Sub-Saharan Africa has the highest number of people living with HIV (PWH) in the world with over 70% of all cases. In this region, many people also use tobacco and drink alcohol, often at high rates. Tobacco and alcohol use are even more common in PWH and often occur together. People who smoke are more likely to drink heavily, and people who drink heavily are more likely to smoke and less likely to quit either habit. When tobacco and alcohol are used together, they significantly increase the risk of certain cancers, especially cancers of the throat and esophagus.

Kenya, home to 54 million people, has 1.4 million PWH. Tobacco and alcohol use in Kenya are higher than in most other countries in sub-Saharan Africa, including among PWH. Rates of esophageal cancer in Kenya are shockingly high—nearly three times higher in men and over eight times higher in women compared to rates in the United States. This shows an urgent need for better ways to help people in Kenya manage and quit using tobacco and alcohol.

Cytisine, a medication developed in the 1960s, has been used for decades in countries like Russia, Canada, and parts of Europe to help people quit smoking. It’s safe, affordable, and works well, with effectiveness similar to a leading U.S. treatment called varenicline. Unlike varenicline, cytisine does not interact with HIV medications, making it a promising option for PWH. Animal studies also suggest it may help treat alcohol dependence, though more human studies are needed. However, cytisine has hardly been used or studied in Africa, including in Kenya, where the government is interested in exploring its potential benefits.

This study will test whether combining intensive counseling with cytisine can help Kenyan PWH who both smoke and drink heavily. It will use a structured design to compare two interventions: one using specialized counseling programs (focused on tobacco and alcohol) versus standard care, and another using cytisine versus a placebo. The study will measure both smoking and drinking outcomes, as well as explore how and why the interventions work. It will also assess the cost-effectiveness of these approaches.

The results will provide valuable information for policymakers, healthcare providers, and community leaders in Kenya and beyond. If cytisine proves effective, it could become a powerful tool to reduce smoking, heavy drinking, and related health problems, especially in resource-limited settings. 

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, particularly in extremely high rates of aerodigestive (especially esophageal) cancers. Kenya is the 7th most populous country in Africa, with 54 million people, 1.4 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 a need for better strategies to manage tobacco and alcohol co-use in Kenya and throughout the world.

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.

This study evaluating 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. The study will employ a 2 x 2 factorial design 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. Results of this study will provide policymakers, community leaders and clinicians with critical evidence of the most effective smoking and unhealthy alcohol use treatments for PWH.