Stimulant use disorder continues to rise as a devastating public health issue in the United States, accounting for more than 57,000 deaths in 2022—a near 5-fold increase since 2015 [1] Among people living with HIV, stimulant use is particularly prevalent (>5% to 15% in the general population of people with and 30% in safety-net patient populations living with HIV) and represents a key challenge for maintaining overall health [2-4]. Both methamphetamine and cocaine have been repeatedly associated with antiretroviral therapy (ART) nonadherence, HIV viremia, and progression to AIDS; by some estimates, people living with HIV using stimulants demonstrate double the odds of ART nonadherence compared to those not using stimulants [5-9].

Contingency management (CM) is the first-line treatment for stimulant (methamphetamine and cocaine) use disorder and has also been used to promote ART adherence for people living with HIV [10-15]. This behavioral treatment—in which patients receive tangible incentives for demonstrating abstinence (eg, measured by drug-negative urine)—is highly efficacious, supported by a multitude of randomized controlled trials [10,16,17]. In addition, research suggests that CM can also be efficacious for ART adherence, although these studies were limited by the potential inaccuracy of indirect adherence measurements (eg, electronic pill bottle cap monitoring does not equate to ingested medication) [11-15].

Despite its demonstrated efficacy, the uptake of CM remains limited in both safety-net and ambulatory settings. While these settings represent the main source of medical care for many high-need patients, feasibility concerns have largely impeded CM implementation. Frequently described barriers include insufficient training and awareness, logistic concerns related to program execution, cost and resource intensiveness of programs requiring multiple weekly visits, and staff reluctance to provide financial incentives [18-21]. In addition, addressing syndemic behaviors simultaneously (by incentivizing both stimulant use reduction and ART adherence through a single “multitarget” intervention) is an important opportunity to seize. To effectively reach people living with HIV who are most in need of this treatment, there is an urgent need for feasible CM models that target stimulant use and ART adherence in ambulatory safety-net settings.

Leveraging harm reduction principles will be essential for addressing the needs of safety-net populations with comorbid HIV and stimulant use disorder. Abstinence from stimulants can be an unrealistic, unwanted, or a less proximate goal for people with severe stimulant use disorder, who may be using daily or chronically [22]. Efforts to emphasize stimulant use reduction rather than abstinence have shown promise in promoting overall health; for example, in a secondary analysis of 13 randomized controlled trials, reduced use of methamphetamine and cocaine was associated with global improvement of psychosocial functioning and severity of drug-related problems, as well as improved depression and fewer drug-seeking behaviors [23]. Although CM is traditionally structured to promote abstinence, new models that incentivize stimulant use reduction and other positive health behaviors may be more aligned with patient goals and needs in the safety-net setting.

To optimize care for safety-net populations living with comorbid stimulant use disorder and HIV, we designed a novel CM program incentivizing both stimulant use reduction and ART adherence in the HIV ambulatory setting, called CoMBo (Contingency Management for Both HIV and Stimulant Use Disorder). CoMBo involves point-of-care (POC) tests that detect stimulant use within a 3- to 4-day window and offer once-weekly visits in contrast to traditional CM programs that test urine 2 to 3 times per week to confirm abstinence. In addition, we use a novel POC, a urine-based tenofovir assay that allows for real-time assessment of adherence to tenofovir-based ART [24,25]. This technology enables simultaneous assessment of tenofovir adherence and stimulant use by using one urine sample, facilitating a truly paired intervention.

In this paper, we present a full description of an implementation effectiveness pilot delivering CM with paired incentives in the HIV ambulatory setting and describe a protocol for the quantitative and qualitative evaluation of program feasibility and acceptability (the CoMBo study). We hypothesize that (1) this program will be acceptable to staff and participants and (2) offering once-weekly CM (as opposed to multiple-times per week) to achieve stimulant reduction (as opposed to abstinence) in low-barrier medical homes of people living with HIV will be feasible.

