AIDS Cohort Study Research Articles

Muscle Quality and Physical Function in Men With and Without HIV.

People with HIV (PWH) experience faster physical decline than those without HIV (PWoH), despite antiretroviral therapy. We compared skeletal muscle density and area and their relationship with physical function among PWH and PWoH. Quantitative computed tomography scans were performed at the L4-L5 spinal region and the thigh to evaluate muscle groups in Multicenter AIDS Cohort Study participants at baseline. Using exploratory factor analysis, we summarized aggregated muscle measures based on factor loadings. Longitudinal associations between muscle area and density with gait speed and grip strength were examined using multivariable linear regression models with generalized estimating equations, adjusting for demographics, HIV serostatus, and other health metrics. We included 798 men (61% of PWH). The median age was 54 years (interquartile range: 49-59), 61% were White, 32% Black, and 10% Hispanic. Among them, 22% had a body mass index over 30kg/m2, and 14% had diabetes. Two factors emerged from the factor analysis explaining 55.9% of variance. Factor 1 (explained 32.5% of variance) encompassed all density measures. Factor 2 (explained 23.4% of variance) encompassed all area measures. Associations between muscle density and gait speed were more pronounced with aggregated measures than with individual ones. Specifically, each unit increase in overall muscle density correlated with a 0.028 m/s increase in gait speed (95% confidence interval [CI]: 0.017, 0.038, p < .01). Grip strength was associated with aggregated measures of both muscle density and area, with overall muscle density associated with a 1.88kg increase in grip strength (95% CI: 1.29, 2.46, p < .01), and overall muscle area with a 1.60kg increase (95% CI: 1.02, 2.19, p < .01). Aggregated muscle density and area measurements were significantly associated with physical function. These correlations underscore the importance of interventions to enhance skeletal muscle to improve healthy aging for PWH and PWoH.

Increased incidence of diabetes in people living with HIV treated with first-line integrase strand transfer inhibitors: A French multicentre retrospective study.

Prevention of cardiovascular disease is a major issue in the current management of people living with HIV. Concern is growing about the metabolic impact of integrase strand transfer inhibitors (INSTIs), which could lead to an increased risk of diabetes, but the data are conflicting. This is an updated version of our previous analysis, with longer follow-up and new molecules. We retrospectively evaluated the incidence of new-onset diabetes in people living with HIV starting combined antiretroviral therapy with an INSTI compared with non-nucleoside reverse transcriptase inhibitors and protease inhibitors. Data were collected from the Dat'AIDS cohort study, a collaboration of 30 HIV treatment centres in France. We used a propensity score-based inverse probability of treatment weighting approach to adjust for baseline characteristics between the two groups (INSTI and non-INSTI). Between 2009 and 2021, a total of 12 150 people living with HIV were included. The incidence of diabetes was higher in the INSTI group than in the non-INSTI group (hazard ratio 1.38; 95% confidence interval 1.07-1.77; p = 0.012). Regardless of the third drug, but to a greater extent for INSTIs, we observed a peak of new-onset diabetes in the year following initiation of combined antiretroviral therapy. The incidence of diabetes was higher in people treated with integrase inhibitors than in those receiving other third agents. This increased risk occurred both during the first year of treatment and in the longer term.

Transgender Women With Suppressed Testosterone Display Lower Burden of Coronary Disease Than Matched Cisgender Men.

