In the United States, women with a lower socioeconomic status and women from racial or ethnic minority backgrounds continue to bear a disproportionate HIV burden [1]. According to the Centers for Disease Control and Prevention (CDC), women made up 18% of the new HIV diagnoses in 2022, with 83% of those cases representing transmission through heterosexual contact and 16% representing transmission through injection drug use. The HIV diagnosis rates for Black and Hispanic women are 10 and 3 times, respectively, the rates for White women [1]. Women with substance use disorders (SUDs) are particularly vulnerable to HIV transmission due to the greater likelihood of engaging in vaginal or anal sex without using a condom, concurrent sexual relationships, sex in exchange for drugs, money, or other items, and sexual coercion from experiencing sexual abuse or assault by intimate partners [2-6]. Inequities experienced by women, including relationship power and control differentials and physical or sexual violence, further influence women’s engagement in both the risk behaviors that increase their likelihood of contracting HIV as well as the potential preventive measures. To adequately address the syndemic effect of substance use, HIV, and trauma [7], interventions must be specifically developed for the unique needs of this population.

Pre-exposure prophylaxis (PrEP) is a medication with demonstrated efficacy in reducing HIV transmission, including among heterosexual women [8]. PrEP removes the barrier of partner consent, thus empowering women to engage in their own HIV prevention strategies. This is an important factor among women who have difficulty negotiating safer sex practices with their partners due to relationship power imbalances [9-11]. Despite the effectiveness of PrEP, uptake has been slow among women, and the reasons for this, particularly among women with SUDs, are not completely understood [12].

According to the CDC, in 2019, approximately 1.2 million adults had PrEP indications. Yet, there are disparities among those with PrEP indications, with males more likely to have been prescribed PrEP than females [13]. HIV prevention research has overwhelmingly focused on men who have sex with men, with few studies designed specifically to study PrEP uptake in women [14,15]. Evidence suggests that low perceived risk and concerns about side effects (most commonly nausea and vomiting) are barriers to PrEP use [16]. Some women perceive themselves to be at low risk for HIV despite engaging in condomless sex and sex while using substances [17-19]. In contrast, studies examining PrEP knowledge and attitudes have found low rates of initial knowledge with high levels of interest among women once they are informed of the benefits of PrEP for HIV prevention [14,15]. This interest, however, does not always result in PrEP uptake.

Social and structural factors such as poverty, race or ethnicity, inequities, discrimination, and lack of empowerment combine as barriers to HIV prevention for women with SUDs [9-11,20-25]. Extending availability and access to effective HIV prevention strategies, such as PrEP, may help overcome these intersecting barriers and is consistent with the nation’s “Ending the HIV Epidemic” plan by “preventing new HIV transmissions by using effective interventions which include PrEP” [26]. In addition to the individual barriers to PrEP use mentioned above, there are also social and structural barriers to PrEP uptake. These include, but are not limited to, perceived stigma, lack of access to knowledgeable providers, and mistrust of health care providers and health care systems [12,14,15,27]. Lack of access to PrEP services and provider reluctance to prescribe PrEP are also significant barriers, given that women have reported a preference for conversations about HIV prevention to be initiated by medical providers [17]. Expanding PrEP uptake to women is a vital component of the nation’s plan [28]. However, research on PrEP initiation among women is limited [29].

