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This article, published in Aging Cell, explores the topic of healthy aging and the various factors that influence it. The authors emphasize the need for a holistic approach to understanding and promoting healthy aging, considering biological pathways, holistic approaches, and interventions targeting multiple organ systems and mechanistic pathways. The article discusses specific topics such as senescent cells, NAD metabolism, genetic variants in centenarians, the African killifish as a model organism, organ crosstalk, cardiorespiratory fitness, and behavioral interventions. The authors also highlight the challenges and future directions in the field of healthy aging research. [Extracted from the article]

Sustainable exercise strategies are needed for older adults to maintain aerobic capacity and strength. The objective of this pilot in 6 adults ≥ 65 years of age was to determine the feasibility and preliminary efficacy of high-intensity functional circuit training which does not require stationary equipment. Instructor-led small group exercise classes were held 3x/week for 12 weeks using weight-bearing exercises performed in a circuit format at ratings of perceived exertion (RPE) of 6–8/10. All 6 participants completed the pilot and showed significant improvements by the Wilcoxon signed-rank test. The six-minute walk distance increased 10.5%. Timed arm curl and chair stands increased 26.8% and 30.3% (all p ≤ 0.03). These preliminary findings suggest that high-intensity functional circuit exercise is feasible in older adults and increases functional measures of aerobic capacity and strength. Further research is warranted to develop this strategy which has the potential for broad dissemination without the need for a traditional exercise facility. [ABSTRACT FROM AUTHOR]

Background Biomarkers that provide insight into drivers of aging are needed for people with human immunodeficiency virus (PWH). The study objective was to determine if epigenetic age acceleration (EAA) markers are associated with physiologic frailty measured by the Veterans Aging Cohort Study (VACS) Index and predict all-cause mortality for PWH. Methods Epigenome-wide DNA methylation was profiled in VACS total white blood cell samples collected during 2005–2007 from 531 PWH to generate 6 established markers of EAA. The association of each EAA marker was tested with VACS Index 2.0. All-cause mortality was assessed over 10 years. For each EAA marker, the hazard ratio per increased year was determined using Cox regression. To evaluate mortality discrimination, C-statistics were derived. Results Participants were mostly men (98.5%) and non-Hispanic Black (84.4%), with a mean age of 52.4 years (standard deviation [SD], 7.8 years). Mean VACS Index score was 59.3 (SD, 16.4) and 136 deaths occurred over a median follow-up of 8.7 years. Grim age acceleration (AA), PhenoAA, HannumAA, and extrinsic epigenetic AA were associated with the VACS Index and mortality. HorvathAA and intrinsic epigenetic AA were not associated with either outcome. GrimAA had the greatest mortality discrimination among EAA markers and predicted mortality independently of the VACS Index. One-year increase in GrimAA was associated with a 1-point increase in VACS Index and a 10% increased hazard for mortality. Conclusions The observed associations between EAA markers with physiologic frailty and mortality support future research to provide mechanistic insight into the accelerated aging process and inform interventions tailored to PWH for promoting increased healthspan. [ABSTRACT FROM AUTHOR]

Polypharmacy is associated with frailty in the general population, but little is known about polypharmacy among persons living with HIV (PLWH) on antiretroviral (ARV) therapy. We determined the association between polypharmacy and an adapted frailty-related phenotype (aFRP) via a cross-sectional study in FY 2009 of 1762 PLWH on ARV with suppressed viral load and 2679 uninfected participants in the Veterans Aging Cohort Study. The primary predictor was number of chronic outpatient non-ARV medications using pharmacy fill/refill data. The outcome was self-report of four aFRP domains: shrinking, exhaustion, slowness, low physical activity. Frailty was defined as reporting 3–4 domains while pre-frailty was 1–2. Frailty was uncommon (2% PLWH, 3% uninfected); a larger proportion demonstrated any aFRP domain (31% PLWH, 41% uninfected). Among PLWH and uninfected, median chronic non-ARV medications was 6 and 16 respectively if having any aFRP domain, and 4 and 10 when without aFRP domains. In adjusted analyses, each additional chronic non-ARV medication conferred an 11% increased odds of having any aFRP domain in PLWH (OR [95% CI] = 1.11 [1.08, 1.14]), and a 4% increase in those uninfected (OR [95% CI] = 1.04 [1.03, 1.04]). The stronger association between polypharmacy and frailty in PLWH warrants further study and potential deprescribing of medications. [ABSTRACT FROM AUTHOR]