Cardiovascular disease (CVD) in transgender women (TW) may be affected by gender-affirming hormone therapy (GAHT) and HIV, but few data compare TW on contemporary GAHT to well-matched controls. We compared CVD burden and biomarker profiles between TW and matched cisgender men (CM). Adult TW on GAHT (n = 29) were recruited for a cross-sectional study (2018-2020). CM (n = 48) from the former Multicenter AIDS Cohort Study were matched 2:1 to TW on HIV serostatus, age ±5 years, race/ethnicity, BMI category and antiretroviral therapy (ART) type. Cardiac parameters were measured by CT and coronary atherosclerosis by coronary CT angiography; sex hormone and biomarker concentrations were measured centrally from stored samples. Overall, median age was 53 years and BMI 29 kg/m2; 69% were non-white. All participants with HIV (71%) had viral suppression on ART. Only 31% of TW had testosterone suppression (<50 ng/dL, TW-S). Traditional CVD risk factors were similar between groups, except that TW-S had higher BMI than TW with non-suppressed testosterone (TW-T). TW-S had no evidence of non-calcified coronary plaque or advanced coronary stenosis, whereas TW-T and CM had similar burden. TW had lower prevalence of any coronary plaque, calcified plaque and mixed plaque than CM, regardless of testosterone concentrations and HIV serostatus. Estradiol but not testosterone concentrations moderately and negatively correlated with the presence of coronary plaque and stenosis. Small sample size limited statistical power. Older TW with suppressed total testosterone on GAHT had no CT evidence of non-calcified coronary plaque or advanced coronary stenosis. Longitudinal studies to understand relationships between GAHT and CVD risk in TW are needed.

Vision Problems As a Contributor to Lower Engagement in Care Among Aging Men Living with HIV

ABSTRACT Purpose To investigate vision impairment as a barrier to engagement in medical care among aging persons living with HIV (PLWH) who experience multimorbidity and complex care needs. Setting Multicenter AIDS Cohort Study (MACS), a prospective observational cohort of aging PLWH men. Methods We examined relationships of self-reported vision difficulty with indicators of care engagement: 1) adherence to HIV antiretroviral therapy (ART; defined as taking ≥95% of medications); 2) self-reported avoidance of medical care; 3) self-reported tendency to ask a doctor questions about care (>2 questions at a medical visit), as well as with quality of life. A modified version of the National Eye Institute Vision Function Questionnaire was administered at three semi-annual visits (from October 2017 to March 2019) to assess difficulty performing vision-dependent tasks. Results We included 1063 PLWH (median age 57 years, 31% Black). Data on care engagement outcomes were analyzed using repeated measures logistic regression with generalized estimating equations adjusted for race, and at visit values for age, education level, depressive symptoms, alcohol use, and smoking status. Compared to no vision difficulty, those reporting moderate to extreme vision difficulty on at least one task had 2.2 times higher odds (95% CI: 1.4, 3.4) of having less than optimal ART adherence, 1.9 times higher odds (95% CI: 1.1, 3.4) of avoiding necessary medical care and median quality of life scores 8 points lower. Conclusion These findings suggest vision impairment decreases medical care engagement including HIV care and quality of life among aging PLWH.

Incident Proteinuria by HIV Serostatus Among Men With Pre--Diabetes Mellitus: The Multicenter AIDS Cohort Study.

Pre-diabetes mellitus (DM) is associated with proteinuria, a risk factor for chronic kidney disease. While people with human immunodeficiency virus (HIV; PWH) have a higher risk of proteinuria than people without HIV (PWOH), it is unknown whether incident proteinuria differs by HIV serostatus among prediabetic persons. The urine protein-to-creatinine ratio was measured at semiannual visits among men in the Multicenter AIDS Cohort Study since April 2006. Men with pre-DM on or after April 2006 and no prevalent proteinuria or use of antidiabetic medications were included. Pre-DM was defined as a fasting glucose level of 100-125 mg/dL confirmed within a year by a repeated fasting glucose or hemoglobin A1c measurement of 5.7%-6.4%. Incident proteinuria was defined as a urine protein-to-creatinine ratio (UPCR) >200 mg/g, confirmed within a year. We used Poisson regression models to determine whether incident proteinuria in participants with pre-DM differed by HIV serostatus and, among PWH, whether HIV-specific factors were related to incident proteinuria. Between 2006 and 2019, among 1276 men with pre-DM, proteinuria developed in 128 of 613 PWH (21%) and 50 of 663 PWOH (8%) over a median 10-year follow-up. After multivariable adjustment, the incidence of proteinuria in PWH with pre-DM was 3.3 times (95% confidence interval, 2.3-4.8 times) greater than in PWOH (P < .01). Among PWH, current CD4 cell count <50/µL (P < .01) and current use of protease inhibitors (P = .03) were associated with incident proteinuria, while lamivudine and integrase inhibitor use were associated with a lower risk. Among men with pre-DM, the risk of incident proteinuria was 3 times higher in PWH. Strategies to preserve renal function are needed in this population.

