Trial design
This was a pilot, parallel design, two-arm RCT that recruited people aging with HIV who had been diagnosed with mild-to-moderate HAND from a neurobehavioural research centre at a tertiary care hospital in Toronto, Canada. This trial was designed using a refinement framework32 to assess whether a trial of this nature could be upscaled and, if so, what the key considerations (i.e., participants, design, interventions, outcomes) would be for that larger study. Community-based participatory research guided this trial’s design as a team of ten people aging with HIV and concerned about HAND were consulted in intervention selection, questionnaire design, and eligibility and recruitment considerations. Further, people aging with HIV were staff facilitators on both intervention arms. The study protocol has been published elsewhere33. No changes were made from protocol to completion.
Participants
People living with HIV were eligible to participate in this study if they were at least forty years of age, had a documented diagnosis of mild-to-moderate HAND from the recruiting neurobehavioural clinic, had last clinic visit after 1 January 2016, had been living with HIV for five years or more, consented to be contacted by the recruiting clinic for further research, and could commit to eight weekly sessions of group therapy in downtown Toronto. Participants were excluded from participation if their HAND diagnosis was asymptomatic or severe, if they had been admitted to a hospital in the past month, if they were unable to communicate in English, if they were unable to use a tablet for brain training activities, or if the research coordinator assessed that they would be disruptive in group therapy (e.g., if they made discriminatory comments). These criteria were set to precipitate a comfortable group atmosphere where participants may share a similar level of cognitive impairment while having progressed past the initial concerns of a recent HIV diagnosis.
Interventions
The novel and control arms both contained a form of group therapy that was comprised of a 3-hour orientation session and eight 3-hour weekly group sessions in downtown Toronto, Canada.
Cognitive remediation group therapy (novel arm)
The novel arm of cognitive remediation group therapy (CRGT) was held at the Centre for Mindfulness Studies in Toronto and blended mindfulness-based stress reduction (MBSR) and brain training activities (BTA). Each weekly session was divided as two hours of manualized MBSR facilitated by a physician and a social worker followed by one hour of BTA facilitated by a peer aging with HIV. For the BTA component, participants were provided with access to a Samsung tablet and a 1-year license to BrainHQ training by PositScience. As BTA has predominantly been administered as a passive, individual exercise where a participant is given the software and written instructions for use with minimal follow-up25, a participatory approach was required to incorporate BTA into active group therapy. The BTA facilitator sought participant feedback on how to structure this component of CRGT; the decision was to have forty minutes of group discussion on training progress and challenges with twenty minutes dedicated to individual practice and troubleshooting of software features.
Mutual aid group therapy (control arm)
The control arm of mutual aid group therapy was held at the AIDS Committee of Toronto and was facilitated by a social worker and a peer aging with HIV. The facilitators followed the intervention’s manual33 of maintaining safety in the group while encouraging participants to share their experiences living with HIV-related cognitive impairment and associated coping strategies with one another. Facilitators of this model attempt to create connections between participants by identifying commonalities in their experiences with the aim of creating a community of people within the group that can support one another through shared challenges.
Outcomes
Feasibility was assessed against a priori targets that the research team agreed would be necessary to proceed with a larger trial, based on relevant literature34,35 and the team’s experience with piloting and implementing interventions of this nature36,37. The targets, based on a sampling frame of forty people, were: 30% of those contacted agreed to participate, 25% completed the initial assessment, 20% attended the first orientation session of their treatment arm, 16% completed their entire arm’s group series the final 3-month follow-up assessment.
Acceptability was measured via a satisfaction questionnaire conducted at the midpoint and endpoint of each arm’s group therapy series. The questionnaire consisted of the Likert-style Helping Characteristics of Self-Help and Support Groups Measure38 (22-items, α = 0.87) and open-ended questions about session length, number of sessions, activities used, and evaluation of facilitators that the researchers have used in previous pilot intervention studies.
For intervention fidelity, facilitators of both trial arms submitted weekly session reports that were comprised of checklists of therapy components and open-ended questions about activities completed in each group, dynamics between participants, and challenges of facilitation. An a priori target of a minimum of 80% of checklist therapy components per session was set, based on prior fidelity research39.
Exploratory outcomes of stress, anxiety, coping, use of mindfulness strategies, and use of brain training activities were assessed at three times: preintervention, postintervention, and 3-month follow-up. Standardized measures used were: HIV/AIDS Stress Scale40 (29-items, Likert, α =0.91), Anxiety in Cognitive Impairment and Dementia Scale41 (26-items, dyadic, α =0.87), Coping Self-Efficacy Scale of Health Problems42 (10-items, Likert, α =0.85, and the Five Facet Mindfulness Questionnaire–Short Form43 (24-items, α =0.80).
Sample size
Twelve to sixteen participants was chosen as the numbers necessary to initiate this pilot RCT as: a) that would permit six to eight people in each trial arm, which is ideal for group therapy of this nature44; and b) similar numbers have been used to assess other pilot group therapy studies31,37.
Randomization
A research coordinator enrolled participants by confirming their eligibility, attaining their informed consent, and collecting their availability for group therapy. Concealed allocation was then employed, whereby the first author provided the study sponsor with unique identifiers for each enrolled person and the sponsor then randomized participants in a 1:1 fashion using size two blocks to either the novel or control arm. These results were then communicated individually to each participant, alongside details regarding the schedule of their group therapy series.
Blinding
Intervention facilitators were blind to outcome assessments, which were conducted by a research coordinator. Participants in one arm were blind to participants in the other arm. Analysts were blind to participant identities. Participants were not blinded regarding the content of each arm, as the research coordinator discussed the two arms that participants could be assigned to when attaining their informed consent. The similarity of interventions – that they were both group therapies with one more focused on discussion (control) and the other on mindfulness and brain training (novel) – was described.
Data Analysis
For feasibility, proportions of participant recruitment, enrolment, and completion were calculated. Acceptability was analyzed through a spaghetti plot showing individual results of the satisfaction measure and reasons for participant withdrawal were also described. Fidelity was analyzed by tabulating intervention checklist items and qualitatively by two independent coders trained in the intervention models who employed content analysis for the open-ended responses to determine if interventions were delivered as designed. Exploratory outcomes were also analyzed through spaghetti plots show individual progress on these assessments, complemented by non-parametric Wilcoxon rank sum tests run in R 3.5.1 (Feather Spray) to determine if there was a significant between group difference for change in outcomes relative to preintervention. As the team could not find a standardized scale to assess BTA use at the time of study design, progress reports from PositScience by BrainHQ were used for the novel arm and self-reported use of BTA was used for the control arm.