Optimizing adherence in HIV prevention product trials: Development and psychometric evaluation of simple tools for screening and adherence counseling.

BACKGROUND: Low adherence in recent HIV prevention clinical trials highlights the need to better understand, measure, and support product use within clinical trials. Conventional self-reported adherence instruments within HIV prevention trials, often relying on single-item questions, have proven ineffective. While objective adherence measures are desirable, none currently exist that apply to both active and placebo arms. Scales are composed of multiple items in the form of questions or statements that, when combined, measure a more complex construct that may not be directly observable. When psychometrically validated, such measures may better assess the multiple factors contributing to adherence/non-adherence. This study aimed to develop and psychometrically evaluate tools to screen and monitor trial participants' adherence to HIV prevention products within the context of clinical trial research. METHODS AND FINDINGS: Based on an extensive literature review and conceptual framework, we identified and refined 86 items assessing potential predictors of adherence and 48 items assessing adherence experience. A structured survey, including adherence items and other variables, was administered to former ASPIRE and Ring Study participants and similar non-trial participants (n = 709). We conducted exploratory factor analyses (EFA) to identify a reduced set of constructs and items that could be used at screening to predict potential adherence, and at follow-up to monitor and intervene on adherence. We examined associations with other variables to assess content and construct validity. The EFA of screener items resulted in a 6-factor solution with acceptable to very good internal reliability (α: .62-.84). Similar to our conceptual framework, factors represent trial-related commitment (Distrust of Research and Commitment to Research); alignment with trial requirements (Visit Adherence and Trial Incompatibility); Belief in Trial Benefits and Partner Disclosure. The EFA on monitoring items resulted in 4 Product-specific factors that represent Vaginal Ring Doubts, Vaginal Ring Benefits, Ring Removal, and Side Effects with good to very good internal reliability (α = .71-.82). Evidence of content and construct validity was found; relationship to social desirability bias was examined. CONCLUSIONS: These scales are easy and inexpensive to administer, available in several languages, and are applicable regardless of randomization. Once validated prospectively, they could (1) screen for propensity to adhere, (2) target adherence support/counselling, and (3) complement biomarker measures in determining true efficacy of the experimental product.

Using High-Risk Adolescents' Voices to Develop a Comprehensible Cognitive Behavioral Therapy-Based Text-Message Program.

At-risk adolescents' comprehension of, and preferences for, the content of a text-message (SMS) delivered, cognitive behavioral therapy (CBT)-based depression prevention intervention was investigated using two qualitative studies. Adolescents with depressive symptoms and a history of peer violence were recruited from an urban emergency department. Forty-one participants completed semi-structured qualitative interviews. Thematic analysis using deductive and inductive codes were used to capture a priori and emerging themes. Five major themes were identified: CBT-based messages resonated with at-risk adolescents; high levels of peer violence, comorbid symptoms, and prior exposure to the mental health system were variables affecting preferred content; participants endorsed emotional regulation messages, but found mindfulness content difficult to understand via SMS; cognitive awareness and restructuring content was most acceptable when framed by self-efficacy content; adolescent participants generated applicable CBT content in their own voices. Overall, CBT-informed content was able to be distilled into 160-character text messages without losing its comprehensibility.

A Comparative Pre-Phase I Study of the Impact of Gel Vehicle Volume on Distal Colon Distribution, User Experience, and Acceptability.