The Relationship Between Posttraumatic Stress Disorder and Alcohol Misuse and Smoking Among Aging Men Who Have Sex With Men: No Evidence of Exercise or Volunteering Impact.

To determine if the association between posttraumatic stress disorder (PTSD) and substance use (alcohol misuse or smoking tobacco) is mediated/moderated by exercise or volunteering among aging (≥40years) men who have sex with men (MSM), and if this mediation/moderation differs by HIV serostatus. Multicenter AIDS Cohort Study data were used. Three datasets with PTSD measured during different time periods (10/1/2017-3/31/2018, 898 men; 4/1/2018-9/30/2018, 890 men; 10/1/2018-3/31/2019, 895 men) were analyzed. Longitudinal mediation analyses estimated the mediation effect of exercise and volunteering on the outcomes. Nine percent of MSM had evidence of PTSD. There was no statistically significant mediation effect of exercise or volunteering regardless of substance use outcome. The odds of smoking at a future visit among MSM with PTSD were approximately double those of MSM without PTSD. Results did not differ by HIV serostatus. There is a particular need for effective smoking cessation interventions for aging MSM with PTSD.

Classification of Free-Living Body Posture with ECG Patch Accelerometers: Application to the Multicenter AIDS Cohort Study.

As health studies increasingly monitor free-living heart performance via ECG patches with accelerometers, researchers will seek to investigate cardio-electrical responses to physical activity and sedentary behavior, increasing demand for fast, scalable methods to process accelerometer data. We extend a posture classification algorithm for accelerometers in ECG patches when researchers do not have ground-truth labels or other reference measurements (i.e., upright measurement). Men living with and without HIV in the Multicenter AIDS Cohort study wore the Zio XT® for up to two weeks (n = 1,250). Our novel extensions for posture classification include (1) estimation of an upright posture for each individual without a reference upright measurement; (2) correction of the upright estimate for device removal and re-positioning using novel spherical change-point detection; and (3) classification of upright and recumbent periods using a clustering and voting process rather than a simple inclination threshold used in other algorithms. As no posture labels exist in the free-living environment, we perform numerous sensitivity analyses and evaluate the algorithm against labelled data from the Towson Accelerometer Study, where participants wore accelerometers at the waist. On average, 87.1% of participants were recumbent at 4am and 15.5% were recumbent at 1pm. Participants were recumbent 54 minutes longer on weekends compared to weekdays. Performance was good in comparison to labelled data in a separate, controlled setting (accuracy = 96.0%, sensitivity = 97.5%, specificity = 95.9%). Posture may be classified in the free-living environment from accelerometers in ECG patches even without measuring a standard upright position. Furthermore, algorithms that fail to account for individuals who rotate and re-attach the accelerometer may fail in the free-living environment.

Study Protocol Using Cohort Data and Latent Variable Modeling to Guide Sampling Women With Type 2 Diabetes and Depressive Symptoms.

