Grace Kulik (née Ditzenberger), PT, DPT
Image credits: LinkedIn
A new analysis from the PREPARE (Pitavastatin to REduce Physical Function Impairment and FRailty in HIV) trial found that more than half (52%) of middle-aged adults with HIV experienced measurable declines in physical function over time. In the June 2025 issue of Open Forum Infectious Diseases, the findings underscore the importance of early identification of individuals at risk for functional decline. As the population of people with HIV (PWH) continues to age, the results support the need for targeted clinical interventions to help preserve physical function and prevent disability.
The study evaluated 569 participants with HIV, of whom 81% were male and 52% were White, with a median age of 51 years (IQR, 47–55). Researchers assessed physical function annually using gait speed, chair rise rate, grip strength, and a modified Short Physical Performance Battery (SPPB) that also included balance time. Decline in physical function was defined as scoring below the 20th percentile on at least one of these measures. While the overall average decline was small, individual variability was substantial.
Several demographic and clinical factors were associated with a higher risk of physical function decline. Female participants were more likely to experience decline compared to males (relative risk (RR), 1.32; 95% CI, 1.12–1.55), as were non-White individuals (RR, 1.23; 95% CI, 1.05–1.45). Risk increased with age: participants aged 55 years and older had a higher, though not statistically significant, risk of decline compared with those under 50 (RR, 1.17; 95% CI, 0.98–1.39).
In multivariable models adjusted for age, sex, and race, several baseline factors were independently associated with functional decline. These included history of depression treatment, higher body mass index (BMI), preexisting functional impairments, frailty as measured by a frailty index, and elevated levels of inflammatory markers such as high-sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6).
In an expert Q&A, Contagion spoke with author Grace Kulik, PT, DPT, a PhD candidate at the University of Colorado Anschutz Medical Campus, to better understand the risk factors for physical function decline in people with HIV (PWH). She discusses the roles of inflammation, ART regimens, and infectious disease clinicians in recognizing and managing physical impairment in this population.
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?
Kulik: 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?
Kulik: 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.