Older HIV-Infected Adults Research Articles

Polypharmacy Is Associated With Slow Gait Speed and Recurrent Falls in Older People With HIV.

Older people with human immunodeficiency virus (HIV, PWH) are prone to using multiple medications due to higher rates of medical comorbidities and the use of antiretroviral therapy (ART). We assessed the prevalence and clinical impact of polypharmacy among PWH. We leveraged clinical data from the AIDS Clinical Trials Group A5322 study "Long-Term Follow-up of Older HIV-infected Adults: Addressing Issues of Aging, HIV Infection and Inflammation" (HAILO). We included PWH aged ≥40 years with plasma HIV RNA levels <200 copies/µL. We assessed the relationship between polypharmacy (defined as the use of 5 or more prescription medications, excluding ART) and hyperpolypharmacy (defined as the use of 10 or more prescription medications, excluding ART) with slow gait speed (less than 1 meter/second) and falls, including recurrent falls. Excluding ART, 24% of study participants had polypharmacy and 4% had hyperpolypharmacy. Polypharmacy was more common in women (30%) than men (23%). Participants with polypharmacy had a higher risk of slow gait speed (odds ratio [OR] = 1.78; 95% confidence interval [CI] = 1.27-2.50) and increased risk of recurrent falls (OR = 2.12; 95% CI = 1.06-4.23). The risk for recurrent falls was further increased in those with hyperpolypharmacy compared with those without polypharmacy (OR = 3.46; 95% CI = 1.32-9.12). In this large, mixed-sex cohort of PWH aged ≥40 years, polypharmacy was associated with slow gait speed and recurrent falls, even after accounting for medical comorbidities, alcohol use, substance use, and other factors. These results highlight the need for increased focus on identifying and managing polypharmacy and hyperpolypharmacy in PWH.

Polypharmacy and health related quality of life among older adults on antiretroviral therapy in a tertiary hospital in Tanzania: a hospital-based cross-sectional study

BackgroundHuman immunodeficiency virus (HIV) chronicity in the midst of old age multiplies the risk for chronic non communicable diseases. The old are predisposed to drug-drug interactions, overlapping toxicities and impairment of the quality of life (QoL) due to age-related physiological changes. We investigated polypharmacy, QoL and associated factors among older HIV-infected adults at Muhimbili National hospitals in Dar es Salaam Tanzania.MethodsA hospital-based cross sectional study enrolled adults aged 50 years or older who were on antiretroviral therapy (ART) for ≥ 6 months. Participants’ Information including the number and type of medications used in the previous one week were recorded. Polypharmacy was defined as concurrent use of five or more non-HIV medications. A World Health Organization QoL questionnaire for people living with HIV on ART (WHOQoL HIV BREF) was used to assess QoL. A score of ≤ 50 meant poor QoLwhile > 50 meant good QoL. Polypharmacy and QoL are presented as proportions and compared using Chi-square test. Association between various factors and polypharmacy or QoL was assessed using modified Poisson regression. A p-value of < 0.05 was considered significant.ResultsA total of 285 patients were enrolled. The mean (SD) age was 57(± 6.88) years. Females were the majority (62.5%), and 42.5% were married. Polypharmacy was seen in 52 (18.2%) of participants. Presence of co-morbidities was independently associated with polypharmacy (p < 0.001). The mean(SD) score QoL for the study participants was 67.37 ± 11.Poor QoL was seen in 40 (14%) participants.All domains’ mean score were above 50, however social domain had a relatively lowmean scoreof 68 (± 10.10). Having no formal or primary education was independently associated with poor QoL (p = 0.021).ConclusionThe prevalence of polypharmacy was modestly high and was linked to the presence of co-morbidities. No formal and/or primary education was associated with poor QoL, where by social domain of QoL was the most affected.