Depression affects one in three women with Type 2 diabetes, and this concurrence significantly increases the risks of diabetes complications, disability, and early mortality. Depression is underrecognized because of wide variation in presentation and the lack of diagnostic biomarkers. Converging evidence suggests inflammation is a shared biological pathway in diabetes and depression. Overlapping epigenetic associations and social determinants of diabetes and depression implicate inflammatory pathways as a common thread. This article describes the protocol and methods for a pilot study aimed to examine associations between depressive symptoms, inflammation, and social determinants of health among women with Type 2 diabetes. This is an observational correlational study that leverages existing longitudinal data from the Women's Interagency HIV Study (WIHS), a multicenter cohort of HIV seropositive (66%) and HIV seronegative (33%) women, to inform purposive sampling of members from latent subgroups emergent from a prior retrospective cohort-wide analysis. Local active cohort participants from the Bronx study site are then selected for the study. The WIHS recently merged with the Multicenter Aids Cohort Study (MACS) to form the MACS/WIHS Combined Cohort Study. Latent subgroups represent distinct symptom trajectories resultant from a growth mixture model analysis of biannually collected depressive symptom data. Participants complete surveys (symptom and social determinants) and provide blood samples to analyze plasma levels and DNA methylation of genes that encode for inflammatory markers (CRP, IL-6, TNF-α). Correlation and regression analysis will be used to estimate the effect sizes between depressive symptoms and inflammatory markers, clinical indices (body mass index, hemoglobin A1C, comorbidities), and social determinants of health. The study began in January 2022, and completed data collection is estimated by early 2023. We hypothesize that depressive symptom severity will associate with higher levels of inflammation, clinical indices (e.g., higher hemoglobin A1C), and exposure to specific social determinants of health (e.g., lower income, nutritional insecurity). Study findings will provide the basis for future studies aimed at improving outcomes for women with Type 2 diabetes by informing the development and testing of precision health strategies to address and prevent depression in populations most at risk.

Semiparametric regression analysis of length-biased and partly interval-censored data with application to an AIDS cohort study.

Length-biased data occur often in many scientific fields, including clinical trials, epidemiology surveys and genome-wide association studies, and many methods have been proposed for their analysis under various situations. In this article, we consider the situation where one faces length-biased and partly interval-censored failure time data under the proportional hazards model, for which it does not seem to exist an established method. For the estimation, we propose an efficient nonparametric maximum likelihood method by incorporating the distribution information of the observed truncation times. For the implementation of the method, a flexible and stable EM algorithm via two-stage data augmentation is developed. By employing the empirical process theory, we establish the asymptotic properties of the resulting estimators. A simulation study conducted to assess the finite-sample performance of the proposed method suggests that it works well and is more efficient than the conditional likelihood approach. An application to an AIDS cohort study is also provided.

Pulmonary and physical function limitations in aging men with and without HIV from the Multicenter AIDS Cohort Study (MACS)

We examined the associations between pulmonary impairments and physical function and whether age, HIV serostatus, or smoking modified these relationships. Using Multicenter AIDS Cohort Study data, we examined associations between pulmonary function (diffusing capacity for carbon monoxide [DLCO], one-second forced expiratory volume [FEV1]) and subsequent physical outcomes (gait speed, grip strength, frailty [non-frail, pre-frail, frail]) using mixed models. Of 1,048 men, 55% were living with HIV, median age was 57(IQR=48,64) and median cumulative pack-years was 1.2(IQR=0,18.1); 33% and 13% had impaired DLCO and FEV1(<80% predicted), respectively. Participants with impaired DLCO had 3.5 kg (95%CI: -4.6, -2.4) weaker grip strength, 0.04 m/sec (95%CI: -0.06, -0.02) slower gait speed and 4.44-fold (95%CI: 1.81, 10.93) greater odds of frailty compared to participants with normal DLCO. Participants with impaired FEV1 had 3.1 kg (95%CI: -4.8, -1.4) weaker grip strength, similar gait speed (-0.001 m/sec [95%CI: -0.04, 0.03]) and 5.72-fold (95%CI: 1.90, 17.19) greater odds of frailty compared to participants with normal FEV1. Age, but not smoking or HIV, significantly modified the DLCO effect on gait speed and grip strength. Pulmonary impairment and decreased physical function were associated. Preserving pulmonary function may help preserve physical function in aging men with and without HIV.

Trans women have worse cardiovascular biomarker profiles than cisgender men independent of hormone use and HIV serostatus.

