Grace Kulik (née Ditzenberger), PT, DPT
Image credits: LinkedIn
Kristine M Erlandson, MD, MS
Image credits: LinkedIn
A new analysis from the PREPARE (Pitavastatin to REduce Physical Function Impairment and FRailty in HIV) trial found that 52% of middle-aged adults with HIV experienced measurable declines in physical function over time. Published in the June 2025 issue of Open Forum Infectious Diseases, the study highlights the importance of identifying individuals at risk for functional decline to support aging with HIV and prevent disability.
The analysis included 569 participants with HIV (median age 51 years; interquartile range, 47–55), 81% of whom were male and 52% White. Physical function was assessed annually using gait speed, chair rise rate, grip strength, and a modified Short Physical Performance Battery (SPPB), which also included balance time. Decline was defined as falling below the 20th percentile on at least one measure. While overall declines were modest, variability among individuals was considerable.
Demographic and clinical risk factors for decline included female sex (RR, 1.32; 95% CI, 1.12–1.55), non-White race (RR, 1.23; 95% CI, 1.05–1.45), and older age. In multivariable analyses adjusting for age, sex, and race, additional independent predictors included history of depression treatment, elevated body mass index (BMI), baseline frailty, and elevated inflammatory markers such as high-sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6).
To contextualize these findings, Contagion spoke with study authors Grace Kulik, PT, DPT, PhD candidate at the University of Colorado (UCD) Anschutz Medical Campus, and Kristine M Erlandson, MD, MS, professor of infectious diseases at UCD Anschutz about the clinical implications of functional decline in people with HIV (PWH), including the roles of inflammation, ART exposure, and screening in mitigating long-term impairment.
Contagion: How do systemic inflammatory markers such as high-sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6) specifically contribute to physical function decline in people with HIV, given the immune dysregulation associated with the infection?
Kulik: Higher levels of inflammatory markers are thought to contribute to muscle wasting, which in turn is thought to reduce physical function. Chronic inflammation has also been linked with reduced levels of overall physical activity, and low physical activity is strongly associated with poor physical function.
Contagion: Which infectious complications or HIV-related comorbidities most significantly exacerbate functional impairment, and what early monitoring strategies do you recommend?
What You need To Know
The PREPARE trial found that 52% of adults with HIV showed measurable declines in physical function, based on standard mobility and strength assessments.
Risk factors for decline included elevated hsCRP and IL-6, higher BMI, prior depression treatment, female sex, and non-White race.
Routine clinical screening using chair rise or gait speed tests can help identify early functional decline and guide timely interventions.
Kulik: Prior studies by Dr. Erlandson have demonstrated that physical function is negatively associated with the immune response to cytomegalovirus, which is a common co-infection among people with HIV, even if they have a suppressed viral load. HIV is associated with a greater risk for other comorbidities, such as cardiovascular disease and diabetes, which have also been linked to physical function impairment. Performing annual or semi-annual tests such as 4-meter gait speed, time to complete 5 or 10 chair rises, and grip strength tests are the most commonly used strategies to screen for physical function impairment. Personally, I think that the 4-meter gait speed or chair rise assessments are the most feasible to incorporate for clinical screening because grip strength requires additional equipment and calibration.
Contagion: From your clinical experience, how do antiretroviral therapy (ART) regimens impact physical function trajectories in aging individuals with HIV?
Erlandson: Some of the older therapies (AZT, DDI, D4T) can have a negative impact on skeletal muscle, mitochondrial function (in fat or skeletal muscle), and/or contribute to neuropathy. Efavirenz has also been linked to greater physical function decline, possibly through some of the neurocognitive or weight-suppressive effects. Obesity contributes to physical function decline, so we ultimately may see greater physical function declines in people with greater weight gain, regardless of the regimen.
Contagion: What role do you see for infectious disease specialists in multidisciplinary interventions aimed at preventing or mitigating physical decline in this population?
Erlandson: Many infectious disease specialists serve as the primary care providers for patients living with HIV. Infectious disease providers may see people with HIV frequently—especially older adults or those with more comorbidities—and have the opportunity to recognize early declines and to provide counseling on preventive measures to mitigate physical function declines. Infectious disease specialists may also recognize important side effects or drug interactions with HIV medications that might contribute to physical function impairments, such as protease inhibitors with some statins.