Clinical profile and predictors of viral suppression in HIV-infected older adults at a University Hospital in Kumasi, Ghana

ABSTRACT Availability of effective antiretroviral therapy (ART) has improved patient survival and older adults (≥50 years old) constitute 10% of the world’s HIV population. However, data on this population are lacking, especially in sub-Saharan Africa. To identify the profile of older adults with HIV infection receiving ART and factors associated with viral suppression. A retrospective cross-sectional study involving HIV patients ≥50 years, registered at a University Hospital in Kumasi, Ghana from January 2010 to July 2020. All study participants had been on ARTs for ≥12 months. Data were analysed using STATA® and multivariate logistic regression was done to determine the association between variables. We recruited 132 study participants with a mean age of 58.1 years (±6.8). Non-communicable diseases (NCD) comprised the commonest comorbidity (67.4%; n = 89) and hypertension was the most prevalent (47.2%). The mean duration of ART was 63.2 months (±32.0) and approximately 84.1% (n = 111) achieved viral suppression (≤50 copies/ml). After adjustment, factors independently associated with viral suppression were widow(ed) (aOR = 0.23; 95% CI = 0.07–0.72) and good ART adherence (aOR = 3.51; 95% CI = 1.03–11.99). Hypertension is prevalent among this cohort of HIV patients. Approximately 84% of elderly patients on ARTs achieve viral suppression, influenced by widowhood and good drug adherence.

Alterations in high-dimensional T-cell profile and gene signature of immune aging in HIV-infected older adults without viremia.

Alterations in the components of the immune system occur with aging. The introduction of combination antiretroviral therapy (ART) has dramatically improved life expectancy in human immunodeficiency virus (HIV) infected individuals by suppressing viral replication and increasing CD4+ T‐cell counts. Immunosenescence‐like changes, including the expansion of memory CD8+ T cells with senescent features, are reported in young HIV‐infected individuals who do not have clinically detectable viremia on ART. However, it is less known whether HIV infection affects the immunosenescent status in older HIV‐infected individuals. Here, we addressed this question in older HIV‐infected, HIV‐uninfected, and frail individuals (all groups age ≥65 years) by examining a set of aging‐associated genes in peripheral blood mononuclear cells (PBMCs) as well as by analyzing subsets of CD4+ and CD8+ T cells in depth using high‐dimensional CyTOF analysis. Older HIV‐infected individuals had increased expression of aging‐associated genes such as CX3CR1 in PBMCs which are related to IL‐7 receptor low effector memory (IL‐7Rαlow EM) CD8+ T cells, a cell population known to expand with age. The subsets of IL‐7Rαlow EM CD8+ T cells expressing senescent, cytotoxic, and inflammatory molecules, including CD57, perforin, and CX3CR1, as well as memory CD4+ T cells expressing CD161 and CXCR3, molecules associated with replication‐competent HIV‐1 harboring cells, were increased in older HIV‐infected individuals. Overall, older HIV‐infected individuals without detectable viremia on ART had augmented levels of age‐associated immune alterations in PBMCs, suggesting that HIV infection has a persistent impact on senescence in older HIV‐infected individuals despite the clinically controlled viremia.

Associations Between Plasma Immunomodulatory and Inflammatory Mediators With VACS Index Scores Among Older HIV-Infected Adults on Antiretroviral Therapy.

The prevalence of age-related comorbidities is increased in people living with HIV, even in those well-controlled on combination antiretroviral therapy (ART). Persistent immune activation and inflammation may play pivotal roles in the pathogenesis; however, the burden of morbidities in the older HIV infected population may be exacerbated and driven by distinct mechanisms. In a cross sectional study of 45 HIV-infected participants 60 years or older, we examined the relationships between 14 immunomodulatory and inflammatory factors and the Veterans Aging Cohort Study (VACS) Index, a metric of multimorbidity and mortality comprised of age, CD4 count, hemoglobin, Fibrosis-4 [FIB-4], and estimated glomerular filtration rate [eGFR], by linear regression analysis. All participants were virally suppressed (<50 HIV RNA copies/mL), on ART, and primarily Caucasian (86.7%), and male (91.1%). Plasma levels of monocyte/macrophage-associated (neopterin, IP-10, sCD163, sCD14, and MCP-1) and glycan-binding immunomodulatory factors (galectin (Gal)-1, Gal-3, and Gal-9) were assessed, as well as inflammatory biomarkers previously linked to the VACS Index (i.e., CRP, cystatin C, TNF-α, TNFRI, IL-6, and D-dimer) for comparison. In regression analysis, higher VACS index scores were associated with higher levels of neopterin, cystatin C, TNFRI, and Gal-9 (all p < 0.05), potentially driven by correlations found with individual VACS components, including age, CD4 count, FIB-4, and eGFR. Gal-9, cystatin C, and TNFRI directly correlated with the extent of multimorbidity. Multiple correlations among markers were observed, suggesting an interplay of overlapping, but distinct, pathways. Collectively, in addition to cystatin C and TNFRI, both galectin-9 and neopterin, independently emerged as novel fluid markers of the VACS Index and burden of comorbidity and may further guide in understanding pathogenic mechanisms of age-related disorders in older HIV-infected individuals on suppressive ART.

