes. Finally, we will complete detailed cost analyses to estimate the cost-effectiveness of the trial interventions in relation to the trial’s tobacco and alcohol use outcomes.