Feminizing hormonal therapy (FHT) and HIV potentially alter cardiovascular disease (CVD) risk in transgender women (TW). TW were enrolled in Los Angeles, California and Houston, Texas and frequency-matched to Multicenter AIDS Cohort Study cisgender men (CM) on age, race, substance use, and abacavir use. Biomarkers of CVD risk and inflammation were assessed via ELISA. Wilcoxon rank sum and Fisher's exact tests compared TW and CM. Multivariable linear regression assessed factors associated with biomarker concentrations. TW (HIV+ n = 75, HIV- n = 47) and CM (HIV+ n = 40, HIV- n = 40) had mean age 43-45 years; TW/CM were 90%/91% non-Hispanic Black, Hispanic, or Multiracial, 26%/53% obese, and 34%/24% current smokers; 67% of TW were on FHT. Among people with HIV (PWH), TW had higher median extracellular newly-identified receptor for advanced glycation end-products (EN-RAGE), lipoprotein-associated phospholipase A2 (LpPLA2), oxidized low-density lipoprotein (oxLDL), soluble tumor necrosis factor receptor type (sTNFR) I/II, interleukin (IL)-8 and plasminogen activator inhibitor (PAI)-1, but lower soluble CD14, von Willebrand factor (vWF) and endothelin (ET)-1 levels than CM. Findings were similar for participants without HIV (all P < 0.05). In multivariable analysis, TW had higher EN-RAGE, IL-6, IL-8, P selectin, PAI-1, oxLDL and sTNFRI/II concentrations, and lower vWF, independent of HIV serostatus and current FHT use. Both being a TW and a PWH were associated with lower ET-1. Compared to matched cisgender men, trans women have altered profiles of biomarkers associated with systemic inflammation and CVD. Further work is needed to decipher the contributions of FHT to CVD risk in TW with HIV.

Suboptimal HIV suppression is associated with progression of coronary artery stenosis: The Multicenter AIDS Cohort Study (MACS) longitudinal coronary CT angiography study

Background and aimsPeople living with HIV (HIV+) are surviving longer due to effective antiretroviral therapy. Cardiovascular disease is a leading cause of non-AIDS related clinical events. We determined HIV-related factors associated with coronary artery stenosis progression. MethodsWe performed serial coronary CT angiography among HIV+ and HIV-uninfected (HIV-) men in the Multicenter AIDS Cohort Study. The median inter-scan interval was 4.5 years. Stenosis was graded as 0, 1–29, 30-49, 50–69 or ≥70%. Progression was defined as an increase ≥2 categories. Suppressed HIV infection was consistent viral loads <50 copies/mL allowing 1 “blip” <500 copies/mL, otherwise considered viremic. Multivariable Poisson regression analysis assessed adjusted associations between HIV serostatus and viremia with coronary stenosis progression. ResultsThe sample included 310 HIV+ (31% viremic) and 234 HIV- men. The median age was 53 years, 30% Black and 23% current smokers. Viremic men were 2.3 times more likely to develop coronary stenosis progression than HIV- men (adjusted RR 2.30; 95% CI, 1.32–4.00, p = 0.003), with no difference in progression between HIV+ suppressed and HIV- men (RR 1.10; 95% CI, 0.70–1.74, p = 0.67). There was a progressive increase in adjusted relative risk with greater viremia (p = 0.03). Men with >1 viral load >500 copies/ml demonstrated greatest stenosis progression (RR 3.01; 95% CI, 1.53–4.92, p = 0.001 compared with HIV- men). Suppressed HIV+ men with suboptimal antiretroviral adherence had greater stenosis progression (RR 1.91; 95% CI 1.12–3.24, p = 0.02) than HIV + suppressed men with optimal adherence. ConclusionsCoronary artery stenosis progression was associated with suboptimal HIV RNA suppression and antiretroviral therapy adherence. Effective ongoing HIV virologic suppression and antiretroviral therapy adherence may mitigate risk for coronary disease events among people living with HIV.

Methods for home-based self-applied polysomnography: the Multicenter AIDS Cohort Study.