Adults with HIV on therapy can live a normal lifespan but exhibit advanced ageing which includes reduced cardiorespiratory fitness. Our objective was to determine the feasibility and effects of high-intensity interval training (HIIT) combined with resistance training (RT) in older adults with HIV. We conducted a cross-over pilot study within a randomized exercise trial in sedentary adults with HIV ≥50 years of age. First, participants were randomized to 4 months of continuous high-intensity aerobic exercise (AEX) and RT 3x/week or standard of care control. Then, the control group completed 4 months of HIIT + RT (3x/week). Among the 32 individuals enrolled, 26 eligible participants were randomized. Most participants were African American (63%) and male (95%) with a mean (SD) age of 61.5 (6.7) years and VO2peak of 24.5 (4.9) ml/kg/min. Attendance and adherence to both exercise training interventions were high. The clinically significant increases in VO2peak (ml/kg/min) after HIIT (3.09 ±1.04, p=0.02) and AEX (2.09 ±0.72, p=0.01) represented improvements of 17.1% and 7.7%, respectively. Both groups had improvements in exercise endurance (time on the treadmill) and strength (all p< 0.01). This pilot study supports HIIT as an efficient means to deliver high-intensity AEX to improve cardiorespiratory fitness toward the goal of attenuating the accelerated ageing process in adults with HIV. [ABSTRACT FROM AUTHOR]

Exercise is critical for health maintenance in late life. The COVID-19 shelter in place and social distancing orders resulted in wide-scale interruptions of exercise therapies, placing older adults at risk for the consequences of decreased mobilization. The purpose of this paper is to describe rapid transition of the Gerofit facility-based group exercise program to telehealth delivery. This Gerofit-to-Home (GTH) program continued with group-based synchronous exercise classes that ranged from 1 to 24 Veterans per class and 1 to 9 classes offered per week in the different locations. Three hundred and eight of 1149 (27%) Veterans active in the Gerofit facility-based programs made the transition to the telehealth delivered classes. Participants' physical performance testing continued remotely as scheduled with comparisons between most recent facility-based and remote testing suggesting that participants retained physical function. Detailed protocols for remote physical performance testing and sample exercise routines are described. Translation to remote delivery of exercise programs for older adults could mitigate negative health effects. [ABSTRACT FROM AUTHOR]

Exercise is critical for health maintenance in late life. The COVID-19 shelter in place and social distancing orders resulted in wide-scale interruptions of exercise therapies, placing older adults at risk for the consequences of decreased mobilization. The purpose of this paper is to describe rapid transition of the Gerofit facility-based group exercise program to telehealth delivery. This Gerofit-to-Home (GTH) program continued with group-based synchronous exercise classes that ranged from 1 to 24 Veterans per class and 1 to 9 classes offered per week in the different locations. Three hundred and eight of 1149 (27%) Veterans active in the Gerofit facility-based programs made the transition to the telehealth delivered classes. Participants' physical performance testing continued remotely as scheduled with comparisons between most recent facility-based and remote testing suggesting that participants retained physical function. Detailed protocols for remote physical performance testing and sample exercise routines are described. Translation to remote delivery of exercise programs for older adults could mitigate negative health effects. [ABSTRACT FROM AUTHOR]

Despite the high prevalence of diastolic dysfunction in adults living with HIV, the impact on cardiorespiratory fitness (CRF) is understudied. The objective of this cross-sectional study was to investigate the relationship between cardiac function and CRF in adults with HIV. Adults receiving antiretroviral therapy with no history of coronary artery disease (CAD) or heart failure were eligible to participate. Cardiac function was assessed by resting Doppler echocardiography. CRF was measured by oxygen utilization at peak exercise (VO2peak). The majority of participants were African American (86%) and male (97%) with a mean [standard deviation (SD)] age of 56.6 (7.1) years and median CD4 lymphocyte count of 492 cells/mL. The mean (SD) VO2peak was 26.1 (5.5) mL/(kg·min). Age, diabetes, hypertension, and hemoglobin were associated with VO2peak. Overall, diastolic dysfunction was present in 38% and was associated with lower VO2peak (p < 0.05). VO2peak was lower among those with impaired myocardial relaxation (e' <8 cm/s) compared with normal relaxation [mean ± SE mL/(kg·min), 25.2 ± 0.6 vs. 27.7 ± 0.9, p < 0.05]. Adjusted for age and clinical factors, each unit increase in left ventricular relaxation (E/A) was associated with an average 4.4 mL/(kg·min) higher VO2peak, representing more than one metabolic equivalent. We conclude that diastolic dysfunction is independently associated with clinically significant low CRF in adults with HIV and no history of CAD or heart failure. These results highlight the importance of recognizing diastolic dysfunction in individuals living with HIV regardless of their cardiovascular disease history. [ABSTRACT FROM AUTHOR]

