Multicenter AIDS Cohort Study Research Articles

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.

Association between human immunodeficiency virus serostatus and the prevalence of atrial fibrillation.

Atrial fibrillation (AF) leads to increased risk for stroke. Human immunodeficiency virus (HIV) is associated with cardiovascular disease (CVD), although it is unclear if HIV is associated with AF. The purpose of this study was to evaluate the association between HIV serostatus and the prevalence of AF in the Multicenter AIDS Cohort Study.A cross sectional study was conducted among 1674 HIV-infected (HIV+) and uninfected (HIV–) men who completed resting 12-lead electrocardiograms, and/or ambulatory electrocardiogram monitoring. Multivariable logistic regression was used to evaluate the association between AF, defined as the presence of either AF or atrial flutter, and HIV+ serostatus. Associations were adjusted for demographic variables, and then also for CVD risk factors.HIV+ men were younger than HIV– men (median 55.5 vs 61.7 years, P < .001) and were more frequently African-American (30.5% vs 17.8%, P < .001). Most HIV+ men (81%) had undetectable viral load. The age and race adjusted prevalence of AF was 3.0% in HIV+ and 3.3% in HIV– men. There was only 1 case of AF among African-American men. There were no associations between AF and HIV serostatus after adjusting for demographic factors (odds ratio 0.76; 95% CI 0.37 to –1.58; P = .47) or after further adjustment for CVD risk factors (odds ratio 0.84; 95% CI 0.39 to –1.81; P = .66).We found no association between HIV and AF in this cohort in which viral replication among the HIV+ men is generally suppressed. The overall prevalence of AF was low and was rare in African-American men.

Long-term Trajectories of C-Reactive Protein Among Men Living With and Without HIV Infection in the Multicenter AIDS Cohort Study.

C-reactive protein (CRP) is an inflammatory biomarker associated with all-cause mortality and morbidities such as cardiovascular disease. CRP is increased with HIV infection and thought to increase with age, though trajectories of CRP with aging have not been well characterized. We investigated trajectories of CRP in men from the Multicenter AIDS Cohort Study, according to HIV infection and HIV viral load status. CRP measurements from 12 250 serum samples, provided by 2132 men over a span of 30 years, were categorized by HIV status at sample collection: HIV uninfected (HIV-, n = 1717), HIV infected with undetectable RNA (HIV+ suppressed, n = 4075), and detectable HIV RNA (HIV+ detectable, n = 6458). Age-related trajectories of CRP were fit to multivariable linear mixed models; we tested for differences in trajectories by HIV status. CRP increased with age in all sample groups. HIV+ detectable and HIV+ suppressed samples had higher CRP than HIV- samples throughout the observed age range of 20-70 years (p < .05). CRP concentrations at age 45 years were 38% (95% CI: 26%-50%) and 26% (15%-38%) higher in HIV+ detectable and HIV+ suppressed samples, respectively, relative to HIV- samples. HIV+ detectable samples showed more rapid linear increases with age (8% higher/decade, 0.3%-16%) than HIV- samples. We observed higher concentrations of CRP across 5 decades of age in men living with HIV, and steeper increases with age in men with detectable HIV RNA, relative to HIV- men. These results are consistent with a contribution of inflammation to the higher risk of age-related comorbidities with HIV infection.

