Despite significant advances in HIV prevention and treatment, HIV and AIDS remain a leading cause of morbidity and mortality in sub-Saharan Africa (SSA) [1]. In 2021, Zambia’s adult HIV prevalence (10.8%) was the seventh highest globally [1], with more than 15,000 new infections among youth aged 15 to 24 years [2]. Young people with HIV experience substantial disparities across the HIV care continuum, including lower antiretroviral therapy (ART) adherence, missed clinic visits, and lower viral suppression than older individuals [3,4]. Interventions designed for youth are crucial to improve adherence and viral suppression and to reduce mortality.

Young people with HIV are in emerging adulthood, a developmental stage marked by increasing independence, identity exploration, and risk-taking behaviors that may compromise HIV self-management [5]. Young people with HIV often exhibit poor HIV management, including suboptimal medication [6] and appointment adherence, limited engagement in health care [7], risky sexual behavior, alcohol use [8], and other substance use [9]. Zambian youth have the highest rate of regular alcohol use among 73 low- and middle-income countries [10] and the highest prevalence of cannabis use in Africa (37.2%) [11]. Alcohol use has synergistic and additive effects on HIV comorbidities [12] and accelerates HIV disease [13]. It is linked to increased HIV transmission [14], poor ART adherence [15], and worse outcomes across the treatment cascade [16]. In Zambia, commonly used substances include marijuana, cigarettes, opiates, cocaine, and inhalants [17], and 47% of youth have used a psychoactive substance [18].

Stigma is a well-documented barrier to health-seeking behaviors [19], engagement with the health care system [20], and adherence to treatment [21] across health conditions, including HIV [22]. For young people with HIV, stigma contributes to risky sexual behavior and substance use [23], reduces social support [24], and exacerbates mental health concerns such as depression [25]. Young people with HIV in Zambia widely experience HIV-related stigma across socioecological levels. Together, stigma and mental health are important targets for HIV interventions.

Strikingly, few interventions address self-management of both HIV and substance use in young people with HIV [26]. Healthy Choices (HC) is one of the few interventions that has demonstrated improvements in viral load and alcohol trajectories in young people with HIV [27,28]. HC also showed improvement in depression [29], marijuana use [28], and HIV-related stigma [30]. HC is a 4-session program that integrates motivational interviewing (MI) tailored for young people with HIV [27,31]. However, in-person HC can be limited by time, clinic engagement, and implementation barriers. Delivering HC via mobile health (mHealth) may increase access and engagement, reduce cost and time for youth and staff, and support implementation in clinics.

mHealth has been rapidly expanding across African countries, with widespread success in delivering health services [32]. Mobile connections in Zambia were equivalent to 91.4% of the total population in early 2022 [33]. SMS text messaging is inexpensive, nonintrusive, and widely integrated into the daily lives of youth in SSA [34]. Motivational text messaging (MTM) interventions have improved ART adherence and viral suppression among young people with HIV in SSA [35]. MTM offers a low-cost, sustainable, and youth-friendly way to extend the reach of HC sessions.

This study will adapt HC for mobile delivery and integrate MTM to improve HIV self-management and reduce substance use among young people with HIV in Zambia. It will develop and pilot a scalable, youth-friendly intervention to improve ART adherence, engagement in care, and health outcomes.

We propose to develop and pilot a multicomponent mHealth intervention to improve HIV self-management and reduce substance use among young people with HIV in Zambia. First, we will adapt the 4-session HC intervention for mobile delivery and develop MTM to enhance the impact of mobile HC (mHC). Both components will be delivered using the Computerized Intervention Authoring System (CIAS). Second, we will conduct a pilot trial using the multiphase optimization strategy (MOST) framework to evaluate the feasibility, acceptability, and preliminary efficacy of intervention components and identify the most promising intervention component or combination of components. This study will lay the groundwork for a future fully powered efficacy trial and may provide a scalable model for improving outcomes among young people with HIV in Zambia.