Study ObjectivesAlong with multiple chronic comorbidities, sleep disorders are prevalent in people living with human immunodeficiency virus (HIV) infection. The goal of this study was to establish methods for assessing sleep quality and breathing-related disorders using self-applied home polysomnography in people with and without HIV.MethodsSelf-applied polysomnography was conducted on 960 participants in the Multicenter AIDS Cohort Study (MACS) using the Nox A1 recorder to collect data on the frontal electroencephalogram (EEG), bilateral electrooculograms, and a frontalis electromyogram during sleep. Breathing patterns were characterized using respiratory inductance plethysmography bands and pulse oximetry. Continuous recordings of the electrocardiogram were also obtained. All studies were scored centrally for sleep stages and disordered breathing events.ResultsSuccessful home polysomnography was obtained in 807 of 960 participants on the first attempt and 44 participants on the second. Thus, a successful polysomnogram was obtained in 851 (88.6%) of the participants. Reasons for an unsuccessful study included less than 3 h of data on oximetry (34.6%), EEG (28.4%), respiratory inductance plethysmography (21.0%), or two or more of these combined (16.0%). Of the successful studies (N = 851), signal quality was rated as good, very good, or excellent in 810 (95.2%). No temporal trends in study quality were noted. Independent correlates of an unsuccessful study included black race, current smoking, and cocaine use.ConclusionsHome polysomnography was successfully completed in the MACS demonstrating its feasibility in a community cohort. Given the burden of in-lab polysomnography, the methods described herein provide a cost-effective alternative for collecting sleep data in the home.

Study of Treatment and Reproductive Outcomes Among Reproductive-Age Women With HIV Infection in the Southern United States: Protocol for a Longitudinal Cohort Study.

BackgroundNearly a quarter of the 1.1 million individuals with HIV in the United States are women. Racial and ethnic minority women in the Southern United States are disproportionately impacted. Reproductive-age women with HIV are prone to poor HIV outcomes but remain underrepresented in HIV research. We will answer contemporary questions related to the health outcomes in this population by enrolling a prospective cohort of reproductive-age women with and without HIV in the Southern United States.ObjectiveThe Study of Treatment and Reproductive Outcomes (STAR) will enroll and retain 2000 reproductive-age women with and without HIV. The STAR will leverage the infrastructure of the US-based Multicenter AIDS Cohort Study (MACS)/Women’s Interagency HIV Study (WIHS) Combined Cohort Study, comprising the WIHS (a cohort of women with and at risk for HIV, which began in 1993), and the MACS (a cohort of gay and bisexual men with and at risk for HIV, which began in 1984). Although the advancing age of the participants enrolled in the MACS/WIHS Combined Cohort Study provides an opportunity to address the questions related to HIV and aging, the research questions pertinent to the reproductive years must also be addressed. The STAR will conduct high-priority scientific research in key areas with the overall aim of addressing the unique needs of reproductive-age women with HIV.MethodsThe STAR is a prospective, observational cohort study that will be conducted at 6 sites in the United States—Atlanta, Georgia; Birmingham, Alabama; Jackson, Mississippi; Chapel Hill, North Carolina; Miami, Florida; and Washington, District of Columbia. Visits will occur semiannually for 2 years, with additional visits for up to 5 years. At each visit, the participating women will complete a structured interview for collecting key demographic, psychosocial, and clinical variables, and undergo biospecimen collection for laboratory testing and repositing (blood, urine, hair, vaginal, anal, and oral specimens). Pregnant women and infants will undergo additional study assessments. The initial scientific focus of the STAR is to understand the roles of key social determinants of health, depression, reproductive health, and oral health on HIV and pregnancy outcomes across the reproductive life span.ResultsEnrollment in the STAR commenced in February 2021 and is ongoing.ConclusionsThrough in-depth, longitudinal data and biospecimen collection, the newly initiated STAR cohort will create a platform to answer scientific questions regarding reproductive-age women with and without HIV. STAR will be uniquely positioned to enable investigators to conduct high-impact research relevant to this population. Building on the legacy of the MACS and WIHS cohorts, the STAR is designed to foster multidisciplinary collaborations to galvanize scientific discoveries to improve the health of reproductive-age women with HIV and ameliorate the effects of the HIV epidemic in this population in the United States.