652 Association Between Poor Sleep and Lymphocyte Subsets In Chronic HIV Infection

Abstract Introduction Low CD4+ T lymphocyte counts and CD4+/CD8+ lymphocyte ratios predict mortality and cardiovascular risk among people living with HIV (PLWH). Whether polysomnographic (PSG) sleep measures impact T lymphocyte subset counts among PLWH is unknown. We sought to evaluate the association between lymphocyte subsets and PSG-derived sleep measures in a cohort with HIV seropositive men. Methods We analyzed data from HIV seropositive men who have sex with men participating in the Multicenter AIDS Cohort Study on antiretroviral therapy for &amp;gt;1 year with undetectable (&amp;lt;500 copies/mL) plasma HIV-1 RNA who underwent a sleep evaluation with home polysomnography. The following seven sleep parameters were examined: total sleep time (TST), sleep efficiency, sleep stage (N1, N2, N3, and REM) duration, and apnea-hypopnea index. Multivariable linear regression models adjusted for age and body mass index were used to assess whether sleep measures were associated with CD4+ T cell count, CD8+ T cell count, or CD4+/CD8+ ratio. Results Participants (n= 286) had a mean age of 55.2 ± 11.3 years, 52.8% had sleep apnea and mean CD4+ count was 728 ± 306 cells/mm3. None of the sleep measures were associated with CD4+ counts but longer TST and REM duration were associated with lower CD8+ counts and higher CD4+/CD8+ ratio. In adjusted analyses, every one hour increase in TST was associated with a 35 ± 18 cells/mm3 lower CD8+ count (p=0.049) and 6.3% elevation in CD4+/CD8+ ratio (p=0.006) while every hour increase in REM was associated with 123 ± 50 cells/mm3 lower CD8+ count (p=0.01) and 20% elevation in CD4+/CD8+ ratio (p=0.003). Conclusion In PLWH, longer total sleep time and REM sleep duration are associated with protective CD4+/CD8+ ratios due to lower CD8+ cell count. Further research is needed to assess if longer sleep duration is associated with decreased inflammatory markers. Support (if any) American Thoracic Society Academic Sleep Pulmonary Integrated Research/Clinical (ASPIRE) Fellowship

Indoleamine 2,3 dioxygenase, age, and immune activation in people living with HIV

Immune activation complicates HIV despite antiretroviral therapy (ART). Indoleamine 2,3 dioxygenase (IDO) catabolizes tryptophan (T) to kynurenine (K), regulating immune activity, and IDO activity increases with age. This study examines...

Self-Reported Cannabis Use and Markers of Inflammation in Men Who Have Sex With Men With and Without HIV.

Background: Chronic inflammation contributes to aging and organ dysfunction in the general population, and is a particularly important determinant of morbidity and mortality among people with HIV (PWH). The effect of cannabis use on chronic inflammation is not well understood among PWH, who use cannabis more frequently than the general population. Materials and Methods: We evaluated participants in the Multicenter AIDS Cohort Study (MACS) beginning in 2004 with available data on cannabis use and inflammatory biomarkers. Associations of current cannabis use with plasma concentrations of inflammatory markers were adjusted for hepatitis C, tobacco smoking, and comorbidities. Markers were analyzed individually and in exploratory factor analysis (EFA). Results: We included 1352 men within the MACS. Twenty-seven percent of HIV-negative men, 41% of HIV viremic men, and 35% of virologically suppressed men reported cannabis use at baseline. Among cannabis users, 20-25% in all groups defined by HIV serostatus were daily users, and the same proportion reported weekly use. The remaining ∼50% of users in all groups reported monthly or less frequent use. Four biomarker groupings were identified by EFA: Factor 1: immune activation markers; Factor 2: proinflammatory cytokines; Factor 3: Th1- and Th2-promoting cytokines; and Factor 4: inflammatory chemokines. In EFA, daily users had 30% higher levels of Factor 2 biomarkers than nonusers (p=0.03); this was the only statistically significant difference by cannabis use status. Among individual markers, concentrations of IL-1β, IL-2, IL-6, and IL-8 (Factor 2); IL-10 (Factor 3); and BAFF (Factor 1) were higher (p<0.05) among daily cannabis users than among nonusers, after adjusting for HIV serostatus and other covariates. Discussion: Associations between daily cannabis use and proinflammatory biomarker levels did not differ by HIV serostatus. Further prospective studies with measured cannabis components are needed to clarify the impact of these compounds on inflammation. Our findings can facilitate for hypothesis generation and selection of biomarkers to include in such studies.

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.