Introduction: A majority of patients with chronic obstructive pulmonary disease (COPD) die of cardiovascular disease (CVD), yet the mechanisms responsible for this association are not fully understood. It remains unknown if isolated nocturnal oxygen desaturation (iNOD) could be one of the potential pathways by which the 'inflammatory COPD' phenotype leads to CVD. Objectives: We aimed to evaluate if COPD patients who meet the Medicare guidelines for nocturnal oxygen therapy (iNOT+) had higher serum hs‐CRP and IL‐6 than those who did not meet the guidelines for iNOT (iNOT−). Methods: Patients with moderate to severe COPD (ie FEV1 < 80% and FEV1/FVC < 70), who were not on oxygen, underwent nocturnal oximetry on room air. Serum IL‐6 and hs‐CRP were collected the morning after the nocturnal oximetry testing. Results: A total of 28 patients were included in the study, 8 of whom had more than 5 minutes and 5% of their sleep time spent at oxygen saturation less than 88% and constituted the iNOT+ group. Only serum hs‐CRP was significantly higher in iNOT+ than iNOT− (P = 0.050). There was no difference in the rate of COPD exacerbations at one and three months, or five‐year survival between the groups (P > 0.3). Conclusion: COPD patients who have more than 5 minutes and 5% of their sleep time spent at oxygen saturation less than 88% have increased hs‐CRP, which is associated with increased risk of future CVD. [ABSTRACT FROM AUTHOR]

Background: HIV-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. Objective: To determine the safety and efficacy of aerobic exercise in older HIV-infected men in a randomized trial comparing different levels of exercise intensity. Methods: We 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. Results: VO2peak 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. Conclusions: This 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. [ABSTRACT FROM AUTHOR]

Physical function limitations have been associated with poor health outcomes, which have a negative impact on quality of life of older individuals. This study examined the association between depression, viral load, and acculturation with physical function among Latino men living with HIV. A secondary data analysis was performed using a cross-sectional data of 146 Latino immigrant men living with HIV in New York City and Washington, DC. Physical function was measured using the Short-Form Health Survey (SF-12). Uncontrolled HIV infection and depression were associated with worse physical function, thus implying the importance of adequate health care to address these conditions. Preserving physical function should start during middle adulthood, particularly among people living with HIV because of their greater risk of developing age-related challenges such as depression, diabetes, cardiovascular diseases among others. This study informs future interventions to preserve physical function and achieve the goal of successful aging. [ABSTRACT FROM AUTHOR]

Skeletal muscle mitochondrial dysfunction may contribute to low aerobic capacity. We previously reported 40% lower aerobic capacity in HIV-infected men compared to noninfected age-matched men. The objective of this study was to compare skeletal muscle mitochondrial enzyme activities in HIV-infected men on antiretroviral therapy (55 ± 1 years of age, n = 10 African American men) with age-matched controls (55 ± 1 years of age, n = 8 Caucasian men), and determine their relationship with aerobic capacity. Activity assays for mitochondrial function including enzymes involved in fatty acid activation and oxidation, and oxidative phosphorylation, were performed in homogenates prepared from vastus lateralis muscle. Hydrogen peroxide (H2O2), cardiolipin, and oxidized cardiolipin were also measured. β-hydroxy acyl-CoA dehydrogenase ( β- HAD) (38%) and citrate synthase (77%) activities were significantly lower, and H2O2 (1.4-fold) and oxidized cardiolipin (1.8-fold) were significantly higher in HIV-infected men. VO2peak (mL/kg FFM/min) was 33% lower in HIV-infected men and was directly related to β- HAD and citrate synthase activity and inversely related to H2O2 and oxidized cardiolipin. Older HIV-infected men have reduced oxidative enzyme activity and increased oxidative stress compared to age-matched controls. Further research is crucial to determine whether an increase in aerobic capacity by exercise training will be sufficient to restore mitochondrial function in older HIV-infected individuals. [ABSTRACT FROM AUTHOR]

