In this study, 30 older Latino adults with HIV aged 50 years and older were enrolled in a single arm trial to assess the feasibility and acceptability of the HOLA health promotion intervention and to identify preliminary intervention effects on cognitive functioning. The mean age at baseline was 61.7 (SD 6.0) years, and the sample was predominantly men (60%; n=18). Participants were assessed at 2 time points (baseline and 16 weeks post intervention) on measures of neurocognitive and psychosocial functioning. Blood samples were collected to assess biomarkers of cognition. Consistent with recommendations from biostatistical workgroups funded by National Institutes of Health (NIH) [12], this pilot study was not powered to test hypotheses. Participants were recruited from the Center for HIV and Research in Mental Health which serves as a consent to contact database, to efficiently and ethically contact eligible participants who receive HIV care at the University of Miami or Jackson Health System HIV Clinic [57].

Inclusion and exclusion criteria for study participation are outlined in Textbox 1.

Notably, the age of 50 years was chosen as a cutoff for 2 reasons. First, more than half of individuals affected by HIV in the United States are aged 50 years or older [2]. Second, in HIV infection, patients aged 50 years and older have poorer immunological response to ART and poorer survival. This age has been used to define medically advanced age in HIV-infected people [58]. Because of the longitudinal study design, participants planning to move outside of the South Florida metropolitan area within 6 months of enrollment or not living in stable housing (eg, group home) were excluded. All participants read and signed an informed consent form approved by the University of Miami institutional review board (IRB).

Table 1 describes the measurement battery and assessment schedule.

The neurocognitive battery represents the domains that are used to classify cognitive impairment. These cognitive performance tests are norm-based, allowing us to detect performance comparisons to one’s age and education level. Multiple equivalent versions of these tests are available which reduces the potential confound of practice effects. Study measures were administered in either English or Spanish (using certified translations), according to the participant’s preference. Trained bilingual research assistants (RAs) conducted all assessments in private offices at the University of Miami or Jackson Health System HIV Clinic. A licensed neuropsychologist trained and supervised the RAs using a multistep process. First, the training focused on understanding test administration procedures, scoring guidelines, and potential difficulties of the specific tests that were to be administered. Second, the RAs observed the neuropsychologist administer the assessment battery. The RAs then practiced administering the test under direct supervision before transitioning to conducting the assessments on their own. The neuropsychologist would conduct interreliability checks and provide regular feedback and address any errors.

At the end of the intervention, participants’ satisfaction with the intervention was measured using the 8-item Client Satisfaction Questionnaire-8 [75]. At the end of the Client Satisfaction Questionnaire-8, there are 2 open-ended questions that allow participants to state in their own words what they liked most about the intervention and what they liked the least. Answers to these questions will be used to identify modifications needed in the design of a larger, ensuing hypothesis testing study.

Blood draws took place at the University of Miami or Jackson Health System HIV Clinic prior to starting baseline assessments. Approximately 20 mL (2 tablespoons) of blood was collected by a trained phlebotomist at both time points to assay biomarkers of cognition: myokines or cytokines (IL-15), adipokines (irisin and adiponectin), and neurotrophic factors (BDNF, IGF-1, and VEGF). APOE status, a genetic marker of dementia risk, was collected at baseline only. The biomarkers were assayed at the University of Miami Center for AIDS Research Laboratory Sciences Core using a commercially available enzyme-linked immunosorbent assay.

HOLA is a multicomponent health promotion intervention for older Latino adults. The first component consists of 2 manualized social and physical activation sessions. Prior to beginning the group walk phase, each participant met individually with a CHW for a 30-minute physical and social activation session to (1) educate participants about the goals of the intervention; (2) provide information surrounding cognitive functioning, age-related memory loss versus dementia, how their comorbidities impact cognition, and ways they can prevent cognitive decline; (3) motivate participants to engage in physical activity; (4) increase participants’ social activities; (5) identify potential obstacles that may interfere with meeting the demands of the intervention; and (6) brainstorm ways to overcome these obstacles. Participants met again individually with the CHW for 30 minutes after week 8 to discuss progress of physical and social activity goals. These meetings were typically held in the participants’ homes.