For persons at risk of HIV infection who practice receptive anal intercourse (RAI), topical rectal microbicides represent a promising option for coitally dependent protection. The study compared colorectal distribution and user sensory experiences of two different volumes of rectal gel for suitability as rectal microbicide. Eight HIV-negative men with a history of recent RAI were enrolled into a two-period, sequence-randomized dosing study comparing 3.5 and 10 ml of radiolabeled (1 mCi 99mTc-DTPA) universal placebo, hydroxyethyl cellulose gel. Each participant received two doses in the research unit, one of each volume, separated by a washout period of at least 2 weeks. Each research unit dose was followed by a self-administered take-home dose in the context of preparing for RAI. Safety and gastrointestinal distribution were assessed after the research unit doses, safety, perceptibility, and acceptability, were assessed after take-home doses. There were no adverse effects of Grade 2 or higher and all resolved spontaneously. Both volumes were well tolerated and received high acceptability scores. Perceptibility scores showed meaningful effect size differences ranging from Cohen's d = 0.5 to d = 1.2. The 3.5 and 10 ml gel volumes distributed similarly (p > .2) within the rectosigmoid, ranging from 0.69 to 18.84 cm and 1.21 to 19.01 cm from the anorectal junction, respectively. Both volumes covered the typical gastrointestinal distribution of ejaculate following simulated intercourse based on other studies. Either of these gel volumes could reasonably be pursued for the next phase of development of rectal microbicides.

"That's Where the Arguments Come in": A Qualitative Analysis of Booster Sessions Following a Brief Intervention for Drug Use and Intimate Partner Violence in the Emergency Department.

Although booster phone calls have been used to enhance the impact of brief interventions in the emergency department, there has been less number of studies describing the content of these boosters. We conducted a qualitative analysis of booster calls occurring two weeks after an initial Web-based intervention for drug use and intimate partner violence (IPV) among women presenting for emergency care, with the objective of identifying the following: progress toward goals set during the initial emergency department visit, barriers to positive change, and additional resources and services needed in order to inform improvements in future booster sessions. The initial thematic framework was developed by summarizing codes by major themes and subthemes; the study team collaboratively decided on a final thematic framework. Eighteen participants completed the booster call. Most of them described a therapeutic purpose for their drug use. Altering the social milieu was the primary means of drug use change; this seemed to increase isolation of women already in abusive relationships. Women described IPV as interwoven with drug use. Participants identified challenges in attending substance use treatment service and domestic violence agencies. Women with substance use disorders and in abusive relationships face specific barriers to reducing drug use and to seeking help after a brief intervention.

A Depression Prevention Intervention for Adolescents in the Emergency Department.

PURPOSE: To evaluate acceptability and feasibility of a theoretically based two-part (brief in-person + 8-week automated text message) depression prevention program, "intervention for DepressiOn and Violence prevention in the Emergency department" (iDOVE), for high-risk adolescents. METHODS: English-speaking emergency department (ED) patients (age 13-17, any chief complaint) were sequentially approached for consent on a convenience sample of shifts and screened for inclusion based on current depressive symptoms and past-year violence. After consent, baseline assessments were obtained; all participants were enrolled in the two-part intervention (brief in-ED + 8-week two-way text messaging). At 8 weeks, quantitative and qualitative follow-up assessments were obtained. Measures included feasibility, acceptability, and preliminary data on efficacy. Qualitative data were transcribed verbatim, double coded, and interpreted using thematic analysis. Quantitative results were analyzed descriptively and with paired t tests. RESULTS: As planned, 16 participants (eight each gender) were recruited (75% of those who were eligible; 66% nonwhite, 63% low income, mean age 15.4). The intervention had high feasibility and acceptability: 93.8% completed 8-week follow-up; 80% of daily text messages received responses; 31% of participants requested ≥1 "on-demand" text message. In-person and text message portions were rated as good/excellent by 87%. Qualitatively, participants articulated: (1) iDOVE was welcome and helpful, if unexpected in the ED; (2) the daily text message mood assessment was "most important"; (3) content was "uplifting"; and (4) balancing intervention "relatability" and automation was challenging. Participants' mean ΔBDI-2 (Beck Depression Inventory) from baseline to 8-week follow-up was -4.9, (p = .02). CONCLUSIONS: This automated preventive text message intervention is acceptable and feasible. Qualitative data emphasize the importance of creating positive, relevant, and interactive digital health tools for adolescents.

Perceptibility and the "Choice Experience": User Sensory Perceptions and Experiences Inform Vaginal Prevention Product Design.