Although it has been shown that human immunodeficiency virus (HIV)-infected adults are at greater risk for aging-associated events, it remains unclear as to whether these events happen at similar, or younger ages, in HIV-infected compared with uninfected adults. The objective of this study was to compare the median age at, and risk of, incident diagnosis of 3 age-associated diseases in HIV-infected and demographically similar uninfected adults. Methods. The study was nested in the clinical prospective Veterans Aging Cohort Study of HIV-infected and demographically matched uninfected veterans, from 1 April 2003 to 31 December 2010. The outcomes were validated diagnoses of myocardial infarction (MI), end-stage renal disease (ESRD), and non-AIDS-defining cancer (NADC). Differences in mean age at, and risk of, diagnosis by HIV status were estimated using multivariate linear regression models and Cox proportional hazards models, respectively. Results. A total of 98 687 (31% HIV-infected and 69% uninfected) adults contributed >450 000 person-years and 689 MI, 1135 ESRD, and 4179 NADC incident diagnoses. Mean age at MI (adjusted mean difference, −0.11; 95% confidence interval [CI], −.59 to .37 years) and NADC (adjusted mean difference, −0.10 [95% CI, −.30 to .10] years) did not differ by HIV status. HIV-infected adults were diagnosed with ESRD at an average age of 5.5 months younger than uninfected adults (adjusted mean difference, −0.46 [95% CI, −.86 to −.07] years). HIV-infected adults had a greater risk of all 3 outcomes compared with uninfected adults after accounting for important confounders. Conclusions. HIV-infected adults had a higher risk of these age-associated events, but they occurred at similar ages than those without HIV. [ABSTRACT FROM AUTHOR]

We found increased acute myocardial infarction risk among hypertensive and prehypertensive HIV-infected veterans compared to normotensive uninfected veterans, independent of confounding comorbidities.Background. Compared to uninfected people, human immunodeficiency virus (HIV)–infected individuals may have an increased risk of acute myocardial infarction (AMI). Currently, HIV-infected people are treated to the same blood pressure (BP) goals (<140/90 or <130/80 mm Hg) as their uninfected counterparts. Whether HIV-infected people with elevated BP have excess AMI risk compared to uninfected people is not known. This study examines whether the association between elevated BP and AMI risk differs by HIV status.Methods. The Veterans Aging Cohort Study Virtual Cohort (VACS VC) consists of HIV-infected and -uninfected veterans matched 1:2 on age, sex, race/ethnicity, and clinical site. For this analysis, we analyzed 81 026 people with available BP data from VACS VC, who were free of cardiovascular disease at baseline. BP was the average of the 3 routine outpatient clinical measurements performed closest to baseline (first clinical visit after April 2003). BP categories used in the analyses were based on criteria of the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Analyses were performed using Cox proportional hazards regression.Results. Over 5.9 years (median), 860 incident AMIs occurred. Low/high prehypertensive and untreated/treated hypertensive HIV-infected individuals had increased AMI risk compared to uninfected, untreated normotensive individuals (hazard ratio [HR], 1.60 [95% confidence interval {CI}, 1.07–2.39]; HR, 1.81 [95% CI, 1.22–2.68]; HR, 2.57 [95% CI, 1.76–3.76]; and HR, 2.76 [95% CI, 1.90–4.02], respectively).Conclusions. HIV, prehypertensive BP, and hypertensive BP were associated with an increased risk of AMI in a cohort of HIV-infected and -uninfected veterans. Future studies should prospectively investigate whether HIV interacts with BP to further increase AMI risk. [ABSTRACT FROM PUBLISHER]

Background: Data regarding the efficacy of directly administered antiretroviral therapy (DAART) are mixed. Opioid treatment programs (OTPs) provide a convenient framework for DAART. In a randomized controlled trial, we compared DAART and self-administered therapy (SAT) among HIV-infected subjects attending five OTPs in Baltimore, MD. Methods: HIV-infected individuals attending OTPs were eligible if they were not taking antiretroviral therapy (ART) or were virologically failing ART at last clinical assessment. In subjects assigned to DAART, we observed one ART dose per weekday at the OTP for up to 12 months. SAT subjects administered ART at home. The primary efficacy comparison was the between-arm difference in the average proportions with HIV RNA <50 copies/mL during the intervention phase (3-, 6-, and 12-month study visits), using a logistic regression model accounting for intra-person correlation due to repeated observations. Adherence was measured with electronic monitors in both arms. Results: We randomized 55 and 52 subjects from five Baltimore OTPs to DAART and SAT, respectively. The average proportions with HIV RNA <50 copies/mL during the intervention phase were 0.51 in DAART and 0.40 in SAT (difference 0.11, 95% CI: −0.020 to 0.24). There were no significant differences between arms in electronically-measured adherence, average CD4 cell increase from baseline, average change in log10 HIV RNA from baseline, opportunistic conditions, hospitalizations, mortality, or the development of new drug resistance mutations. Conclusions: In this randomized trial, we found little evidence that DAART provided clinical benefits compared to SAT among HIV-infected subjects attending OTPs. Trial Registration: ClinicalTrails.gov NCT00279110 NCT00279110&quest;term&hairsp;&equals;&hairsp;NCT00279110&amp;rank&hairsp;&equals;&hairsp;1 [ABSTRACT FROM AUTHOR]

