BackgroundNicotine replacement therapy (NRT) and short messaging service (SMS)-based tobacco cessation interventions have demonstrated effectiveness in reducing tobacco use in many populations, but evidence is needed on which tailored treatments are most efficacious in meeting the complex medical and psychosocial factors confronting people living with HIV (PLWH) in sub-Saharan Africa (SSA). This paper describes the protocol of a study to test the efficacy of both NRT and a tailored SMS-based tobacco use cessation intervention among PLWH in Uganda and Zambia.MethodsIn a randomized controlled trial, 800 adult PLWH who use tobacco will be recruited by health care professionals at HIV treatment centers where they are receiving care. Participants will be randomized to one of the four study arms: (1) standard of care [SOC; brief clinician advice to quit combined with HIV education and information aimed at encouraging HIV treatment adherence (with no mention of tobacco) delivered via text messages]; (2) SOC + 12 weeks of NRT; (3) SOC + 6 weeks of SMS text messages to support quitting tobacco use (SMS); or (4) SOC + NRT + SMS. Participants will receive a cell phone and solar panel with power bank for charging the phone. The main outcome is cessation of tobacco use by study participants verified by urinary cotinine (< 15 ng/mL) at 6 months post-enrollment. As a secondary tobacco use outcome, we will measure 7-day point-prevalence abstinence (7 consecutive days of no tobacco use) measured by self-report and biochemically-verified at 4 weeks, 8 weeks, and 3 months post enrollment.DiscussionOur study will provide insight into the efficacy, feasibility and applicability of delivering tobacco cessation interventions through health care professionals combined with tailored tobacco cessation SMS text messaging in two countries with different tobacco use patterns, policy environments, and health care resources and provide needed information to providers and policymakers looking for cost-effective tobacco cessation interventions. The previously tested SMS-platform to be used in our study is uniquely positioned to be scaled in low- and middle-income countries worldwide, in which case evidence of even modest success in reducing the prevalence of tobacco consumption among PLWH could confer enormous health and economic benefits.Trial registration: ClinicalTrials.gov Identifier NCT05487807. Registered August 4, 2022, https://clinicaltrials.gov/ct2/show/record/NCT05487807