HIV Neuropathogenesis in the Presence of a Disrupted Dopamine System.

Antiretroviral therapy (ART) has transformed HIV into a chronic condition, lengthening and improving the lives of individuals living with this virus. Despite successful suppression of HIV replication, people living with HIV (PLWH) are susceptible to a growing number of comorbidities, including neuroHIV that results from infection of the central nervous system (CNS). Alterations in the dopaminergic system have long been associated with HIV infection of the CNS. Studies indicate that changes in dopamine concentrations not only alter neurotransmission, but also significantly impact the function of immune cells, contributing to neuroinflammation and neuronal dysfunction. Monocytes/macrophages, which are a major target for HIV in the CNS, are responsive to dopamine. Therefore, defining more precisely the mechanisms by which dopamine acts on these cells, and the changes in cellular function elicited by this neurotransmitter are necessary to develop therapeutic strategies to treat neuroHIV. This is especially important for vulnerable populations of PLWH with chemically altered dopamine concentrations, such as individuals with substance use disorder (SUD), or aging individuals using dopamine-altering medications. The specific neuropathologic and neurocognitive consequences of increased CNS dopamine remain unclear. This is due to the complex nature of HIV neuropathogenesis, and logistical and technical challenges that contribute to inconsistencies among cohort studies, animal models and in vitro studies, as well as lack of demographic data and access to human CNS samples and cells. This review summarizes current understanding of the impact of dopamine on HIV neuropathogenesis, and proposes new experimental approaches to examine the role of dopamine in CNS HIV infection. Graphical abstract HIV Neuropathogenesis in the Presence of a Disrupted Dopamine System. Both substance abuse disorders and the use of dopaminergic medications for age-related diseases are associated with changes in CNS dopamine concentrations and dopaminergic neurotransmission. These changes can lead to aberrant immune function, particularly in myeloid cells, which contributes to the neuroinflammation, neuropathology and dysfunctional neurotransmission observed in dopamine-rich regions in HIV+ individuals. These changes, which are seen despite the use antiretroviral therapy (ART), in turn lead to further dysregulation of the dopamine system. Thus, in individuals with elevated dopamine, the bi-directional interaction between aberrant dopaminergic neurotransmission and HIV infection creates a feedback loop contributing to HIV associated neurocognitive dysfunction and neuroHIV. However, the distinct contributions and interactions made by HIV infection, inflammatory mediators, ART, drugs of abuse, and age-related therapeutics are poorly understood. Defining more precisely the mechanisms by which these factors influence the development of neurological disease is critical to addressing the continued presence of neuroHIV in vulnerable populations, such as HIV-infected older adults or drug abusers. Due to the complexity of this system, understanding these effects will require a combination of novel experimental modalities in the context of ART. These will include more rigorous epidemiological studies, relevant animal models, and in vitro cellular and molecular mechanistic analysis.

Immunological and Virological Responses in Older HIV-Infected Adults Receiving Antiretroviral Therapy: An Evidence-Based Meta-Analysis

