In this cross-sectional study we compare physical function of HIV-infected patients to uninfected patients who are demographically similar and under care in the same medical system. The baseline function score, based on patient reported ability to perform a range of physical activities, correlates with the established SF-12 physical subscale, and is associated with differential survival. The majority of patients in this clinic-based cohort are 50 years of age and older in both patients groups, a frequently used benchmark to designate older HIV-infected adults. This opportunity allowed us to investigate the relationship of age and function with comorbidity between HIV-infected and uninfected patients.
Within the limits of a cross-sectional study, the difference in function between younger and older patients was greater in HIV-infected patients compared to the uninfected patients, adjusted for comorbidity. The magnitude of the rate of decline in function across the age groups was greater in the HIV-infected patients. In both the 50–54 and 55
age groups physical function was worse in the HIV-infected patients. These results are supported by exercise performance testing that shows significantly lower aerobic capacity among older HIV-infected patients compared to age-matched uninfected adults.28
It should be noted in the younger (age
44 years) age group that HIV-infected patients reported higher function than uninfected patients. Only this age group of HIV-infected patients had similar frequency of exercise compared to the uninfected patients. This finding raises the question of the role of physical inactivity in worse physical function among older HIV-infected patients.
In the general medical literature, poor physical function is strongly associated with cardiovascular disease (CVD), including coronary artery disease, congestive heart failure, peripheral vascular disease, and stoke.12,13,15,16
For all of these conditions we found a significant independent association with function in HIV-infected patients that was similar to uninfected patients. Given that HIV-infected patients may have increased risk of coronary heart disease and cardiac dysfunction,1,3,29
CVD will likely become a significant source of physical disability in HIV-infected patients who are otherwise stable on cART, and thus provides additional incentive to reduce cardiac risk factors.4
Although none of the CVD conditions in our study were associated with worse function in HIV-infected patients compared to uninfected patients, our function scale may be unable to distinguish these differences given the scale's ceiling effect. In addition, self-report in general may be limited in its capacity to measure specific functional performance parameters, such as endurance, which are related to cardiovascular disease. For instance, exercise treadmill testing has shown that aerobic capacity is reduced 16% in older HIV-infected men with hypertension compared to those without hypertension.30
Further research is needed to investigate the specific mechanisms underlying poor function for different types of CVD, and whether differences exist between HIV-infected and uninfected patients.
In contrast, the VACS function score clearly showed an additive effect of chronic obstructive lung disease and HIV on physical function. The results were consistent across the age groups with adjustment for other comorbid conditions and smoking history. Chronic pulmonary disease is independently related to functional limitations in uninfected adults,31,32
and may occur more frequently in HIV-infected adults.5–7
Our results suggest that among those with chronic obstructive lung disease, HIV-infected patients have worse physical function compared to uninfected patients. However, conclusions should be tempered given the lack of information on lung function. Physical function in HIV-infected patients among those with chronic pulmonary disease could be worse due to either accelerated progression33
or longer duration of lung disease. A third possibility is a confounding factor related to both chronic pulmonary disease and function. Recent research shows that the adjusted risk of lung cancer, pulmonary hypertension and pulmonary fibrosis is greater in HIV-infected compared to uninfected patients.6
Although these conditions may be less common, they are associated with chronic lung disease and were not considered in our analyses. While understanding these mechanisms is beyond the scope of this study, the results support an HIV aging interaction driven by comorbidity that warrants further investigation. With regard to HIV care, this finding supports the importance of smoking cessation.24,34
Finally, the contrasting results for BMI and diabetes in HIV-infected versus uninfected patients highlights the challenge of differentiating effects of medication, HIV infection, and aging. HIV-infected patients classified as obese by BMI likely represent a heterogeneous group, which includes those experiencing a restoration to health phenomenon that comes with successful antiretroviral therapy. This supposition is supported by the Nutrition for Healthy Living study, a prospective longitudinal study that showed that HIV-infected men with a five kilogram or larger increase in total body weight reported improvement in physical function.26
Importantly, HIV-infected individuals have experienced the effects of obesity for a shorter period of time than uninfected subjects since they were likely thinner prior to receiving cART treatment. The attenuated negative association of diabetes with function in the HIV-infected group supports this possibility. However, our findings are limited without data on duration or severity of diabetes, and need to be investigated further. In addition, anthropometrics may provide information that is missed by measure of BMI alone.35
Our findings confirm that advanced HIV disease is associated with worse physical function. However, in comparison to earlier studies which focused on the effect of AIDS on function,17
the majority of HIV-infected VACS participants receive cART and have high CD4 cell counts. Our findings demonstrate that age-related comorbidity should be considered an important risk factor for poor physical function in this clinical setting. For example, history of congestive heart failure is independently associated with a 10-point lower function score, compared to a low CD4 cell count (<200 cells/cm3
), which is associated with a 3-point lower score. Unlike our preliminary study,20
in this larger cohort with over 1450 patients with hepatitis C infection, the relationship between hepatitis C and function was similar in HIV-infected and uninfected patients (). The absence of a significant interaction was confirmed in the full multivariable model (HIV*HCV ßcoeff
0.1). However, further work is needed to investigate this relationship as we defined hepatitis C infection by ICD-9 code and did not differentiate cases by ongoing viral replication, nor severity of liver disease.
The primary limitation of the study is related to the cross-sectional design. We report a decline in function with age that that compares individuals at different ages, not a within-person difference in rate of decline. Therefore, findings could reflect selection or cohort effects, and require confirmation in longitudinal analysis. An additional limitation is the definition of comorbid conditions by history only, without data on disease severity and duration. While most cross-sectional studies are limited to prevalent cases, it is possible that duration and severity of some comorbid conditions may be greater in HIV-infected patients and then translate to worse function. Self-reported limitations in physical activities allow for measure of function within the social context, but can be affected by reporting bias. This may be evident given the large proportion of patients that denied any physical limitations. Although this ceiling effect is very similar to a survey study on function in community dwelling HIV-infected patients,26
it limits the ability to investigate higher level of functioning. While the study results are subject to these limitations in terms of causal inference, they provide important direction for future research in aging and physical function.
In summary, age-associated comorbidity affects physical function in HIV-infected patients. Longitudinal research with measure of disease incidence and severity is needed to determine if there is an accelerated loss of function with aging. However, our results highlight the potential role of comorbidity as an effect modifier in the relationship of HIV and aging. The study supports further integration of primary health care and prevention into HIV care with increased focus on age-associated comorbidity.36