Diagnostic Value of Screening Questions for Vestibular Dysfunction in HIV Disease: A Pilot Study

Introduction: A number of vestibular function tests have been used to evaluate vestibular symptoms among people living with HIV (PLWH). However, these tests are inconsistent due to poor sensitivity and specificity. This study attempts to identify sensitive and specific vestibular symptoms that may be useful in selecting appropriate HIV-positive adults for clinical vestibular function tests. Methods: Participants were enrolled from the Baltimore-Washington, DC, site of the Multicenter AIDS Cohort Study and the Washington, DC, site of the Women’s Interagency HIV Study. A total of 246 participants were evaluated using the Dix-Hallpike (DH) maneuver and the eyes closed, standing on foam (ECF) position in the Romberg test, and completed the Adult Balance and Dizziness Supplemental questionnaire of the 2008 National Health Interview Survey. The sensitivity and specificity were calculated using self-reported vestibular dysfunction from the questionnaire data compared with vestibular dysfunction determined by clinical testing. Results: Sixty participants (24.4%) reported vestibular dysfunction. The prevalence of abnormal tests was 40.8% for DH–any nystagmus, 1.5% for DH–classical nystagmus, 40.3% for DH–nonclassical nystagmus, 38.3% for gaze-evoked nystagmus, and 15.7% for Romberg ECF. Sensitivity of self-reported vestibular symptoms for all vestibular function tests reported ranged from 23.1% to 50.0%. These symptoms were moderately specific and ranged from 73.3% to 77.9%. Conclusions: Despite adequate specificity, the low sensitivity of self-reported symptoms of vestibular dysfunction were not useful to rule out a vestibular disorder in this sample of middle-aged PLWH. Therefore, clinical testing is needed to confirm the diagnosis of a vestibular disorder in the management of HIV disease.

Associations Between HIV Serostatus and Cardiac Structure and Function Evaluated by 2-Dimensional Echocardiography in the Multicenter AIDS Cohort Study.

BackgroundWe aimed to investigate whether there are differences in cardiac structure and systolic and diastolic function evaluated by 2‐dimensional echocardiography among men living with versus without HIV in the era of combination antiretroviral therapy.Methods and ResultsWe performed a cross‐sectional analysis of 1195 men from MACS (Multicenter AIDS Cohort Study) who completed a transthoracic echocardiogram examination between 2017 and 2019. Associations between HIV serostatus and echocardiographic indices were assessed by multivariable regression analyses, adjusting for demographics and cardiovascular risk factors. Among men who are HIV+, associations between HIV disease severity markers and echocardiographic parameters were also investigated. Average age was 57.1±11.9 years; 29% of the participants were Black, and 55% were HIV+. Most men who were HIV+ (77%) were virally suppressed; 92% received combination antiretroviral therapy. Prevalent left ventricular (LV) systolic dysfunction (ejection fraction <50%) was low and HIV serostatus was not associated with left ventricular ejection fraction. Multivariable adjustment models showed that men who were HIV+ versus those who were HIV− had greater LV mass index and larger left atrial diameter and right ventricular (RV) end‐diastolic area; lower RV function; and higher prevalence of diastolic dysfunction. Higher current CD4+ T cell count ≥400 cell/mm3 versus <400 was associated with smaller LV diastolic volume and RV area. Virally suppressed men who were HIV+ versus those who were HIV− had higher indexed LV mass and left atrial areas and greater diastolic dysfunction.ConclusionsHIV seropositivity was independently associated with greater LV mass index, left atrial and RV sizes, lower RV function and diastolic abnormalities, but not left ventricular ejection fraction, which may herald a future predisposition to heart failure with preserved ejection fraction among men living with HIV.

The shifting picture of HIV treatment, comorbidity and substance use among US MSM living with HIV.

People living with HIV (PLWH) have increased risk of chronic disease and poor mental health. We aimed to explore HIV disease indicators, comorbidity, and risk behavior of recent antiretroviral therapy (ART) initiators to inform current needs of PLWH. Men who have sex with men (MSM) in the Multicenter AIDS Cohort Study (MACS) who initiated ART between 2010 and 2018 (recent initiators) were compared with age-, race- and geographic location-matched men who initiated ART during 2000-2009 (early initiators). Measures of HIV disease, behavior, comorbidity and mental health were collected prospectively every 6months using standardized forms. Recent initiators had higher current CD4 (median CD4 451 vs. 307 cells/μL, P<0.0001) and nadir CD4 (451 vs. 300 cells/μL, P<0.0001) than earlier initiators. The proportion achieving viral suppression within a year of starting ART was significantly higher in recent compared with earlier initiators (92% vs. 74%, P<0.0001). Median [interquartile range (IQR)] time from HIV diagnosis to ART initiation was 5.4(1.7-23.1)months in recent initiators. Comorbidity prevalence was high in recent initiators, including obesity (24%), hypertension (25%) and kidney disease (15%). Substance use continues to be common, including cigarette use (40%), daily alcohol use (88%) and marijuana use (46%). Improvements in getting individuals onto ART at an early stage have led to substantially higher CD4 cell counts at initiation. However, the high burden of comorbidity, substance use and poor mental health affecting MSM living with HIV in the US underscore ongoing challenges and our need to adapt and coordinate care.