Millions of people living with the HIV have received antiretroviral therapy (ART). Older adults make up a significant portion of these individuals; however, the immunological and virological responses to ART for older patients still need to be clarified. Meta-analysis. In this article, we systematically reviewed research articles published between 2001 and 2018 that reported immunological and virological responses and AIDS-related mortality among HIV- infected adults (including individuals aged 50 years and older) receiving ART, using meta-analysis. ART efficiency was measured using 3 outcomes: (1) immunological response, (2) virological response, and (3) mortality. We identified 4937 citations, and 40 studies were eventually selected to investigate ART efficiency in older HIV-infected patients, comprising more than 888,151 patients initiating ART. We report that older patients showed poor immunological responses, with CD4 counts and the restoration of CD4 counts after ART initiation being significantly lower than seen in younger patients. However, older patients exhibited better viral suppression rates (risk ratio: 1.04; 95% confidence intervals: 1.01 to 1.08) after 36 months following ART initiation. In addition, older adults had a higher risk of AIDS-related death (adjusted hazard ratio: 1.44, 95% confidence interval: 1.30 to 1.60). Older age after ART initiation was associated with a poorer immunological response and a higher risk of mortality, suggesting the need to increase early diagnosis and treatment among older HIV patients.

Older HIV-infected adults: complex patients-comorbidity (I).

Life expectancy in people living with HIV has increased in the past decades, since the introduction of highly active antiretroviral treatment. Increased survival comes along with new challenges for the HIV physician, as these patients will present comorbidities inherent to ageing that can appear more frequently and at younger age than the general population. The older HIV patient poses a unique challenge, as management should take into account different factors, some related to global ageing such as geriatric syndromes, traditional risk factors, social vulnerability, and age-related diseases, and others related to HIV infection like ART toxicity, drug-drug interactions, immune dysregulation and chronic inflammation. All the above can amount to great polypharmacy and multimorbidity that physician have to be aware of. Little is known about the best screening, management and treatment strategies to improve long-term health outcomes in this ageing population. The following article briefly reviews the main comorbidities that can affect the ageing HIV patient.

Older HIV-infected adults. Complex patients (III): Polypharmacy.

Polypharmacy is a well-described problem in the geriatric population. It is a relatively new problem for people living with HIV (PLWH), as this group now has a life expectancy approaching that of the general population. Defining polypharmacy for PLWH is difficult, since the most common traditional definition of at least five medications would encompass a large percentage of PLWH who are on antiretrovirals (ARVs) and medications for other medical comorbidities. Even when excluding ARVs, the prevalence of polypharmacy in PLWH is higher than the general population, and not just in resource-rich countries. Using a more nuanced approach with "appropriate" or "safer" polypharmacy allows for a better framework for discussing how to mitigate the associated risks. Some of the consequences of polypharmacy include adverse effects of medications including the risk of geriatric syndromes, drug-drug interactions, decreased adherence, and over- and undertreatment of medical comorbidities. Interventions to combat polypharmacy include decreasing pill burden-specifically with fixed-dose combination (FDC) tablets- and medication reconciliation/deprescription using established criteria. The goal of these interventions is to decrease drug interactions and improve quality of life and outcomes. Some special populations of interest within the community of PLWH include those with chronic pain, substance abuse, or requiring end of life care. A final look into the future of antiretroviral therapy (ART) shows the promise of possible two-drug regimens, which can help reduce the above risks of polypharmacy.

Human immunodeficiency virus infection and older adults: A retrospective single-site cohort study from Johannesburg, South Africa.