A few studies have found daily oral PrEP to be effective for reducing HIV acquisition in heterosexual women [8,30]. However, 2 major trials specifically examining PrEP in women were unable to demonstrate the efficacy of oral PrEP because of low adherence [31,32]. The few published research studies on PrEP uptake among women have taken place in a variety of US and international settings where available resources and barriers to uptake and adherence may vary considerably, thus making it difficult to ascertain the potential for PrEP to reduce HIV acquisition among heterosexual women. The notable absence of published findings on effective interventions to increase PrEP uptake and adherence among women represents a significant gap in the research literature [33]. A recent review of best practices for increasing PrEP uptake and persistence in the United States identified 9 interventions meeting the criteria for best practice, with only 1 of the 9 including women as participants [34]. The 1 study included in the review, which included women, reported only 6 of the 198 participants identified as women [35]. One promising intervention using motivational interviewing with women was not included as meeting best practice guidelines due to low participant enrollment [36]. Additional research on interventions designed to increase PrEP uptake and adherence among women is needed [15]. A meta-analysis of oral PrEP use among women found only a 61% reduction in HIV acquisition risk among women who reported 75% adherence to a daily PrEP regimen [37]. Researchers have called for greater attention to both PrEP uptake and adherence among women and future studies that focus on developing and evaluating methods to enhance adherence and greater reliance on laboratory-based versus self-reported adherence measures [38].

Integrating HIV prevention into environments where individuals are already engaged in other services helps to increase access to care. In a previous study, researchers found that offering HIV testing and prevention counseling within SUD treatment programs resulted in increased rates of receiving these preventive services [39]. This is an example of work at an individual level to increase HIV testing behavior and at a structural level to remove barriers to care by increasing the SUD treatment program’s capacity to provide HIV prevention services [40]. It has been recommended that SUD treatment programs routinely offer HIV testing to all participants and linkage to primary medical care for individuals who test positive for HIV as a means of increasing access to HIV care [41]. However, despite the well-known associations among substance use, HIV, and sexual risk, it is estimated that only about half of SUD treatment programs offer HIV prevention services [42,43].

The addiction treatment clinic setting is ideally situated to provide additional services for HIV prevention. In recognition of the important role that addiction providers can play in the adoption and delivery of PrEP services and to identify potential barriers to implementing PrEP, researchers have explored providers’ perspectives on including PrEP as part of addiction treatment [44]. To our knowledge, PrEP and HIV prevention services have not been optimally integrated into the addiction treatment clinic environment; thus, the study team proposed to develop an addiction clinic–based behavioral intervention designed to increase PrEP uptake for racial or ethnic minority women.

This project is guided by the Information-Motivation-Behavioral Skills (IMB) [45] model, shown in Figure 1. The IMB model of health behavior change posits that information, motivation, and behavioral skills are key determinants of engaging in health behaviors. This model has been applied to various health promotion behaviors, including HIV treatment and prevention [40-43]. Specific to HIV prevention, the 3 fundamental determinants of HIV risk reduction include information regarding how HIV is transmitted and methods for preventing HIV infection; motivation to change risky behaviors; and training in behavioral skills necessary for engaging in specific preventive acts [46]. In HIV research, the IMB model has been used to inform interventions for medication adherence in persons living with HIV [47] and has some preliminary evidence for utility with PrEP uptake and adherence interventions [48-50]. The IMB model has also been used to guide the development of interventions to increase PrEP uptake and adherence using mobile health (ie, text messaging, appointment reminders, and medication reminders using mobile devices) [51,52]. Previous research supports the use of mobile technologies as a cost-effective and convenient method for increasing health-promoting behaviors [53].

Research supports the IMB model in the development of interventions aimed at increasing willingness to use PrEP in people who use drugs with high HIV risk [54]. Guided by the IMB model, our addiction clinic–based PrEP uptake and adherence intervention provides knowledge of PrEP effectiveness and side effects and offers motivational incentives for increasing PrEP uptake using an innovative remote-delivery monetary incentive application (Scene mobile app; formerly Emocha [55,56]) that provides the behavioral skills necessary to effectively use PrEP (eg, adherence and side effect management) including video directly observed therapy to monitor medication taking. Video directly observed therapy allows participants to upload videos of themselves taking their medication through a video-enabled device such as a smartphone so that their treatment teams can verify that medication has been taken. In addition, the Scene Health mobile app includes videos showing behavioral skills, a library of motivational messages, and frequently asked questions to address barriers to PrEP use.