Pulmonary and Physical Function Limitations in Aging Men with and without HIV from the Multicenter AIDS Cohort Study

We sought to determine effects of age, HIV serostatus, and smoking on the associations between pulmonary function and physical function impairments using Multicenter AIDS Cohort Study data. Associations between physical function outcomes gait speed (m/sec) and grip strength (kg) with normalized pulmonary function tests (diffusion capacity for carbon monoxide (DLCO, n=1,048) and forced expiratory volume in one second (FEV1, n=1,029)) were examined. Adjusted mixed-effects models included interaction terms to assess effect modification. 574(55%) were HIV+, with median age 57(IQR=48,64) and mean cumulative smoking pack-years 12.2(SD=19.0). 349(33%) had impaired DLCO (<80% of predicted) and 130(13%) had impaired FEV1 (<80% of predicted). Participants with impaired DLCO had weaker grip strength than those with normal DLCO (estimate= -3.5[95% CI=-4.6,-2.4]kg; p<0.001). Participants with impaired DLCO had slower gait speed than those with normal DLCO (estimate= -0.04[95% CI= -0.06,-0.02]m/sec; p=0.002). Age modified the DLCO effect on gait (p-interaction=0.01) but not grip (p-interaction=0.09). The association between decreased DLCO and slower gait was more pronounced in older participants. Smoking or HIV serostatus did not significantly modify the DLCO effect on gait (all p-interaction≥0.14) or grip (p-interaction=0.74, p-interaction=0.058, respectively). As with DLCO, participants with impaired FEV1 had weaker grip strength (estimate=-3.0[95% CI= -4.7,-1.3]kg; p<0.001) than those with normal FEV1. FEV1 was not associated with gait speed(p=0.98). Age, HIV serostatus or smoking did not modify the associations between FEV1 and gait speed or grip strength (all p-interaction>0.05). Associations between lower DLCO/FEV1 and decreased physical function suggest that interventions to improve pulmonary function may also preserve physical function with aging.

Recovering the underlying trajectory from sparse and irregular longitudinal data

In this article, we consider the problem of recovering the underlying trajectory when the longitudinal data are sparsely and irregularly observed and noise‐contaminated. Such data are popularly analyzed with functional principal component analysis via the principal analysis by conditional estimation (PACE) method. The PACE method may sometimes be numerically unstable because it involves the inverse of the covariance matrix. We propose a sparse orthonormal approximation (SOAP) method as an alternative. It estimates the optimal empirical basis functions in the best approximation framework rather than eigen‐decomposing the covariance function. The SOAP method avoids estimating the mean and covariance function, which is challenging when the assembled time points with observations for all subjects are not sufficiently dense. The method also avoids the inverse of the covariance matrix, hence the computation is more stable. It does not require the functional principal component scores to follow the Gaussian distribution. We show that the SOAP estimate for the optimal empirical basis function is asymptotically consistent. The finite‐sample performance of the SOAP method is investigated in simulation studies in comparison with the PACE method. Our method is demonstrated by recovering the CD4 percentage curves from sparse and irregular data in a multi‐centre AIDS cohort study.

Understanding Patterns of Healthy Aging Among Men Who Have Sex With Men: Protocol for an Observational Cohort Study.

BackgroundWith the graying of sexual and gender minority communities and the growing number of people aged ≥50 years living with HIV, it is increasingly important to understand resilience in the context of the psychosocial aspects of aging and aging well.ObjectiveThis paper aims to describe the methods and sample for the Understanding Patterns of Healthy Aging Among Men Who Have Sex With Men study.MethodsThis observational cohort study was conducted within the Multisite AIDS Cohort Study (MACS) and was designed to explore resiliencies to explain patterns of health and illness among middle-aged and older sexual minority men. To be eligible, a participant had to be an active participant in the MACS, be at least 40 years of age as of April 1, 2016, and report any sex with another man since enrollment in the MACS.ResultsEligible participants (N=1318) completed six biannual surveys between April 2016 and April 2019. The mean age of the sample was 59.6 years (range 40-91 years). The sample was mostly White, educated, gay-identified, and included both HIV-positive (656/1318, 49.77%) and HIV-negative (662/1318, 50.23%) men.ConclusionsUnderstanding resiliencies in aging is a critical springboard for the development of more holistic public health theories and interventions that support healthy aging among older sexual minority men.International Registered Report Identifier (IRRID)RR1-10.2196/25750

Legacy effect on neuropsychological function in HIV-infected men on combination antiretroviral therapy.