We investigated the association between human immunodeficiency virus (HIV) and prevalence of elevated biomarkers of inflammation, altered coagulation, and monocyte activation in a cohort of HIV-infected and uninfected veterans who had a comparable burden of comorbid conditions.Background. Biomarkers of inflammation, altered coagulation, and monocyte activation are associated with mortality and cardiovascular disease (CVD) in the general population and among human immunodeficiency virus (HIV)–infected people. We compared biomarkers for inflammation, altered coagulation, and monocyte activation between HIV-infected and uninfected people in the Veterans Aging Cohort Study (VACS).Methods. Biomarkers of inflammation (interleukin-6 [IL-6]), altered coagulation (d-dimer), and monocyte activation (soluble CD14 [sCD14]) were measured in blood samples from 1525 HIV-infected and 843 uninfected VACS participants. Logistic regression was used to determine the association between HIV infection and prevalence of elevated (>75th percentile) biomarkers, adjusting for confounding comorbidities.Results. HIV-infected veterans had less prevalent CVD, hypertension, diabetes, obesity, hazardous drinking, and renal disease, but more dyslipidemia, hepatitis C, and current smoking than uninfected veterans. Compared to uninfected veterans, HIV-infected veterans with HIV-1 RNA ≥500 copies/mL or CD4 count <200 cells/µL had a significantly higher prevalence of elevated IL-6 (odds ratio [OR], 1.54; 95% confidence interval [CI],1.14–2.09; OR, 2.25; 95% CI, 1.60–3.16, respectively) and d-dimer (OR, 1.97; 95% CI, 1.44–2.71, OR, 1.68; 95% CI, 1.22–2.32, respectively) after adjusting for comorbidities. HIV-infected veterans with a CD4 cell count <200 cells/µL had significantly higher prevalence of elevated sCD14 compared to uninfected veterans (OR, 2.60; 95% CI, 1.64–4.14). These associations still persisted after restricting the analysis to veterans without known confounding comorbid conditions.Conclusions. These data suggest that ongoing HIV replication and immune depletion significantly contribute to increased prevalence of elevated biomarkers of inflammation, altered coagulation, and monocyte activation. This contribution is independent of and in addition to the substantial contribution from comorbid conditions. [ABSTRACT FROM AUTHOR]

The article focuses on the role of coronary heart disease and alcohol consumption in establishing the connection between human immunodeficiency virus (HIV) and heart failure. A population-based, retrospective cohort study was conducted involving HIV-infected and HIV-uninfected participants who are enrolled in the Veterans Aging Cohort Study Virtual Cohort (VACS-VC) and Large Health Study of Veteran Enrollees (LHS). The study reveals that HIV infection and ongoing viral replication are risk factors for incident heart failure.

Background: HIV-infected drug users are at higher risk of non-adherence and poor treatment outcomes than HIVinfected non-drug users. Prior work from our group and others suggests that directly administered antiretroviral therapy (DAART) delivered in opioid treatment programs (OTPs) may increase rates of viral suppression. Methods/Design: We are conducting a randomized trial comparing DAART to self-administered therapy (SAT) in 5 OTPs in Baltimore, Maryland. Participants and investigators are aware of treatment assignments. The DAART intervention is 12 months. The primary outcome is HIV RNA < 50 copies/mL at 3, 6, and 12 months. To assess persistence of any study arm differences that emerge during the active intervention, we are conducting an 18-month visit (6 months after the intervention concludes). We are collecting electronic adherence data for 2 months in both study arms. Of 457 individuals screened, a total of 107 participants were enrolled, with 56 and 51 randomly assigned to DAART and SAT, respectively. Participants were predominantly African American, approximately half were women, and the median age was 47 years. Active use of cocaine and other drugs was common at baseline. HIV disease stage was advanced in most participants. The median CD4 count at enrollment was 207 cells/mm ³, 66 (62%) had a history of an AIDS-defining opportunistic condition, and 21 (20%) were antiretroviral naïve. Conclusions: This paper describes the rationale, methods, and baseline characteristics of subjects enrolled in a randomized clinical trial comparing DAART to SAT in opioid treatment programs. Trial Registration: ClinicalTrials.gov: NCT00279110 [ABSTRACT FROM AUTHOR]