IntroductionHIV-infected adults aged over 50 years in South Africa are increasing. This study explored differences between baseline characteristics and 12-month outcomes of younger and older HIV-infected adults initiated on antiretroviral therapy (ART). Additionally, associations with outcomes within the older group were sought.MethodsWe retrospectively reviewed treatment-naive HIV-infected adult patients at ART initiation. Patients aged 18.0–39.9 years were compared to patients aged over 50 years using log-binomial regression for baseline characteristics and 12-month outcomes. Within the older group, outcome associations were found using multivariate regression.ResultsThe older cohort (n = 1635) compared to the younger cohort (n = 10726) comprised more males (47.2% vs. 35.4%, PR 1.52, p < 0.05), smokers (12.9% vs. 9.7%, PR 1.32, p < 0.05) and overweight patients (26.0% vs. 20.0%, PR 1.32, p < 0.05). Fewer older patients had tuberculosis (10.2% vs. 15.3%, PR 0.67, p < 0.05), other opportunistic infections (16.9% vs. 23.3%, PR 0.70, p < 0.05), World Health Organization stage 3/4 disease (39.9% vs. 43.2%, PR 0.89, p < 0.05), anaemia (22.8% vs. 28.4%, PR 0.77, p < 0.05), liver dysfunction (17.1% vs. 21.3%, PR 0.83, p < 0.05) or low CD4+ count < 100 cells/mm3 (56.3% vs. 59.9%, PR 0.71, p < 0.05).Mortality was higher in the older cohort (11.3% vs. 7.5%, PR 1.48, p < 0.05). Virological suppression was greater in the older cohort (89.5% vs. 86.5%, PR 1.28, p < 0.05) but CD4+ restitution was lower (62.8% vs. 75.0%, PR 0.61, p < 0.05). There was no difference in treatment complications between the groups.Within the older cohort, associations with death were as follows: age > 55 years (PR 1.47, p < 0.05), an AIDS-defining condition (PR 2.28, p < 0.05), raised ALT (PR 1.53, p < 0.05) and CD4+ < 100 cells/mm3 (PR 2.15, p < 0.05). Associations with favourable treatment response at 12 months were unemployment (PR 1.18, p < 0.05) and raised ALT (PR 1.19, p < 0.05). Associations with a treatment complication at 12 months were unemployment (PR 1.12, p < 0.05), smoking (PR 1.20, p < 0.05) and nevirapine use (PR 1.36, p < 0.05) but secondary education was protective (PR 0.87, p < 0.05).ConclusionHIV-infected South African adults aged over 50 years differ in characteristics and outcomes compared to their younger counterparts and justify specialised management within HIV treatment facilities.

575. Older HIV-Infected Adults Are Twice More Likely to Present Late to Care

BackgroundThere are 36.7 million persons living with HIV globally and 1.1 million in the United States with additional ~45,000 new diagnosis annually. One in six newly diagnosed HIV-infected persons is older than 50 years of age. It is estimated that 45% of the US HIV population is over 50 years old and more than 10% are older than 60 years. HIV is more likely to be diagnosed at an advanced stage in older adults. Therefore there is a need to better understand the characteristics, staging of the disease, and response to treatment in older HIV-infected adults, in order to provide an effective treatment and prevention approach.MethodsA retrospective medical record review of all newly diagnosed HIV-infected patients was conducted at a single academic center HIV ambulatory clinic from January 1, 2010 to December 31, 2015. Patients demographics, age group, HIV staging, and response to antiretroviral treatment (ART) measured by HIV viral suppression at 12 weeks (HIV RNA <50 copies), and change in CD4 count were collected. Bivariate analysis was conducted comparing two groups of HIV-infected patients: younger group (age <50 years) and older group (age 50 years and older).ResultsFrom 2010 to 2015, 130 newly diagnosed HIV patients were enrolled in the clinic. Thirty-one (23.8%) were 50 years or older and of those 12 (38.7%) were 60 years and older. Older patients group were more likely to have AIDS defining illness at the time of diagnosis, compared with the younger group [19 (61.3%) vs. 29 (29.3%), respectively]. Of those eight (42%) were older than 60 years. Compared with the younger group, the majority of the HIV-infected patients in the older group who were on ART (61.5%) did not achieve HIV viral suppression at 12 weeks. However, both groups accomplished immune reconstitution with an increase in CD4 cell count in older and younger groups (mean CD4 count = 132 and 200 cell/dl, respectively). More than 80% of patients in both groups were on an integrase inhibitor ART-based regimen.ConclusionHIV-infected patients 50 years and older are more likely to present late to care, and to have a delay in HIV viral suppression compared with younger patient group. These findings are alarming and require emphasize on early HIV diagnosis. More data are required to understand the immune response to cART.Disclosures All authors: No reported disclosures.

Peripheral artery disease in HIV‐infected older adults on antiretroviral treatment in Thailand

