The goal of this HIV and Aging Pilot Program Proposal is to foster interdisciplinary collaborations in HIV and geroscience by providing emerging researchers with experience and mentorship in translational research. The focus is on collecting data on the efficacy and feasibility of short-term high-intensity interval training among older people with HIV (PWH) and co-occurring hypertension.

Non-AIDS defining comorbidities are increasingly prevalent among aging PWH. The use of antiretroviral therapies (ART) has extended life expectancy, presenting unique risks for aging-related multimorbidities. Hypertension, affecting over 50% of HIV-infected adults in the U.S., is a significant chronic disorder among PWH. Regular exercise improves function and prevents decline in adults with comorbidities. Functional outcomes are good predictors of cardiovascular health in older PWH with hypertension. Exercise improves cardiovascular, metabolic, and functional measures in young PWH, but older PWH often do not meet physical activity guidelines due to barriers like motivation, time, and pain.

The impact of high-intensity exercise on physical function in older PWH is unknown, despite evidence of benefits from low-moderate intensity exercise. Assessing the feasibility and acceptability of high-intensity exercise in older PWH with hypertension will provide valuable information for future studies.

The specific aims of the proposed study are to assess the integrity of the study protocol, including safety, adherence, and retention, to develop standard operating procedures for future trials, while determining participant perceived benefits and barriers. Additionally, the study aims to assess the variance of secondary outcomes and the effects of the intervention on the 6-minute walk test, lower extremity function as assessed by the Short Physical Performance Battery, skeletal muscle strength and endurance as assessed by isokinetic muscle testing, chronic pain evaluated by the Brief Pain Inventory and Pain assessments, markers of vascular health such as arterial stiffness, and circulating indices of inflammation including inflammatory profile, skeletal muscle degradation, and metabolism.

Life expectancy for people with HIV (PWH) has increased in the antiretroviral therapy (ART) era and shifted the demography of the HIV epidemic toward the aging population. By the year 2030, an estimated 70% of PWH in the United States will be at least 50 years of age, thus implicating age-related comorbidities as a potential challenge for PWH. In particular, hypertension represents a major co-morbidity burden among PWH. Regular physical activity improves function in adult populations with comorbidities and prevents functional declines.

Maintenance of functional status, determined by measures of physical performance, is a good predictor of cardiovascular outcomes among older PWH with co-occurring hypertension. Exercise is the only intervention with evidence to support its use in treating age-related functional declines. Exercise is a strategy employed by PWH and rehabilitation professionals to address the functional decline and improve the health and quality of life of those individuals. Exercise interventions in PWH support the evidence that exercise can improve cardiovascular, metabolic, and functional measures in younger PWH. Though meeting the recommended guidelines for regular physical activity in older adults is feasible, the repercussions of high-intensity interval training in improving physical function are unknown despite evidence displaying functional improvements following low and moderate-intensity interventions.

While many exercise studies have reflected the benefit of six to twelve weeks of exercise, many report that the results are limited to the participants who are motivated with good compliance and completion profiles. In real-world situations, adherence to exercise, particularly high-intensity exercise, may fall below desirable levels and hinder the effectiveness of the programs. This may be due, in part, to perceived benefits and barriers to exercise in older PWH. Despite the growing body of research aimed at determinants of adherence to pharmaceutical treatment, adherence to exercise among PWH remains an under-researched area.

The purpose here is to evaluate the efficacy and efficacy of a high-intensity interval training intervention for improving the physical function of older PWH and co-occurring hypertension. The central hypothesis is that high-intensity exercise will improve functional decrements of older PWH. An evaluation of high-intensity interval training in PWH may be important as this population has impairment in functional outcomes compared with age-matched uninfected controls, with even greater impairments among older PWH. Underlying inflammation, pain, and skeletal muscle degradation related to HIV suggest that older PWH may require higher doses of exercise to restore or achieve levels of physical function. Thus, the objective of this pilot application is to evaluate the efficacy and feasibility of short-term high-intensity interval training among 15-20 older PWH > 50 years with co-occurring hypertension, recruited from CNICS. To achieve this objective, the investigators propose to conduct a pilot study to address the following specific aims, which are crucial to designing future studies:

Specific Aim 1: To assess the integrity of the study protocol, including safety, adherence to the interventions, and retention to study visits, in order to develop standard operating procedures for guidance of a future trial. Additionally the investigators will determine participant perceived benefits and barriers, assessed by the Exercise Benefits and Barriers Scale.

Specific Aim 2: To assess the variance of secondary outcomes and effects of the intervention on outcomes including 1) 6-minute walk test, 2) lower extremity function, assessed by the Short Physical Performance Battery (SPPB), 3) skeletal muscle strength and endurance, assessed by isokinetic muscle testing, 4) chronic pain, evaluated by the Brief Pain Inventory and Pain assessments, 5) markers of vascular health (e.g., arterial stiffness), 6) circulating indices of inflammation (e.g. inflammatory profile [IL-1β, TNF-α, IL-6, CRP, IL-8, IL-10], skeletal muscle degradation [creatine kinase], and metabolism [fasting glucose, HA1C, lactate, and fasting cholesterol].

Inclusion Criteria:

• >= 50 years of age at study entry
• must be on ART regimen
• Inactive Lifestyle (<150 minutes per week of moderate activity on CHAMPS Questionnaire)
• CD4 T-cell count greater than 200 cell/mm^3 (
• Hypertensive (untreated SBP >=130mmHg or DBP >=80 mmHg)
• Functional limitations inhibiting the ability to exercise.

Exclusion Criteria:

• BP >140/90 despite the use of 4+ antihypertensive medications
• chronic kidney disease
• severe cardiac condition (CHF, stenosis, history of cardiac arrest, defibrillator, angina)
• Ischemic heart disease
• self reported >= 90 days of daily opioid use
• Beta Blocker Significant cognitive impairment

These data are very preliminary and thus exploratory in nature. This was used to build a larger intervention. However, should researchers request information, we will disseminate IPD as deemed necessary.