The following are the objectives of this study:

We will conduct a pilot, single-arm, hybrid implementation effectiveness trial of dual-incentive CM targeting stimulant use reduction and improved ART adherence in 2 low-barrier, ambulatory HIV clinics. We use the Behavior Change Wheel framework to tailor this intervention to meet the needs of our target safety-net population (Table 1). This study design will allow for the investigation of implementation feasibility in our target setting, while also gathering data on the intervention’s impact on target behaviors. The study will occur over a period of 9 months; patient recruitment will occur during the first 6 months of the study on a rolling basis. Following this pilot, we will solicit feedback on intervention acceptability using in-depth qualitative interviews with participants and clinic staff. The study has been registered as a clinical trial (ClinicalTrials.gov NCT06564792).

This study will be conducted at 2 subclinics at San Francisco General Hospital’s Ward 86, one of the oldest HIV clinics in the country serving more than 2600 people living with HIV in the county safety net. Ward 86 provides wraparound care with co-located behavioral health, social work, case management, laboratory, and pharmacy services. The Women’s Clinic is an interdisciplinary, team-based model of care providing HIV, substance use disorder, drop-in services, and mental health care to people identifying as cis- or transwomen living with HIV at Ward 86, serving 234 patients as of July 2022. The POP-UP clinic is another interdisciplinary, team-based clinical program within Ward 86 providing low-barrier, drop-in primary care to patients with HIV experiencing homelessness. At least 30% of the Ward 86 population report regular stimulant use, with approximately 40% of Women’s Clinic patients and 90% of POP-UP patients reporting stimulant use. By co-locating CM into low-barrier medical homes for vulnerable people living with HIV, we aim to decrease barriers to CM engagement for patients with comorbid stimulant use disorder and HIV.

Recruitment, enrollment, and study procedures will occur at Ward 86, with targeted recruitment from the aforementioned clinics. We aim to recruit participants living with HIV who (1) are on tenofovir-based ART regimens, (2) are diagnosed with severe stimulant use disorder (according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria, measured with the Structured Clinical Interview for DSM-5, using at least near daily), (3) have suboptimal ART adherence (defined as at least one instance of HIV viral load over 200 copies/mL in the preceding 18 months or reporting periods of discontinuation within last 18 months), (4) are interested in reducing frequency of stimulant use and improving ART adherence, and (5) speak either English or Spanish [26]. On the basis of the estimated prevalence of comorbid stimulant use disorder and HIV within our target safety net, we aim to recruit approximately 40 participants.

Primary care providers within the safety net may refer participants via email or direct messaging through the electronic health record system (Epic), and participants may also spontaneously walk-in for enrollment without a referral. Eligibility criteria are assessed via phone (for referrals) or in-person (for walk-ins) and confirmed via the electronic health record (last detectable viral load, confirmation of stimulant use disorder diagnosis, and ART regimen) before enrollment. Participants who meet the eligibility criteria are offered an enrollment visit, in which they provide informed consent and complete baseline assessments.

One CM provider will be trained to lead all CM activities with supervision by the principal investigator, an addiction medicine specialist. Training includes (1) POC device training; (2) completing the free, virtual “Contingency Management Overview Training” offered by the Recovery Incentives Program at the University of California, Los Angeles; (3) addiction medicine–specific intensive MI through a 2-day training workshop [34].

At enrollment, participants will receive a visual schema describing the incentive structure and indicating where or when they may come in for CM visits (Multimedia Appendix 1).

The materials required for conducting study visits include fishbowl with paper slip incentives (Figure 1), stimulant POC tests, tenofovir POC tests (Figure 2), gift cards, and sign-out sheets (to confirm receipt of gift cards and record barcodes, as required by our funding mechanism), and timeline follow-back form (Multimedia Appendix 1).

The number of incentives earned during each visit will be automatically calculated via REDCap (Research Electronic Data Capture; Vanderbilt University; calculated field using special functions) after input of POC results.

All data will be captured and stored using REDCap electronic data capture tools hosted at University of California, San Francisco [35,36]. Most data metrics (described in Table 2) will be extracted from patient interviews during baseline and study visits, although viral loads will be extracted from patient’s electronic medical record.

Baseline assessments (Table 2) will extract patient variables relating to sociodemographics, substance use history, and HIV history, including HIV viral load before participation. We will also collect POC results at baseline (although no incentives will be earned from these results), perform 7-day timeline follow-back to assess baseline frequency of stimulant use, and record visit-related characteristics (length of visit and amount in US $ received through a priming draw; Multimedia Appendix 1) [37].