The information-motivation-behavioral skills (IMB) model and the socioecological model (SEM) will serve as the conceptual frameworks. Both theoretical models have been applied to HIV health behaviors [36] and ART adherence [37]. Although the IMB model focuses on individual-level determinants of behavior, the SEM captures the broader individual-, social-, and structural-level factors that influence HIV self-management and substance use. The proposed intervention focuses primarily on behavior change at the individual level while also addressing social- and structural-level influences, such as stigma, depression, and barriers to care engagement. According to the IMB model, behavior change results from the joint function of accurate information about risk behaviors (eg, risks of nonadherence to ART and substance use), motivation to change behavior, and behavioral skills to perform the behavior (Figure 1). According to the SEM, health behaviors are influenced by the complex interplay of multilevel factors related to these elements. We will develop intervention content to address both individual and multilevel influences to facilitate HIV self-management and reduction of substance use among young people with HIV in Zambia.

Young people with HIV will be recruited from 2 large HIV clinics in Lusaka Province to ensure sample diversity. Lusaka is home to 3.4 million people (18.8% of Zambia’s population) [39] and has high HIV rates and high phone ownership among youth [40]. The Kanyama First Level Hospital (KFLH) serves a population of approximately 120,000 individuals aged 10 to 29 years in a high-density, low-income township near Lusaka [41]. The Matero Urban Health Centre (MUHC) is located in urban Lusaka and serves a population of 247,451 [41]. We will recruit young people with HIV from a broad range of socioeconomic backgrounds. MUHC typically serves middle- to higher-income families, whereas KFLH primarily serves lower-income communities. Together, these clinics provide access to diverse youth populations with substantial HIV burden and co-occurring substance use.

There are 3 phases in the study: phase 1 (formative research), phase 2 (intervention adaptation), and phase 3 (pilot randomized controlled trial [RCT]).

Young people with HIV will be included if they provide informed consent. Inclusion criteria will be as follows: (1) living with HIV and aged between 18 years 0 months and 24 years 11 months; (2) visual analog scale showing <80% medication adherence in the last month and unhealthy alcohol use or any drug use in the last month [50]; and (3) able to understand, read, and speak English, Nyanja, or Bemba. Exclusion criteria are as follows: (1) a serious cognitive or psychiatric problem that would compromise ability to provide informed consent and (2) current enrollment in another HIV intervention study. Smartphone ownership is not required; a smartphone with internet access will be provided at no cost to participants who do not have one.

This pilot MOST design–based trial is designed to estimate main effects of mHC and MTM and their interaction using a 2×2 factorial study design. Using G*Power 3.1.9 (ANOVA procedure), with effect size f=0.35, α=.05, and sample size=100 (25 per condition), statistical power is 80% for detecting main effects of mHC and MTM and 73% for detecting their interaction. Our proposed pilot trial is not an efficacy study, but our sample is large enough to detect a medium to large effect size of mHC and MTM.

Youth presenting at either clinic will be screened by the clinic staff for eligibility and, if applicable, referred to research staff for informed consent. After providing verbal consent, the research staff will determine eligibility. Screening, enrollment, and baseline assessment will occur on the same day whenever possible; otherwise, they will be completed within 1 week. After written consent, participants will be asked to provide a phone number or email and contact information for a family member and/or friend in case they cannot be reached.

Table 2 summarizes the study measures, including primary and secondary or exploratory outcomes. Self-report measures will be administered using cloud-based computer-assisted self-interviewing at baseline and 3- and 6-month follow-up. Blood samples for dried blood spot (DBS) testing for HIV viral load will be collected at baseline and 3 and 6 months. Sexually transmitted infection outcomes, including syphilis, gonorrhea, and chlamydia, will be assessed at baseline and 6 months. In computer-assisted self-interviewing, participants view each question and response options on a private iPad (Apple Inc) screen and enter responses directly into password-protected Qualtrics (Qualtrics).