To determine whether combination antiretroviral therapy (cART) initiation alters the trajectory of cognitive performance in HIV+ men, and whether cognition prior to cART predicts postcART function. Longitudinal cohort study. Multicenter AIDS Cohort Study. From an initial set of 3701 men with complete neuropsychological data, men with HIV infection were initially matched with men without infection on cognitive status, race, age, and timeline (T0 defined as cART initiation). Propensity score matching was then used to match pairs on depressive symptoms at T0, education, T0 cognitive scores, and recruitment cohort. There were 506 matched pairs of infected and uninfected men in the final analysis. Mixed effect models were constructed to analyze the trajectories of cognitive functions and to test the effect of cART and HIV on cognitive functions over time. Performance in each cognitive domain did not change following the initiation of cART among HIV-infected men with prior impairment and was comparable to the performance of their matched uninfected men. However, among the infected men who were unimpaired prior to cART, motor function declined significantly faster than it did for uninfected controls. Cognitive dysfunction is persistent in HIV-infected men and cART does not alter the trajectory of cognitive decline in men who were impaired prior to effective therapy. This suggests that current cognitive impairment in HIV+ men results from a legacy effect, and from factors other than the HIV itself. Furthermore, motor skills may be uniquely vulnerable to the virus, cART, or age-related co-morbidities.

Short Communication: Plasma Lymphocyte Activation Gene 3 and Subclinical Coronary Artery Disease in the Multicenter AIDS Cohort Study.

Chronic inflammation, including among people with HIV (PWH), elevates immune cell expression of lymphocyte activation gene 3 (LAG3); however, low plasma LAG3 predicts cardiovascular disease (CVD) events in the general population. The associations among LAG3 plasma levels, subclinical atherosclerosis, inflammation, and HIV infection have not been well described. We measured plasma LAG3 in 704 men with and without HIV from the multicenter AIDS cohort study, who underwent coronary computed tomography angiography. HIV serostatus was not independently associated with LAG3 after adjustment for sociodemographic and CVD risk factors. Current smoking status and African American race were associated with lower LAG3, and age and sTNFαRI concentration were associated with greater LAG3. LAG3 was not associated with coronary artery stenosis. Thus, no difference was found in plasma LAG3 concentration by HIV serostatus, and no association between LAG3 and subclinical coronary atherosclerosis in men with and without HIV was observed.

Effect of Statin Therapy on Age-Associated Changes in Physical Function Among Men With and Without HIV in the Multicenter AIDS Cohort Study.

The longer-term risks of statins on physical function among people with HIV are unclear. Longitudinal analysis of Multicenter AIDS Cohort Study men between 40 and 75 years of age with ≥2 measures of gait speed or grip strength. Generalized estimating equations with interaction terms between (1) statin use and age and (2) HIV serostatus, age, and statin use were considered to evaluate associations between statin use and physical function. Models were adjusted for demographics and cardiovascular risk factors. Among 2021 men (1048 with HIV), baseline median age was 52 (interquartile range 46-58) years; 636 were consistent, 398 intermittent, and 987 never statin users. There was a significant interaction between age, statin, and HIV serostatus for gait speed. Among people with HIV, for every 5-year age increase, gait speed (m/s) decline was marginally greater among consistent versus never statin users {-0.008 [95% confidence interval (CI) -0.017 to -0.00007]; P = 0.048}, with more notable differences between intermittent and never users [-0.017 (95% CI -0.027 to -0.008); P < 0.001]. Similar results were observed among men without HIV. Significant differences in grip strength (kg) decline were seen between intermittent and never users [-0.53 (95% CI -0.98 to -0.07); P = 0.024] and differences between consistent and never users [-0.28 (95% CI -0.63 to 0.06); P = 0.11] were not statistically significant. Among men with and without HIV, intermittent statin users had more pronounced declines in physical function compared with consistent and never users. Consistent statin use does not seem to have a major impact on physical function in men with or without HIV.