The development of pericoital (on demand) vaginal HIV prevention technologies remains a global health priority. Clinical trials to date have been challenged by nonadherence, leading to an inability to demonstrate product efficacy. The work here provides new methodology and results to begin to address this limitation. We created validated scales that allow users to characterize sensory perceptions and experiences when using vaginal gel formulations. In this study, we sought to understand the user sensory perceptions and experiences (USPEs) that characterize the preferred product experience for each participant. Two hundred four women evaluated four semisolid vaginal formulations using the USPE scales at four randomly ordered formulation evaluation visits. Women were asked to select their preferred formulation experience for HIV prevention among the four formulations evaluated. The scale scores on the Sex-associated USPE scales (e.g., Initial Penetration and Leakage) for each participant's selected formulation were used in a latent class model analysis. Four classes of preferred formulation experiences were identified. Sociodemographic and sexual history variables did not predict class membership; however, four specific scales were significantly related to class: Initial Penetration, Perceived Wetness, Messiness, and Leakage. The range of preferred user experiences represented by the scale scores creates a potential target range for product development, such that products that elicit scale scores that fall within the preferred range may be more acceptable, or tolerable, to the population under study. It is recommended that similar analyses should be conducted with other semisolid vaginal formulations, and in other cultures, to determine product property and development targets.

Psychometric Properties and Validity of a Multi-dimensional Risk Perception Scale Developed in the Context of a Microbicide Acceptability Study.

Currently available risk perception scales tend to focus on risk behaviors and overall risk (vs partner-specific risk). While these types of assessments may be useful in clinical contexts, they may be inadequate for understanding the relationship between sexual risk and motivations to engage in safer sex or one's willingness to use prevention products during a specific sexual encounter. We present the psychometric evaluation and validation of a scale that includes both general and specific dimensions of sexual risk perception. A one-time, audio computer-assisted self-interview was administered to 531 women aged 18-55 years. Items assessing sexual risk perceptions, both in general and in regards to a specific partner, were examined in the context of a larger study of willingness to use HIV/STD prevention products and preferences for specific product characteristics. Exploratory and confirmatory factor analyses yielded two subscales: general perceived risk and partner-specific perceived risk. Validity analyses demonstrated that the two subscales were related to many sociodemographic and relationship factors. We suggest that this risk perception scale may be useful in research settings where the outcomes of interest are related to motivations to use HIV and STD prevention products and/or product acceptability. Further, we provide specific guidance on how this risk perception scale might be utilized to understand such motivations with one or more specific partners.

Meaning-making matters in product design: users' sensory perceptions and experience evaluations of long-acting vaginal gels and intravaginal rings.

OBJECTIVE: Users' sensory perceptions and experiences of intravaginal products can inform acceptability and adherence. Focusing on the meanings women derive from formulation/device characteristics facilitates developers' design iterations toward optimizing user experience. We investigated how users of long-acting gels and intravaginal rings (IVRs) impute meaning to characteristics that may affect future product use. STUDY DESIGN: Focus groups were conducted with contraceptive IVR and vaginal lubricant users. Current perceptibility science and historical theory on the cultural acceptability of fertility regulating methods informed the analysis. RESULTS: A total of 21 IVR users and 29 lubricant users attended focus groups in which they manipulated products in their hands and discussed reactions to product characteristics. Participants used prior product experiences and sensory perceptions of prototype manipulations to inform meanings about product properties and performance for pregnancy, disease prevention, comfort, and perceived efficacy. The meanings derived from product characteristics depended on why the product would be used; a characteristic deemed problematic in one risk context may be considered preferable in another. CONCLUSIONS: Intravaginal product users create narratives that ascribe influence or causality to product characteristics. These meanings, whether correct or incorrect biologically, will shape vaginal product acceptability, use, and effectiveness. IMPLICATIONS: Long-acting and sustained-release drug delivery systems will be part of the multipurpose prevention continuum. Developers must consider how sensory experiences and culturally salient assumptions shape the meanings users make of product design characteristics. Those meanings will ultimately impact use and effectiveness.