Background: HIV-infected drug users are at higher risk of non-adherence and poor treatment outcomes than HIVinfected non-drug users. Prior work from our group and others suggests that directly administered antiretroviral therapy (DAART) delivered in opioid treatment programs (OTPs) may increase rates of viral suppression. Methods/Design: We are conducting a randomized trial comparing DAART to self-administered therapy (SAT) in 5 OTPs in Baltimore, Maryland. Participants and investigators are aware of treatment assignments. The DAART intervention is 12 months. The primary outcome is HIV RNA < 50 copies/mL at 3, 6, and 12 months. To assess persistence of any study arm differences that emerge during the active intervention, we are conducting an 18-month visit (6 months after the intervention concludes). We are collecting electronic adherence data for 2 months in both study arms. Of 457 individuals screened, a total of 107 participants were enrolled, with 56 and 51 randomly assigned to DAART and SAT, respectively. Participants were predominantly African American, approximately half were women, and the median age was 47 years. Active use of cocaine and other drugs was common at baseline. HIV disease stage was advanced in most participants. The median CD4 count at enrollment was 207 cells/mm³, 66 (62%) had a history of an AIDS-defining opportunistic condition, and 21 (20%) were antiretroviral naïve. Conclusions: This paper describes the rationale, methods, and baseline characteristics of subjects enrolled in a randomized clinical trial comparing DAART to SAT in opioid treatment programs. Trial Registration: ClinicalTrials.gov: NCT00279110. [ABSTRACT FROM AUTHOR]

HIV clinical care now involves prevention and treatment of age-associated comorbidity. Although physical function is an established correlate to comorbidity in older adults without HIV infection, its role in aging of HIV-infected adults is not well understood. To investigate this question we conducted cross-sectional analyses including linear regression models of physical function in 3227 HIV-infected and 3240 uninfected patients enrolled 2002-2006 in the Veterans Aging Cohort Study-8-site (VACS-8). Baseline self-reported physical function correlated with the Short Form-12 physical subscale (ρ = 0.74, p < 0.001), and predicted survival. Across the age groups decline in physical function per year was greater in HIV-infected patients (βcoef −0.25, p < 0.001) compared to uninfected patients (βcoef −0.08, p = 0.03). This difference, although statistically significant ( p < 0.01), was small. Function in the average 50-year old HIV-infected subject was equivalent to the average 51.5-year-old uninfected subject. History of cardiovascular disease was a significant predictor of poor function, but the effect was similar across groups. Chronic pulmonary disease had a differential effect on function by HIV status (Δβcoef −3.5, p = 0.03). A 50-year-old HIV-infected subject with chronic pulmonary disease had the equivalent level of function as a 68.1-year-old uninfected subject with chronic pulmonary disease. We conclude that age-associated comorbidity affects physical function in HIV-infected patients, and may modify the effect of aging. Longitudinal research with markers of disease severity is needed to investigate loss of physical function with aging, and to develop age-specific HIV care guidelines. [ABSTRACT FROM AUTHOR]

We assessed contractile properties in the knee extensors of 18 men with the human immunodeficiency virus (HIV+) being treated with antiretroviral therapy (ART), and 9 healthy controls matched for age and body mass index. We found significant, divergent differences between groups with regard to force relaxation. Half-times of twitch relaxation were shorter (62.6 ± 5.4 ms vs. 48.9 ± 3.0 ms; p = 0.045) and maximum rates of torque relaxation were slower (0.47% ± 0.04%·s-1 vs. 1.32% ± 0.10%·s-1; p < 0.001) in HIV+ individuals. These preliminary findings suggest potential intramuscular impairments in HIV+ individuals on ART, perhaps because of interactions between calcium handling and mitochondrial dysfunction. Les auteurs de cette étude évaluent les propriétés contractiles des extenseurs du genou de 18 hommes aux prises avec le virus de l'immunodéficience humaine (HIV+) et qui reçoivent le traitement antirétroviral (ART); le groupe de contrôle comprend 9 sujets en bonne santé appariés selon l'âge et l'indice de masse corporelle. On observe des différences significatives entre les groupes en ce qui concerne le relâchement de la tension. Le temps de demi-relaxation de la secousse est plus bref (62,6 ± 5,4 ms comparativement à 48,9 ± 3,0 ms; p = 0,045) et le taux maximal de relâchement de la tension est plus lent (0,47 ± 0,04 %·s-1 comparativement à 1,32 ± 0,10 %·s-1; p < 0,001) chez les sujets aux prises avec le HIV+. Ces observations préliminaires suggèrent de possibles anomalies intramusculaires chez les individus aux prises avec le HIV+ et recevant un ART, et ce, probablement à cause des interactions entre les échanges de calcium et la dysfonction de la mitochondrie. [ABSTRACT FROM AUTHOR]