HOLA’s second component is a group walk, led by a CHW for 45 minutes, 3 times a week, for 16 weeks. Walks were conducted with a group of 6 participants at a centrally located public park. Each walk began with 10 minutes of stretching and warm up and followed by 25 minutes of moderately intense walking. The group walk concluded with a 10-minute cooldown phase of stretching.

The third component consists of scheduling pleasant events, which offers a means to generalize the intervention into the participants’ everyday lives and relationships. During the cool-down phase of each walking session, the CHW asks each participant to identify a pleasant event that they intended to do with another person before the next meeting. Subsequent sessions start with participants reporting on how effectively they implemented their pleasant event plan while the CHW and the group provided positive reinforcement and feedback.

Cultural values and beliefs were included in the formative phases of HOLA to ensure that it addressed sociocultural influences that have a role in the health of older Latino adults. First, recruitment, intervention, and assessment materials were available in English and Spanish, and we added further cultural components to the social and physical activation manual by including Latino relevant metaphors, values, and cultural proverbs (dichos). Second, our recruitment strategies focused on relationship building given the fear, mistrust, and stigmatizing attitudes in the Latino community toward participation in clinical research. Specifically, we emphasized the Latino cultural values of personalismo (the cultural value that emphasizes social relationships and the mutual respect that those in the relationship have for one another) and confianza (trust and familiarity). Third is the use of CHWs. Since CHWs possess an intimate understanding of the community, they understand cultural values and norms and know how to incorporate them in order to promote health and health outcomes. Moreover, older Latino adults with HIV may feel more comfortable divulging personal information to someone from their own community, allowing them to communicate with study personnel in their preferred language and in a manner in which they feel comfortable.

The CHW in this study worked on a previous HOLA trial [76] and was already trained to deliver the HOLA intervention using a detailed manual of operations. A clinical psychologist met weekly with the CHW to provide supervision and give one-on-one corrective feedback as needed to ensure that what was being delivered was fully consistent with the intervention as designed. Furthermore, all planned and unplanned contacts were recorded. This involved the CHW documenting the following variables for each contact with a participant: date, duration, type of session, initiator of contact, planned or unplanned contact, reason for contact, and activities engaged in.

For this pilot study, we evaluated the feasibility of recruitment, assessment procedures, retention, acceptability, and implementation of HOLA in a sample of older Latino adults with HIV (aim 1). Consistent with recommendations from biostatistical workgroups funded by NIH [39], this pilot study was not powered to test a hypothesis; therefore, we did not complete a power analysis. Successful recruitment was defined as meeting 100% of the targeted sample (N=30), with 20% (n=6) or less of eligible participants refusing to participate. Adequate retention was defined as 85% (n=25) or more of randomized participants completing the postintervention assessment, and acceptability was defined as 80% (n=38) or more of sessions attended by participants.

To explore changes in neurocognitive impairment (memory, reasoning or executive functioning, speed of processing; aim 2), and general activity, psychosocial functioning, and biomarkers of cognition (aim 3), a 1-way ANOVA will be used to illustrate the change in scores from baseline to postintervention in all the outcome measures. General linear modeling will be used to explore whether changes in psychosocial functioning or cognitive biomarkers (myokines or cytokines [IL-15], adipokines [irisin and adiponectin] and neurotrophic factors [BDNF, IGF-1, and VEGF]) correlate with changes in cognition, while accounting for genetic risk for dementia (APOE ε4 carrier status). Due to the small sample size, APOE genotypes will be collapsed into ε4 carrier status carriers and non-ε4 carriers (aim 4).

Given that depression and cognitive functioning are closely linked, it is possible that improvements in cognitive functioning could be due to reductions in depressive symptoms. Therefore, to understand better the intervention effect on cognitive functioning, we will use generalized estimating equation with a log link function and Poisson distribution. The model will estimate the incident rate ratio for cognitive functioning outcomes at follow-up versus baseline. All generalized estimating equation models will include time as the main effect and control for gender, age, socioeconomic status, years of education, and depression severity at baseline as covariates. In addition, a mediational analysis will be done using structural equation models to determine whether intervention effects, if detected, are influenced by depression.