The primary acceptability outcome will be measured by the System Usability Scale, a 10-item Likert scale assessing usability. A score of >70 indicates that technology-based interventions are acceptable [51]. We will also assess interest in future use of the intervention at study completion. For feasibility, we will assess responses to MTM, number of mHC sessions completed, cumulative time spent in mHC, and recruitment rates. Preliminary efficacy outcomes include ART adherence and alcohol use. ART adherence will be measured using (1) the Young Adult Adherence Interview with a visual analog scale [52], (2) 4-week percent of doses taken, and (3) DBS biological testing. Results of DBS testing will be triangulated with self-reports. We will assess integrated behavior model constructs, including knowledge, attitudes, motivations, and behavioral skills related to taking ART, and important contextual factors (depression and HIV stigma).

We will estimate retention rates overall and per condition and examine differences across conditions using chi-square tests. We will assess differences in acceptability using 2-tailed t tests or Mann-Whitney U tests. Minimum criteria for acceptability and feasibility will include a mean System Usability Scale score ≥70 and at least 50% of participants responding to MTM at least once and completing at least 2 mHC sessions [51].

To test the main effects and interactions between components using data from the 2×2 factorial study design, we will use ANOVA with effect coding (−1=“no” condition; +1=“yes” condition) rather than dummy coding. The preliminary intervention effects on ART adherence and substance use outcomes will be assessed using linear mixed-effects models, while viral suppression will be analyzed using mixed-effects logistic regression models. Models will adjust for baseline values of the outcome and relevant covariates and will account for repeated assessments over time. Missing data will be handled using full information maximum likelihood estimation. Effect sizes will be estimated for the primary outcomes.

We will make a preliminary selection of components that have achieved main effects. This selection will then be re-evaluated considering any substantial interaction effects to understand how the components work in combination. Depending on the optimization criterion (viral suppression), this will be combined with other information (eg, cost, feasibility, and scalability) to make a final selection of components. This information will inform the development of an optimized intervention package.

This protocol was reviewed and approved by the institutional review boards of the University of Massachusetts Chan Medical School in the United States (STUDY00001496) and the University of Zambia (4548-2023).

We anticipate developing a multicomponent mHealth intervention to improve ART adherence and HIV self-management and to reduce substance use among young people with HIV in Zambia. young people with HIV in Zambia often have difficulty taking medication as prescribed, miss medical appointments, and report unhealthy alcohol and other drug use, which may compromise viral suppression and long-term health outcomes. Combining mHC and MTM may help improve adherence, strengthen self-management skills, and reduce substance use among Zambian young people with HIV.

We will evaluate the feasibility, acceptability, and preliminary efficacy of an mHealth intervention combining mHC and MTM. On the basis of our theoretical models of behavior change, we anticipate that the intervention will be beneficial, although this remains to be determined. If successful, this intervention can improve the health of those affected by HIV or AIDS and reduce future rates of HIV infection in Zambia. Our research is integrated within Zambia’s national HIV prevention effort. The commitment and ongoing involvement of the University of Zambia will allow this research to serve as a model for HIV prevention among high-risk groups, especially in SSA and other low-resource settings.

The project will be conducted to develop an optimized technology-based intervention for young people with HIV in Zambia and prepare for a future large-scale RCT. For a fully powered R01 project, we propose a multisite study testing the efficacy of mHC and MTM using a type 2 effectiveness-implementation design, with testing of intervention effectiveness in improving ART adherence, viral suppression, and substance use outcomes, while gathering information on implementation, including cost analysis to assess the relative cost of implementing the intervention.

This study addresses a critical problem—suboptimal ART adherence, substance use, and challenges with HIV self-management—among young people with HIV in Zambia. We are developing 2 potentially synergistic, technology-based, theory-driven intervention components aimed at improving HIV self-management and substance use outcomes. Despite major advances in HIV treatment, many young people with HIV continue to face barriers to sustained adherence and viral suppression. Our study addresses these barriers through a youth-centered mHealth approach. It is responsive to the need for scalable interventions to improve HIV outcomes. If successful, this study will pave the way for the scale-up of mHealth interventions to improve HIV care outcomes among young people with HIV in Zambia and other low-resource settings. The NIH peer review summary statement is provided in Multimedia Appendix 2.