Background: Health care providers may be concerned that prescribing erectile dysfunction drugs (EDD) will contribute to risky sexual behavior.Objectives: To identify characteristics of men who received EDD prescriptions, determine whether EDD receipt is associated with risky sexual behavior and sexually transmitted diseases (STDs), and determine whether these relationships vary for certain sub-groups.Design: Cross-sectional study.Participants: Two thousand seven hundred and eighty-seven sexually-active, HIV-infected and HIV-uninfected men recruited from eight Veterans Health Affairs outpatient clinics. Data were obtained from participant surveys, electronic medical records, and administrative pharmacy data.Measures: EDD receipt was defined as two or more prescriptions for an EDD, risky sex as having unprotected sex with a partner of serodiscordant or unknown HIV status, and STDs, according to self-report.Results: Overall, 28% of men received EDD in the previous year. Eleven percent of men reported unprotected sex with a serodiscordant/unknown partner in the past year (HIV-infected 15%, HIV-uninfected 6%, P < 0.001). Compared to men who did not receive EDD, men who received EDD were equally likely to report risky sexual behavior (11% vs. 10%, p = 0.9) and STDs (7% vs 7%, p = 0.7). In multivariate analyses, EDD receipt was not significantly associated with risky sexual behavior or STDs in the entire sample or in subgroups of substance users or men who had sex with men.Conclusion: EDD receipt was common but not associated with risky sexual behavior or STDs in this sample of HIV-infected and uninfected men. However, risky sexual behaviors persist in a minority of HIV-infected men, indicating ongoing need for prevention interventions. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To investigate factors related to cardiorespiratory fitness in older human immunodeficiency virus (HIV)-infected patients and to explore the utility of 6-minute walk distance (6-MWD) in measuring fitness. DESIGN: Cross-sectional study in clinic-based cohort. SETTING: Veterans Affairs Medical Center, Baltimore, Maryland. PARTICIPANTS: Forty-three HIV-infected men, median age 57 (range 50–82), without recent acquired immunodeficiency syndrome–related illness and receiving antiretroviral (ARV) therapy. MEASUREMENTS: Peak oxygen utilization (VO2peak) according to treadmill graded exercise testing, 6-MWD, grip strength, quadriceps maximum voluntary isometric contraction, cross-sectional area, muscle quality, and muscle adiposity. RESULTS: There was a moderate correlation between VO2peak (mean ± SD; 18.4 ± 5.6 mL/kg per minute) and 6-MWD (514 ± 91 m) ( r=0.60, P<.001). VO2peak was lower in subjects with hypertension (16%, P<.01) and moderate anemia (hemoglobin 10–13 gm/dL; 15%, P=.09) than in subjects without these conditions. CD4 cell count (median 356 cells/mL, range 20–1,401) and HIV-1 viral load (84% nondetectable) were not related to VO2peak. Among muscle parameters, only grip strength was an independent predictor of VO2peak. Estimation of VO2peak using linear regression, including age, 6-MWD, grip strength, and hypertension as independent variables, explained 61% of the variance in VO2peak. CONCLUSION: Non-AIDS-related comorbidity predicts cardiorespiratory fitness in older HIV-infected men receiving ARV therapy. The 6-MWD is a valuable measure of fitness in this patient population, but a larger study with diverse subjects is needed. [ABSTRACT FROM AUTHOR]

Objective: To examine the association between HIV infection status and the receipt of lipid lowering therapy based on National Cholesterol Education Program/Adult Treatment Panel (NCEP/ATP III) guidelines and to assess whether HIV viral load and hepatitis C (HCV) status alters that association.Participants and Design: A cross-sectional analysis of survey, laboratory, and pharmacy data from 1,577 male participants (59% HIV infected) of the Veterans Aging Cohort Five-Site Study, a prospective observational cohort of U.S. veterans with and without HIV infection.Measurements: Receipt of lipid lowering therapy obtained from the VA pharmacy benefits management system was the main outcome.Results: The prevalence of lipid lowering therapy among HIV-infected and HIV-uninfected veterans was 15.4% vs. 37.9%, respectively, p < 0.01. Among veterans who met NCEP/ATP III criteria for lipid lowering therapy, HIV-infected veterans had a significantly lower prevalence for the receipt of lipid lowering therapy (adjusted odds ratio (OR) = 0.43, 95% confidence interval (C.I.) 0.28-0.67) as compared with HIV-uninfected veterans. Among HIV-infected veterans, log HIV viral load (adjusted OR = 0.57, 95% CI, 0.41-0.81) and HIV-HCV co-infection (adjusted OR = 0.31, 95% CI = 0.13-0.75) were negatively associated with receipt of lipid lowering therapy. Exposure to HAART was not associated with receipt of lipid lowering therapy.Conclusions: Among those who met NCEP/ATP III criteria for lipid lowering therapy, HIV-infected veterans, particularly those with high HIV viral loads and HCV co-infection, were significantly less likely to receive lipid lowering therapy. This may be a modifiable mediator of cardiovascular disease among HIV-infected individuals. [ABSTRACT FROM AUTHOR]