HIV infection has become a chronic disease requiring long-term treatment. Premature cardiovascular disease resulting from atherosclerosis in the HIV-infected population has been observed. We assessed the prevalence of peripheral artery disease (PAD), a common consequence of atherosclerosis, in HIV-infected patients aged ≥ 50years receiving antiretroviral treatment (ART). This cross-sectional study was conducted in 12 community hospitals in Chiang Mai, Thailand. Inclusion criteria were as follows: (1) age≥50years, (2) positive HIV status, and (3) currently receiving ART. Age- and sex-matched hospital patients without documented HIV infection were enrolled as a comparison group. Clinical data were extracted from hospital records. Personal information and details of PAD-related symptoms were obtained through face-to-face interviews. The diagnosis of PAD was made using ankle-brachial index (ABI) measurement. Seven hundred and twenty-four participants were enrolled in the study (362 HIV-infected patients and 362 patients in the comparison group). In the HIV-infected group, 43% were male; the mean (± standard deviation) age was 57.8±5.6years. The mean (± standard deviation) times from HIV diagnosis and ART initiation were 10.0±4.3 and 8.6±3.5years, respectively. The prevalence of abnormal ABI (<1.00) was significantly lower in the HIV-infected group than in the comparison group (20 versus 27%, respectively; P=0.03), while that of PAD (ABI ≤0.90) was not significantly different between the two groups (5 and 7%, respectively). In the HIV-infected group, female sex and low body mass index were independently associated with abnormal ABI. The prevalence of PAD when measured by ABI in HIV-infected older adults was relatively low. A follow-up study to determine the incidence of PAD and its persistence with time is warranted.

Cronicidad, envejecimiento y multimorbilidad

Thanks to highly active antiretroviral therapy (HAART), HIV-related mortality has been drastically reduced and HIV infection has become a chronic disease. The HIV-infected population is ageing prematurely. Despite good immunovirological control, HIV causes chronic inflammation and accelerated immunosenes-cence. This clinically manifests as an increased prevalence of age-related comorbidity and frailty occurring earlier than in the general population. The heterogeneity of older HIV-infected adults highlights the rele-vance of identifying those who are at risk of poor health, and frailty may be an effective indicator. The rela-tionship between ageing, HIV infection, antiretroviral treatment, comorbidities and frailty still needs to be clarified. Elderly HIV-infected adults are complex patients who require a specific, global and multidisci-plinary approach.

Comparison of Antiretroviral Therapy Adherence Among HIV-Infected Older Adults with Younger Adults in Africa: Systematic Review and Meta-analysis

As access to antiretroviral treatment in low- and middle-income countries improves, the number of older adults (aged ≥ 50 years) living with HIV is increasing. This study compares the adherence to antiretroviral treatment among older adults to that of younger adults living in Africa. We searched PubMed, Medline, Cochrane CENTRAL, CINAHL, Google Scholar and EMBASE for keywords (HIV, ART, compliance, adherence, age, Africa) on publications from 1st Jan 2000 to 1st March 2016. Eligible studies were pooled for meta-analysis using a random-effects model, with the odds ratio as the primary outcome. Twenty studies were included, among them were five randomised trials and five cohort studies. Overall, we pooled data for 148,819 individuals in two groups (older and younger adults) and found no significant difference in adherence between them [odds ratio (OR) 1.01; 95% CI 0.94–1.09]. Subgroup analyses of studies using medication possession ratio and clinician counts to measure adherence revealed higher proportions of older adults were adherent to medication regimens compared with younger adults (OR 1.06; 95% CI 1.02–1.11). Antiretroviral treatment adherence levels among older and younger adults in Africa are comparable. Further research is required to identify specific barriers to adherence in the aging HIV affected population in Africa which will help in development of interventions to improve their clinical outcomes and quality of life.

A pilot randomized aerobic exercise trial in older HIV-infected men: Insights into strategies for successful aging with HIV.