Within the context of the IMB model, the research team anticipates that the addiction clinic–based behavioral intervention will improve PrEP uptake and adherence among racial or ethnic minority women engaged in SUD treatment. By co-locating services within the addiction clinic, the intervention will address moderating factors (access to care and adherence support) that have been barriers to successful PrEP uptake and adherence.

This study aims to develop an addiction clinic–based behavioral intervention for increasing PrEP uptake and adherence among racial or ethnic minority women who engage in sexual and substance use behaviors associated with HIV transmission. To accomplish this, investigative team proposes a 3-phase study, as illustrated in Figure 2, to address 3 specific aims: (1) to elicit information on knowledge and attitudes about PrEP use and obtain feedback about the design of an addiction clinic–based behavioral intervention for racial or ethnic minority women with sexual and substance use behaviors associated with HIV transmission; (2) to develop an addiction clinic–based behavioral intervention to promote PrEP uptake and adherence in women undergoing treatment for SUD who are susceptible to HIV infection; and (3) to assess initial efficacy, feasibility, and acceptability of the addiction clinic–based behavioral intervention.

The primary study setting will be the outpatient treatment research clinic of the Center for Neurobehavioral Research on Addiction (CNRA), a university-supported center of excellence within the Louis A Faillace, MD Department of Psychiatry and Behavioral Sciences at UTHealth Houston. Allies in Hope (formerly AIDS Foundation Houston), established in 1982, is a community-based organization providing HIV prevention, HIV treatment, counseling, and case management to Houston residents. Allies in Hope will be the referral site for the control group (ie, standard-of-care treatment condition) in the phase 3 pilot randomized controlled trial.

Participants are eligible to participate in all phases of the study if they are self-identified as Black/African American and Hispanic/Latina women, aged 18 years or older, diagnosed with an SUD per DSM-5 (Diagnostic and Statistical Manual of Mental Disorders [Fifth Edition]) criteria [57], HIV-negative, sexually active (ie, vaginal or anal sex) with a male within the past 6 months, not using PrEP for HIV prevention at the time of screening, fluent in English, and own or have regular access to a smartphone.

Participation in the current study is limited to English-speaking individuals because intervention materials have not yet been translated into Spanish. Future research will use instruments translated into Spanish and include interview and data collection materials in Spanish to address the unique needs of individuals whose primary or preferred language is Spanish.

Based on information obtained in phase 1 and the IMB model, the study team developed an addiction clinic–based behavioral intervention, Theater Testing of the Cultivating HeAlth Resilience Growth & Empowerment (Take CHARGE), that provides PrEP-related information, motivational messaging, and behavioral skills necessary to use PrEP effectively. The intervention will include a PrEP service component to be delivered in the addiction treatment clinic by a nurse practitioner, leveraging the existing SUD treatment and HIV prevention infrastructure and removing accessibility barriers. This intervention will be provided alongside standard SUD treatment which consists of participation in individually delivered, evidenced-based intervention (eg, cognitive behavioral therapy) focused on quitting or reducing substance use delivered by a master’s-level counselor, psychologist, or psychology intern under the supervision of a licensed psychologist.

The intervention will consist of 4 weekly sessions that can be delivered through a HIPAA (Health Insurance Portability and Accountability Act)-compliant videoconferencing platform. Sessions will be approximately 30 minutes in length and are intended to increase knowledge of PrEP, increase positive attitudes toward PrEP, and decrease behaviors that place individuals at risk for HIV infection with a goal of increasing PrEP uptake and PrEP adherence.

The study team used the IMB domains to develop the addiction clinic–based behavioral intervention. Specifics on how each domain informed the development of the intervention are outlined below.

The investigative team will rigorously pilot test the degree to which the addiction clinic–based behavioral intervention promotes increased PrEP adherence compared with standard linkage to PrEP. The investigative team will randomly assign 60 women to 1 of the 2 conditions. Participants in both the intervention and control groups will continue to receive evidence-based behavioral therapy for SUDs (ie, cognitive behavioral therapy with licensed counselors).

