Catherine M. Jankowski

Association of Functional Impairment with Inflammation and Immune Activation in HIV Type 1–Infected Adults Receiving Effective Antiretroviral Therapy

BACKGROUND The relationships of inflammation, immune activation, and immunosenescence markers with functional impairment in aging human immunodeficiency virus type 1 (HIV-1)-infected persons are unknown. METHODS HIV-infected persons who were aged 45-65 years, had a plasma HIV-1 RNA load of <48 copies/mL, and were receiving antiretroviral therapy underwent standardized functional testing. In a nested case-control analysis, low-functioning cases were matched (1:1-2) by age, sex, and HIV-1 diagnosis date to high-functioning controls. Markers of inflammation, T-cell activation, microbial translocation, immunosenescence, and immune recovery were used to estimate functional status in conditional logistic regression. Primary analyses were adjusted for CD4(+) T-cell count, smoking, and hepatitis. RESULTS Thirty-one low-functioning cases were compared to 49 high-functioning controls. After statistical adjustment, lower proportions of CD4(+) T cells and higher proportion of CD8(+) T cells, higher CD38/HLA-DR expression on CD8(+) T cells, and higher interleukin-6 were associated with a significantly greater odds of low functional status (odds ratio, ≥ 1.1 for all analyses; P ≤ .03). Other inflammatory, senescence, and microbial translocation markers were not significantly different (P ≥ .11 for all analyses) between low-functioning and high-functioning groups. CONCLUSIONS Functional impairment during successful antiretroviral therapy was associated with higher CD8(+) T-cell activation and interleukin 6 levels. Interventions to decrease immune activation and inflammation should be evaluated for their effects on physical function and frailty.

Risk factors for falls in HIV-infected persons

Background:The incidence of and risk factors for falls in HIV-1–infected persons are unknown. Methods:Fall history during the prior 12 months, medical diagnoses, and functional assessments were collected on HIV-infected persons 45–65 years of age receiving effective antiretroviral therapy. Fall risk was evaluated using univariate and multivariate regression analyses. Results:Of 359 subjects, 250 persons (70%) reported no falls, 109 (30%) had ≥1 fall; and 66 (18%) were recurrent fallers. Females, whites, and smokers were more likely to be recurrent fallers (P ⩽ 0.05). HIV-related characteristics including current and nadir CD4 T-cell count, estimated HIV duration, and Veterans Aging Cohort Study Index scores were not predictors of falls (all P ≥ 0.09); didanosine recipients were more likely to be recurrent fallers (P = 0.04). The odds of falling increased 1.7 for each comorbidity and 1.4 for each medication (P < 0.001) and were higher in persons with cardiovascular disease, hypertension, dementia, neuropathy, arthritis, chronic pain, psychiatric disease, frailty, or disability [all odds ratio (OR) ≥ 1.8; P ⩽ 0.05]. Beta-blockers, antidepressants, antipsychotics, sedatives, and opiates were independently associated with falling (all OR ≥ 2.7; P ⩽ 0.01). Female gender, diabetes, antidepressants, sedatives, opiates, didanosine, exhaustion, weight loss, and difficulty with balance were the most significant predictors of falls in logistic regression (all OR ≥ 2.5; P ⩽ 0.05). Conclusions:Middle-aged HIV-infected adults have high fall risk. Multiple comorbidities, medications, and functional impairment were predictive of falls, but surrogate markers of HIV infection or an HIV-specific multimorbidity index were not. Fall risk should be assessed routinely as part of the care of HIV-infected persons.

Functional impairment is associated with low bone and muscle mass among persons aging with HIV infection.

Background:Disability and frailty are associated with osteoporosis, obesity, and sarcopenia. HIV-infected persons have early functional impairment, but the association between body composition and functional impairment is unknown. Methods:HIV-1–infected participants on combination antiretroviral therapy with virologic suppression, aged 45–65 years, had standardized physical function measures. In a nested analysis, 30 low- and 48 high-functioning cases and controls were matched by age, gender, and time since HIV diagnosis. Bone mineral density, fat mass, and lean body mass were assessed by dual-energy x-ray absorptiometry. Odds ratios (ORs) with 95% confidence intervals were obtained from conditional logistic regression. Results:Mean age was 53 years, mean CD4+ lymphocytes 598 cells per microliter, and 96% had plasma HIV-1 RNA <50 copies per milliliter. Low- and high-function subjects had similar CD4+ lymphocyte count and duration and type of antiretroviral therapy. Lower T scores at the hip [OR: 3.8 (1.1 to 12.5)] and lumbar spine [OR: 2.3 (1.1 to 4.5)] and lower lean body mass [OR: 1.1 (1.0 to 1.2)] were associated with significantly greater odds of low function (P ⩽ 0.03). Lower insulin-like growth hormone [IGF-1; OR: 5.0 (1.4 to 20.0)] and IGF-1 binding protein-3 [OR: 3.3 (1.7 to 9.9)] increased the odds of low functional status (P ⩽ 0.02). Fat mass and lower 25-OH vitamin D did not increase the odds of low functional status (P > 0.05). Conclusions:Functional impairment in HIV-1–infected persons on successful antiretroviral therapy is associated with low muscle mass, low bone mineral density, and low IGF-1 and IGF-1 binding protein-3. These characteristics may be a manifestation of early “somatopause” in middle-aged HIV-infected adults.