BackgroundHIV-infected adults have increased risk for age-related diseases and low cardiorespiratory fitness that can be prevented and improved with exercise. Yet, exercise strategies have not been well studied in older adults with HIV and may require substantial adaptation to this special population.ObjectiveTo determine the safety and efficacy of aerobic exercise in older HIV-infected men in a randomized trial comparing different levels of exercise intensity.MethodsWe conducted a pilot exercise trial in 22 HIV-infected men ≥50 years of age receiving antiretroviral therapy who were randomized 1:1 to moderate-intensity aerobic exercise (Mod-AEX) or high-intensity aerobic exercise (High-AEX) that was performed three times weekly for 16 weeks in a supervised setting. Primary outcome was cardiorespiratory fitness (VO2peak) measured by treadmill testing. Secondary outcomes were exercise endurance, six-minute walk distance (6-MWD), body composition measured by Dual-energy X-ray absorptiometry (DXA), and fasting plasma levels of lipids and glucose.ResultsVO2peak increased in the High-AEX group (3.6 ±1.2 mL/kg/min, p = 0.02) but not in the Mod-AEX group (0.4 ±1.4 mL/kg/min, p = 0.7) with a significant between group difference (p<0.01). Exercise endurance increased in both the High-AEX group (27 ±11%, p = 0.02) and the Mod-AEX group (11 ±4%, p = 0.04). The 6-MWD increased in both the High-AEX (62 ±18m, p = 0.01) and the Mod-AEX group (54 ±14m, p = 0.01). Changes in VO2peak and 6-MWD were clinically relevant. There were no serious exercise-related adverse events. Dropouts were similar between group (27% overall) and were related to joint pain.ConclusionsThis pilot exercise trial demonstrates that moderate to high-intensity aerobic exercise in older HIV-infected men increases endurance and ambulatory function. However, increased cardiorespiratory fitness was observed only with high-intensity aerobic exercise despite substantial baseline impairment. Future research is needed to determine exercise strategies in older HIV-infected adults that address advanced aging and comorbidity yet are durable and feasible.

Inflammation Strikes Again: Frailty and HIV.

As a consequence of antiretroviral therapy, the proportion of older HIV-infected adults is increasing, with a concomitant shift in burden of illness to age-related syndromes and disease. Frailty is an age-related syndrome of increased vulnerability to stress, predictive of major adverse clinical outcomes among HIV-infected and uninfected persons alike. Understanding frailty pathogenesis is critical to developing interventions to improve health outcomes in HIV. Here, we review the current evidence for the relationship between inflammation and frailty in HIV, and the potential for novel, inflammation-targeted interventions. Dysregulated inflammation has been consistently associated with frailty in elderly HIV-uninfected persons. Dysregulated inflammation is also central to HIV pathophysiology and several recent studies have demonstrated the important association of inflammation with frailty in HIV. Some evidence suggests that anti-inflammatory therapies may be effective in ameliorating the adverse impact of frailty among aging HIV-infected adults, though further investigation is necessary. Inflammation has been implicated in frailty in HIV infection, and improved understanding of the role that inflammation plays in frailty pathogenesis is key to the development of effective therapies to slow or prevent frailty in the vulnerable HIV-infected population.

Frailty is strongly associated with increased risk of recurrent falls among older HIV-infected adults.

Both frailty and falls occur at earlier-than-expected ages among HIV-infected individuals, but the contribution of frailty-to-fall risk in this population is not well understood. We examined this association among participants enrolled in AIDS Clinical Trials Group (ACTG) A5322. A prospective, multicenter cohort study of HIV-infected men and women aged at least 40 years. Frailty assessment included a 4-m walk, grip strength, and self-reported weight loss, exhaustion, and low physical activity. Multinomial logistic regression assessed the association between baseline frailty, grip, and 4-m walk, and single and recurrent (2+) falls over the next 12 months; logistic regression assessed effect modification by several factors on association between frailty and any (1+) falls. Of 967 individuals, 6% were frail, 39% prefrail, and 55% nonfrail. Eighteen percent had at least one fall, and 7% had recurrent falls. In multivariable models, recurrent falls were more likely among frail (odds ratio 17.3, 95% confidence interval 7.03-42.6) and prefrail (odds ratio 3.80, 95% CI 1.87-7.72) than nonfrail individuals. Significant associations were also seen with recurrent falls and slow walk and weak grip. The association between frailty and any falls was substantially stronger among individuals with peripheral neuropathy. Aging HIV-infected prefrail and frail individuals are at significantly increased risk of falls. Incorporation of frailty assessments or simple evaluations of walk speed or grip strength in clinical care may help identify individuals at greatest risk for falls. Peripheral neuropathy further increases fall risk among frail persons, defining a potential target population for closer fall surveillance, prevention, and treatment.

Diminished physical function in older HIV-infected adults in the Southeastern U.S. despite successful antiretroviral therapy.