Visit assessments will assess recent stimulant use and ART adherence, capture POC results, and record visit characteristics (including number of incentives earned). At each visit, we will objectively assess each target behavior through POC testing (used to calculate incentives), subjectively assess stimulant use using 7-day timeline follow-back, and subjectively assess ART adherence using a 3-point Likert scale question (Table 2).

Upon intervention conclusion after 12 study visits, we will record the viral load most proximate to the patient’s last attended visit.

Participants will be asked to engage in the qualitative evaluation following study completion (week 12 from enrollment), during either the end of their final study visit or when they return to the home clinic for routine care. Any participant who enrolled and completed at least one study visit will be eligible to enroll. Eligible staff will be identified by the study coordinator, who will recommend staff who meaningfully contributed feedback regarding the pilot rollout or who interfaced with the pilot’s day-to-day functioning. For example, we anticipate the clinic’s head nurses and primary social workers to meet this criteria.

Interviews will occur at each home clinic during clinic hours. They will be conducted by 1 to 2 trained researchers with extensive experience conducting qualitative interviews and background in HIV or addiction medicine. Participants will be consented by the interviewer before the interview. In-depth interview guides have been developed using the CFIR framework in order to systematically evaluate setting, intervention, individual, and process characteristics influencing program acceptability (Table 4; Multimedia Appendices 2 and 3). All interviews will be recorded; the interviewer will refrain from using identifying language during the record process, for example, by using participants’ study ID numbers instead of their name. Interviews are estimated to last approximately 45 minutes. Each interviewee will receive US $50 worth of gift cards for their participation.

We will create a purposive sample of 14 trial participants, with priority recruitment of at least 7 participants who completed fewer than 50% of CM visits and 7 participants who completed more than 50% of CM visits (Table 4). This sample size will largely depend on the number of participants recruited, but we aim to interview approximately 30% of our total target sample size (ie, 14 participants in a pool of 40). Interviews will seek to (1) understand participant experiences in the primary care–based, stimulant, and adherence-targeted CM intervention and (2) explore how multilevel factors might positively and negatively influence engagement with multitarget CM (eg, role of relationships in the clinic, and concurrent synergistic clinical goals such as gender-affirming surgery, intervention factors such as drop-in visits, and reinforcement schedule, etc). We are secondarily interested in identifying how participant goals for stimulant use reduction are related to HIV management, if at all, and how drivers of stimulant use and additional determinants of health (eg, homelessness, intimate relationships, etc) interact with HIV and stimulant use disorder management.

We will also conduct qualitative interviews with 5 to 10 care providers and staff who were involved in participants’ care or who interfaced with the intervention’s activities (eg, referred participants and assisted with program logistics). This final sample size will depend on how many care providers meaningfully interact with this pilot; we have identified a minimum of 5 care providers whose roles interface with the intervention, and we expect this number to increase as we integrate the problem into the everyday functioning of our target clinics. We seek to investigate perceived appropriateness of dual-incentive CM in the low-barrier HIV care context, elucidating perspectives on (1) the intervention’s compatibility with existing clinic processes, (2) how well the intervention met clinic needs and relative importance of these needs, and (3) changes to promote long-term sustainability.

This study was approved by the Institutional Review Board at University of California, San Francisco (23-38747). Written informed consent will be obtained from participants before enrollment, consenting to study activities, review of electronic medical records by research staff, and secondary analyses using study data. Consents will be available in English and Spanish (Multimedia Appendices 4 and 5). Participants may opt out of the study at any point.

To maintain participant privacy, any data relating to the study will be stored in either REDCap or an encrypted Box folder hosted by the University of California, San Francisco. Only members of the research team will have access to any participant data stored in REDCap. Study data will not be recorded or linked to the patients’ electronic medical records. Audit of gift cards will be performed by the San Francisco Department of Public Health, per the Controller’s Office protocol. No participants currently incarcerated will be enrolled in this study.

Compensation will be provided for participation in the qualitative evaluation and will consist of a US $50 gift card that can be used at most grocery stores.