Approval from the University of Miami IRB was obtained on May 14, 2021 (IRB ID 20201202). In addition, the trial was registered in the ClinicalTrials.gov database on March 5, 2021 (NCT04791709). All study procedures were conducted according to good clinical practice and all other relevant regulatory guidelines. Participants were informed that they may end their participation in the study at any time without affecting access to any other services they were receiving. Participant payments were graduated such that participants received US $25 on the baseline visit and US $35 on the follow-up visit (total honoraria: US $60). They also got to keep the tracking device.

Completed data were entered into password secured databases by authorized staff. All electronic data were deidentified and stored in password-protected files on servers at the University of Miami Miller School of Medicine Department of Psychiatry and Behavioral Sciences. For each data file, a code number was assigned, and the master list, linking code numbers with names, was stored separately. At the conclusion of the project, the record linking the assigned research number and participant identity will be destroyed. No participant will be identified within any published report. Each member of the research team was certified and trained in maintenance of confidentiality and data compliance standards.

To the best of our knowledge, this is the first study to adapt a culturally tailored health promotion intervention for older Latino adults with HIV to improve physical, mental, and cognitive health. Findings from this pilot study will help to identify whether the HOLA health promotion intervention is (1) feasible and acceptable to a group of older Latino adults with HIV, and (2) potentially efficacious in bolstering brain health in this underserved group. Encouraging findings from this exploratory study may provide a blueprint for scaling up HOLA to a larger cohort of older Latino adults with HIV who may be currently experiencing or at risk for HIV-related cognitive challenges.

There are several benefits to this single arm pilot trial. At the individual level, older Latino adults with HIV may acquire and practice health behaviors that lead to improved well-being by participating in this intervention. Similarly, engaging with this intervention offers older Latino adults with HIV the opportunity to receive support, advice, encouragement, and feedback from a trained CHW and other participants who are peers with similar lived experiences as themselves. Continued psychoeducation on physical, mental, and cognitive health from the CHW as well as emotional, instrumental, informational, and appraisal support from peers may help participants gain enhanced motivation to take control of their health while also increasing psychological well-being and self-efficacy.

This project has direct public health implications at the societal level. Findings from this research may offer insight into how a health promotion intervention could improve cognitive functioning among older Latino adults with HIV with implications for dementia prevention. Similarly, older Latino adults, particularly those with HIV, are at increased risk for developing depression and anxiety compared to their White age-matched peers. Therefore, based on the intervention’s focus on facilitating activity and increasing social support among older Latino adults with HIV, HOLA may chip away at social isolation among participants through opportunities for socialization and relationship-building with peers, leading to general mental health improvements in the long-term. In addition to improving the general well-being of older Latino adults with HIV, the development of more efficacious interventions that stave off cognitive and mental health challenges prior to their onset among this group is cost-effective and reduces future health care burden costs. Ultimately, approaches such as the HOLA intervention shift the attention toward preventing morbidity rather than treating it.

Finally, this study is highly relevant and responsive to the NIH priority to “maintain or improve the cognitive performance of all adults,” especially for those “populations experiencing the greatest disparities and risks in cognitive health” [77]. This project shares the same values as both the NIH Cognitive and Emotional Health Project and the Healthy Brain Initiative (a national road map to maintaining cognitive health) and offers a noninvasive technique to improve cognition in adults with HIV, a major challenge currently facing the field [17].

This study has some limitations. First, it targeted older Latino adults with HIV living in the southeastern United States; therefore, study findings may not be generalizable to older Latino adults with HIV living in other parts of the United States or globally. Second, participants were older Latino adults with HIV who were engaged in HIV care and living who have a suppressed HIV viral load. In order to support older Latino adults with an unsuppressed HIV viral load, this intervention may need to be tailored to accommodate them. Third, participants who were not living in stable housing were excluded from the study. Including participants who were not living in stable housing—which typically make up a fairly large portion of people living with HIV—would have provided interesting and useful information about whether they would have been able to attend the intervention and how they would have fared in the study. However, given that we only had 1 year to recruit 30 participants and run them through a 16-week intervention, we had to make the most efficient use of our time. Therefore, the decision was made to only include participants who were stably housed. We intend to remove this criterion in a subsequent, adequately powered trial. Fourth, the study was not powered to test for intervention effects. However, any effects that are found to be statistically significant would be encouraging. Nonetheless, this single-arm pilot study used a sound methodological approach, and, if successful, data gleaned will advance the field of HIV-related cognitive impairment among older Latino adults with HIV.