BackgroundAs antiretroviral therapy efficacy improves, HIV is gradually being recognized more as a chronic disease within the aging HIV-infected population. While these individuals are surviving into old age, they may, however, be experiencing “accelerated aging” with greater declines in physical function than that observed among comparably matched individuals free of HIV. This decline is not well understood and it remains unclear if physical decline correlates with the degree of immunosuppression based on CD4 lymphocyte nadir.MethodsIn a cross-sectional study of accelerated aging in the older HIV-infected population on antiretroviral therapy (ART), physical performance evaluations were completed on a cohort of 107 HIV-infected subjects, age 50 years or older (with no HIV-1 RNA >200 copies/mL in the prior 12 months), and compared to reference ranges for age- and gender-matched HIV-uninfected persons. Physical performance testing consisted of four validated assessments: the 2.4-meter walk, 30-second chair stand, grip strength and 6-minute walk test.ResultsWhen compared to age- and gender-matched HIV-uninfected reference controls, older HIV-infected persons had diminished physical function. No correlation was found between physical function and degree of immunosuppression as determined by pre-ART CD4 nadir.ConclusionsDespite improved survival, HIV–infected adults on suppressive ART have diminished physical function compared to HIV-uninfected persons. The degree of HIV-associated immunosuppression does not correlate with the observed degree of physical function decline in older HIV-infected persons, suggesting the decline is mediated by other mechanisms.

Attitudes towards exercise among substance using older adults living with HIV and chronic pain

ABSTRACTChronic pain and substance use disorders occur commonly among HIV-infected persons. Recent CDC guidelines recommend non-pharmacologic approaches over opioid medications for the management of chronic pain. This is particularly relevant for persons with substance use disorders. Structured physical activity may be an effective strategy for pain reduction. We developed a combined cognitive-behavioral therapy (CBT) + exercise intervention to reduce pain, pain-related disability and substance use and improve physical function in older HIV-infected adults with chronic pain and substance use. We employed established CBT protocols for the intervention, and sought feedback from potential end users when developing the exercise component of the intervention. A total of 27 HIV-infected adults ≥ 50 years of age participated in four focus group sessions. Transcripts were analyzed using thematic analysis. Participant demographics: mean age 54 years; male 81%; Hispanic 48%, Black 33%; treated for substance abuse in the past 52%. Exercise was seen as a desirable activity, but many participants expressed barriers to exercise including fear of pain exacerbation, low physical fitness, and lack of availability of perceived safe spaces for HIV-infected persons. Most participants were receptive to exercise for pain reduction, particularly modalities that provide added psychological benefits of reducing stress and anxiety. Exercise for pain management among older HIV-infected adults with chronic pain and substance use was found to be highly acceptable. However, interventions need to be tailored to the unique needs of this population to address their fears and concerns.

Interaction Effects between HIV and Aging on Selective Neurocognitive Impairment.

HIV infection and aging are each associated with neurocognitive impairment (NCI). This study examined the combined effects of HIV infection and aging on NCI. We performed a cross-sectional survey among 345 HIV-infected and 345 HIV-uninfected participants aged at least 40years. The International HIV Dementia Scale (IHDS) and Chinese version of Mini-mental State Examination (MMSE) were administered to screen for NCI. HIV-infected individuals had higher prevalence of NCI than uninfected individuals (46.7% vs 15.1% for IHDS using cut-off of ≤10; 17.1% vs 2.6% for MMSE). Significant main effects of HIV and age were observed on IHDS and MMSE composite scores and all domains except for HIV on attention and calculation. Significant interaction effects between HIV and age were observed on motor speed, orientation, registration and recall, and mainly attributed to the inferior performance of HIV-infected patients aged over 60years. Among HIV-infected individuals, in multivariable logistic models, older age, depressive symptoms and history of nevirapine treatment were associated with NCI using both IHDS and MMSE, whereas lower education current smoker and current CD4≥800 cells/μL were associated only with NCI using IHDS, and hypertension was associated only with NCI using MMSE. Findings suggest that HIV and older age may confer interactive effects on cognitive function in several domains with older HIV-infected adults experiencing greater NCI, which requires further longitudinal investigation. Furthermore, HIV early diagnosis and treatment may prevent or reverse NCI, but extra attention should be given to adverse effects including metabolic changes associated with long-term treatment.