Functional impairment, disability, and frailty in adults aging with HIV-infection

The integration of antiretroviral therapy (i.e., ART) into HIV care has dramatically extended the life expectancy of those living with HIV. However, in comparison to similar HIV-uninfected populations, HIV-infected persons experience an excess of morbidity and mortality with an early onset of aging complications including neurocognitive decline, osteoporosis, impaired physical function, frailty, and falls. Recent consensus guidelines encourage clinicians and researchers to consider functional impairment of HIV-infected adults as a measure to understand the impact of aging across a range of abilities. Despite the importance of assessing function in persons aging with HIV infection, a lack of consistent terminology and standardization of assessment tools has limited the application of functional assessments in clinical or research settings. Herein, we distinguish between different approaches used to assess function, describe what is known about function in the aging HIV population, and consider directions for future research.

Relationship of Physical Function and Quality of Life among Persons Aging with HIV Infection

Objective:Physical function impairments are seen among aging, HIV-infected persons on effective antiretroviral therapy (ART). The impact of physical function impairments on health-related quality of life (QoL) during ART is unknown. Design:This was a cross-sectional study including 359 HIV-infected patients, aged 45–65 years, on ART for more than 6 months. Methods:Patients completed the SF-36 QoL questionnaire, 400-m walk, 5-time chair rise, and grip strength. HIV-associated mortality risk was calculated using the Veterans Aging Cohort Study (VACS) Index. Physical function, physical activity (>500 versus ⩽500 kcal/week), and VACS scores were used to estimate QoL in multivariable linear regression. Results:For every 1 m/s increase in gait speed, we saw an estimated 11.8 [95% confidence interval (CI) 8.4, 15.2] point increase in the physical function scale with smaller differences across all subscales. For every 1 rise/s faster chair rise pace, we saw an estimated 16.0 (95% CI 9.1, 22.9) point increase in the physical function scale with smaller differences across all subscales. SF-36 scores were between 2.8 and 5.7 points higher among more physically active compared to less active patients. A 1 kg increase in grip strength was associated with a 0.2 (95% CI 0.01, 0.3) higher mental health score, but there were no differences in other subscales. VACS scores did not improve the model. Conclusions:Faster gait speed and chair rise time, and greater physical activity were associated with greater QoL, independent of HIV-related mortality risk. Targeted exercise programs to increase physical activity and improve speed and power should be evaluated as interventions to improve QoL during ART.

Association of serum dehydroepiandrosterone sulfate and cognition in older adults: sex steroid, inflammatory, and metabolic mechanisms.

OBJECTIVE Dehydroepiandrosterone sulfate (DHEAS) levels and cognitive function decline with age, and a role for DHEAS in supporting cognition has been proposed. Higher DHEAS levels may be associated with better cognitive performance, although potential mechanisms for this relationship are not well established. METHOD We performed a cross-sectional study of the relationship between serum DHEAS and three aspects of cognition--executive function, working memory, and processing speed--in 49 men and 54 women, aged 60-88 years, with low serum DHEAS levels. We examined three potential mechanisms of DHEAS action--sex hormone sufficiency, inflammatory status, and glucose regulation. RESULTS After adjustment for multiple covariates, higher serum DHEAS levels were associated with better working memory (standardized beta coefficient 0.50, p < .05), with a trend toward better executive function (standardized beta coefficient 0.37, p < .10) in men only. There was a nonsignificant trend toward a negative association between levels of tumor necrosis factor α (TNFα) and working memory in the combined population (standardized beta coefficient -0.22, p < .10). None of the glucoregulatory measures was associated with cognitive function. CONCLUSIONS The relationship between DHEAS and cognition is complex and differs by sex and cognitive domain. This study supports the need for further investigations of the sex-specific effects of DHEAS on cognition and its underlying mechanisms of action.

The Impact of Marijuana Use on the Successful Aging of HIV-Infected Adults.

Objective: To determine the impact of self-reported marijuana use on the components of successful aging of HIV-infected persons. Methods: Cross-sectional study of 45- to 65-year-old HIV-infected subjects on antiretroviral therapy >6 months with undetectable HIV-1 viral load. Successful aging was defined as absence of disease, adequate physical function, high quality of life (QOL), and social engagement. Clinical characteristics, physical function assessments, and QOL from short form 36 were compared between groups defined by self-reported recent marijuana use (RMU), adjusted for tobacco use, CD4+ T-cell count, and time since HIV diagnosis, using logistic or linear regression for binary or continuous measures. Results: 93 of 359 total subjects (26%) reported RMU. Demographically, patients reporting RMU had been diagnosed with HIV less recently [14 (13–16) vs 11 (10–12) years], reported smoking (48% vs 25%) and lower income (92% vs 80%) with greater prevalence than non-RMU patients; other demographics and clinical characteristics (age, CD4+ T-cell count) were similar. Gender, race/ethnicity, physical outcomes, physical function, and disease burden were not significantly different. Patients reporting RMU demonstrated lower mental QOL and increased odds of low social engagement and un- or under-employment compared with nonusers. Conclusions: The negative association between RMU and mental or social QOL should be considered when assessing the success with which HIV patients reporting RMU are aging.

Turning disability into ability: barriers and facilitators to initiating and maintaining exercise among older men living with HIV

ABSTRACT Physical activity reduces the risk for comorbidities, but little is known about barriers to exercise among older adults living with HIV. Three focus groups were conducted among 19 adults living with HIV, aged ≥ 50 years, who were enrolled in or recently completed a supervised exercise intervention. Sessions were recorded, transcribed, and coded first using inductive methods. All participants were male, and the majority were white, non-Hispanic; 53% were receiving disability benefits. All had suppressed HIV infection on antiretroviral therapy, with almost 20 years since HIV diagnosis. Participants noted a lack of self-efficacy, motivation, and physical limitations that contributed to a sense of “disability” as barriers to exercise prior to the intervention. Through social support and improvements in self-efficacy, participants were motivated to start and continue exercising. Perceived sense of disability may impede (or interfere with) exercise initiation and maintenance; self-efficacy and social support may facilitate exercise maintenance in older adults living with HIV.