The investigators will recruit 60 BlackBlack or Hispanic women to participate in the study. The investigators will invite individuals who are engaged in or initially enrolling in treatment for SUDs at the CNRA. The research assistant will describe the study by informing participants that this is an HIV prevention study focusing on women engaged in treatment for SUD and will not directly impact their regular SUD treatment. Potential participants will be screened over the phone by the research assistant and informed of the purpose of the study. Those meeting inclusion criteria and agreeing to participate will sign an informed consent form and receive a copy. After completing the informed consent process, participants will be randomized to the intervention or control group.

The study team will recruit eligible participants by posting flyers, through word of mouth (through addiction treatment staff referral), and advertising in local print sources (newspapers and magazines). Recruitment and enrollment began in May 2024 and will continue through March 2025.

Participants in both arms will complete baseline surveys and follow-up surveys administered at 4 weeks, 10 weeks, and 16 weeks post baseline. Data sources to examine efficacy will include a computer-assisted self-interview (self-report measures), pharmacy records, Scene Health app data, and medical records.

Master’s-prepared clinicians (eg, mental health counselors and psychologists) will conduct a comprehensive diagnostic interview using the Mini International Neuropsychiatric Interview (MINI) [60] and the National Institute on Drug Abuse Modified Assist [61]. This will be used to determine a diagnosis and severity of SUD and any co-occurring mental health disorders. Other data collection will include baseline assessment of outcome variables and potential moderators. These self-report questionnaires will be delivered through a REDCap survey. The link will be emailed or texted to the participant based on their preference. Refer to Table 1 for a description of measures and outcomes of interest.

The primary outcome of interest is PrEP uptake defined as filling the PrEP prescription and taking at least 1 dose of the medication by 2 weeks following their visit with the PrEP provider. The primary outcome will be measured at 12 weeks post completion of the 4-week motivational sessions.

The secondary outcome of interest is daily PrEP adherence as measured by the proportion of videos uploaded showing medication being taken (intervention group only), the proportion of self-reported daily adherence (intervention and control group), levels of tenofovir (TFV) urine concentrations (>1000 ng/mL) [75] detected in urine measured at 12-weeks post-PrEP initiation (both groups). According to previous research, urine concentrations of TFV at >1000 ng/mL is indicative of use of oral PrEP in the previous 3 days (high adherence), detectable levels of TFV but <1000 ng/mL are indicative of low adherence and undetectable levels of TFV suggesting nonadherence [75]. Studies have also shown that directly observed therapy is useful for interpreting PrEP adherence. This provides an additional layer of certainty regarding this method of measuring this important secondary outcome [76]. Medication adherence for long-acting injectable PrEP will be determined by examining medical records for the timing of the dose.

Other outcomes of interest include intervention feasibility (enrollment rate, session attendance, use of Scene Health, and study retention), and intervention acceptability (client satisfaction scores).

A data safety monitoring board affiliated with the CNRA will provide oversight for this study including the possibility of loss of confidentiality. The Scene Health mobile app is HIPAA-compliant and allows for secure messaging and encrypted videos, Access to the app requires a participant to log in with credentials. Videos submitted to the app are not available in the device gallery and videos are deleted from the device once received by Scene Health’s secure server. Only approved project staff will have access to the participant data via the “Backstage” by Scene Health web portal.

Generalized linear modeling will model effects of the proportion of participants who fill their prescription and take at least one dose as a function of intervention group. In unique models, generalized linear modeling will evaluate 2 secondary outcomes as a function of intervention group: (1) dichotomous verification of adherence based on urine TFV levels >1000 ng/mL (no vs yes), and (2) TFV levels >1000 ng/mL indicating recent adherence, detectable levels of TFV but <1000 ng/mL indicating low adherence and undetectable levels of TFV suggesting nonadherence [75].