Loss of muscle mass and limitations in activity have been reported in persons infected with human immunodeficiency virus (HIV), even those who are otherwise asymptomatic. The extent to which factors other than muscle atrophy impair muscle performance has not been addressed in depth. The purpose of this study was to determine the extent of neuromuscular activation of the knee extensors and ankle dorsiflexors of 27 men infected with HIV receiving antiretroviral therapy and its relationship to muscle performance. The central activation ratio (CAR) was determined using superimposed electrical stimulation during maximum voluntary contractions. In addition to force and power measurements, muscle cross-sectional area and composition was evaluated using computed tomography. Aerobic capacity was determined from treadmill exercise testing. Eleven of the subjects had an impaired ability to activate the knee extensors (CAR = 0.72 +/- 0.12) that was associated with weakness and decreased specific force. The reduced central activation was not associated with muscle area, body composition, aerobic capacity, CD4 count, or medication regimen. Those individuals with low central activation had higher HIV-1 viral loads and were more likely to have a history of AIDS-defining illness. These results suggest the possibility of a different mechanism contributing to muscle impairment in the current treatment era that is associated with impairment of central motor function rather than atrophy. Further investigation is warranted in a larger, more diverse population before more definitive claims are made. [ABSTRACT FROM AUTHOR]

Comorbidity, aging, and their impact on physical functioning will play an increasingly greater role in HIV medical care as the number of infected adults over 50 years of age grows. The study objective was to investigate the relationship of comorbidity and age with physical functioning in HIV-infected and HIV-negative patients. Eight hundred eighty-nine HIV-infected veterans and 647 HIV-negative veterans from the Veterans Aging Cohort Study conducted between September 2001 and June 2002 were included in the study. Physical functioning was measured by self-reported difficulty with various physical activities. Regression analyses were performed to examine demographic and clinical factors associated with physical functioning. Separate models were used for HIV-infected and HIV negative subjects since these groups differed in demographic makeup. In both patient groups, chronic lung disease, coronary artery disease, hypertension, smoking, and major depression were independently associated with reduced physical functioning in age and race adjusted regression models. Increased age was associated with reduced physical functioning in both HIV-infected and HIV-negative patients. However, when comorbid conditions were entered into the models for both HIV-infected and HIV-negative patients, age coefficients were reduced and were no longer statistically significant. Among the HIV-infected patients, results remained unchanged after controlling for the impact of antiretroviral therapy and HIV disease stage. Our findings demonstrate the important role of general medical comorbidity in physical functioning in both HIV-infected and HIV-negative patients. This suggests the importance of effectively treating comorbid conditions in persons with HIV, in order to reduce the overall impact of disease on physical functioning. [ABSTRACT FROM AUTHOR]

Background: HIV-infected drug users are at higher risk of non-adherence and poor treatment outcomes than HIV-infected non-drug users. Prior work from our group and others suggests that directly administered antiretroviral therapy (DAART) delivered in opioid treatment programs (OTPs) may increase rates of viral suppression.Methods/design: We are conducting a randomized trial comparing DAART to self-administered therapy (SAT) in 5 OTPs in Baltimore, Maryland. Participants and investigators are aware of treatment assignments. The DAART intervention is 12 months. The primary outcome is HIV RNA < 50 copies/mL at 3, 6, and 12 months. To assess persistence of any study arm differences that emerge during the active intervention, we are conducting an 18-month visit (6 months after the intervention concludes). We are collecting electronic adherence data for 2 months in both study arms. Of 457 individuals screened, a total of 107 participants were enrolled, with 56 and 51 randomly assigned to DAART and SAT, respectively. Participants were predominantly African American, approximately half were women, and the median age was 47 years. Active use of cocaine and other drugs was common at baseline. HIV disease stage was advanced in most participants. The median CD4 count at enrollment was 207 cells/mm3, 66 (62%) had a history of an AIDS-defining opportunistic condition, and 21 (20%) were antiretroviral naïve.Conclusions: This paper describes the rationale, methods, and baseline characteristics of subjects enrolled in a randomized clinical trial comparing DAART to SAT in opioid treatment programs.Trial Registration: ClinicalTrials.gov: NCT00279110. [ABSTRACT FROM AUTHOR]