Where necessary, generalized linear mixed modeling will account for correlated observations by including random effects (eg, random intercepts or slopes for participant ID in longitudinal analyses of adherence over time). Survival analysis (ie, Kaplan-Meier estimation; Cox proportional hazards regression) will evaluate PrEP retention. Additional analyses will evaluate descriptive statistics about the enrollment rate, study retention, session attendance, and participant satisfaction. Analyses will be performed in R (R Foundation for Statistical Computing) [77]. Statistical significance will be measured at an α of <.05 for all a priori hypothesis tests. Hypothesis 3a: (primary outcome) compared with standard treatment, the intervention will result in a greater proportion of participants who fill their first PrEP prescription. Hypothesis 3b: compared to standard treatment, the intervention will result in greater adherence to PrEP in those who filled their prescriptions (self-report and laboratory verified urine tenofovir concentrations). Hypothesis 3c: the intervention will be feasible and acceptable by women as demonstrated by enrollment rate, study retention, session attendance, and participant satisfaction scores.

This study is approved by the University of Texas Health Science Center at Houston Committee on the Protection of Human Subjects (HSC-MS-21-0451). This study is registered on ClinicalTrials.gov (NCT06158607).

The investigators anticipate that the addiction clinic–based behavioral intervention will address the structural and social barriers often cited for their associations with a lack of PrEP uptake and adherence among racial or ethnic minority women. This intervention is innovative in its integration of PrEP services co-located with SUD treatment setting and using mobile health technology to support adherence to PrEP. Although the focus of the intervention is primarily on individual level factors (knowledge, motivation, and skills), there are some aspects of the intervention that help address interpersonal and structural level barriers. The availability of PrEP services within a familiar treatment setting removes a barrier of access for women with substance use disorder. The intervention’s added focus on communication and strategies for seeking social support and knowing when and when not to disclose about PrEP use addresses interpersonal barriers. Through this intervention, the goal is that women will be empowered to engage in their own HIV prevention strategies, promote PrEP as a low-barrier and safe tool for HIV prevention, and remove potential concerns (eg, side effects, confidence in PrEP adherence, stigma from providers, family, and friends) [78,79], to reduce HIV-related disparities in Black and Hispanic women.

The current study is primarily limited by scale, given that this is a pilot study of HIV-negative Black and Hispanic women living in Houston, Texas, United States, findings may not be generalizable to areas with divergent demographic characteristics. In addition, participants in the control group will provide self-reported data, which may be subject to recall bias. Due to the limited nature of this pilot study mechanism, it is not possible to follow participants for a longer term as would be necessary to draw conclusions about medication adherence. This will be accomplished through a future larger-scale trial of the intervention. In addition, to test the feasibility and acceptability of the Scene Health app components, we required that participants have regular access to a smartphone. The study team’s experience with this population indicates that the vast majority of participants have access to smartphones. However, this can change on an individual bases as participants have difficulties with paying bills, lose phones, etc. The study team will monitor participants’ access as 1 of the aspects of feasibility for this type of intervention to be further explored in a future implementation study. Finally, participants must speak English to meet eligibility requirements, thus potentially limiting the generalizability of findings for Hispanic women who may only speak Spanish.

Despite these limitations, this study has several strengths. First, there are limited studies specifically focused on developing effective behavioral interventions for women with SUD. Second, tailoring the intervention with the use of videos and content representative of women of color has the potential to engage this population more effectively in care than existing interventions. Third, the intervention uses an app that can help support PrEP adherence by providing information, motivation, and behavioral skills necessary to increase the likelihood of starting and staying on PrEP.

The addiction clinic–based behavioral intervention aims to increase PrEP uptake and adherence among racial or ethnic minority women who engage in sexual, and substance use behaviors associated with HIV transmission. This addiction clinic–based behavioral intervention has the potential to reduce HIV-related disparities among Black and Hispanic women with SUDs. Findings from this study can also serve as a framework for future culturally appropriate HIV prevention interventions for women.