Expanding the Finnish Diabetes Risk Score for Predicting Diabetes Incidence in People Living with HIV.

This study investigated whether the predictive ability of the Finnish Diabetes Risk Score (FINDRISC) can be improved among people with HIV by adding a marker of insulin resistance. In this longitudinal analysis of the Multicenter AIDS Cohort Study and the Women's Interagency HIV Study, HIV-positive and HIV-negative participants without prevalent diabetes were included. FINDRISC score and the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) were calculated at baseline. Cox proportional hazards models were used to examine associations between baseline risk scores and time to incident diabetes (first self-report of diabetes medication use). Model discrimination (Uno's c-statistic) and calibration (observed vs. cumulative probability of diabetes) were assessed for FINDRISC, HOMA-IR, and combined FINDRISC and HOMA-IR. Overall, 2,527 men (1,299 HIV-positive and 1,228 HIV-negative, median age = 44) and 2,446 women (1,841 HIV-positive and 605 HIV-negative, median age = 41) were included. Over 47,040 person-years of follow-up, diabetes incidence rates per 1,000 person-years were 9.5 in HIV-positive men, 7.1 in HIV-negative men, 14.5 in HIV-positive women, and 15.1 in HIV-negative women. FINDRISC discrimination (HIV-positive men c = 0.64 [0.55, 0.74], HIV-negative men c = 0.74 [0.68, 0.79], HIV-positive women c = 0.68 [0.64, 0.71], and HIV-negative women c = 0.73 [0.66, 0.79]) was significantly better than that of HOMA-IR. FINDRISC was better calibrated than HOMA-IR in each of the four groups. Adding HOMA-IR did not improve FINDRISC discrimination/calibration. Diabetes risk prediction with FINDRISC was suboptimal in men and women with HIV, and its performance was not improved with addition of HOMA-IR. The optimal method for identifying people living with HIV at-risk for diabetes is yet to be identified.

Characteristics of the MACS/WIHS Combined Cohort Study: Opportunities for Research on Aging With HIV in the Longest US Observational Study of HIV.

In 2019, the National Institutes of Health combined the Multicenter AIDS Cohort Study (MACS) and the Women's Interagency HIV Study (WIHS) into the MACS/WIHS Combined Cohort Study (MWCCS). In this paper, participants who made a study visit during October 2018-September 2019 (targeted for MWCCS enrollment) are described by human immunodeficiency virus (HIV) serostatus and compared with people living with HIV (PLWH) in the United States. Participants include 2,115 women and 1,901 men with a median age of 56 years (interquartile range, 48-63); 62% are PLWH. Study sites encompass the South (18%), the Mid-Atlantic/Northeast (45%), the West Coast (22%), and the Midwest (15%). Participant race/ethnicity approximates that of PLWH throughout the United States. Longitudinal data and specimens collected for 35 years (men) and 25 years (women) were combined. Differences in data collection and coding were reviewed, and key risk factor and comorbidity data were harmonized. For example, recent use of alcohol (62%) and tobacco (28%) are common, as are dyslipidemia (64%), hypertension (56%), obesity (42%), mildly or severely impaired daily activities (31%), depressive symptoms (28%), and diabetes (22%). The MWCCS repository includes serum, plasma, peripheral blood mononuclear cells, cell pellets, urine, cervicovaginal lavage samples, oral samples, B-cell lines, stool, and semen specimens. Demographic differences between the MACS and WIHS can confound analyses by sex. The merged MWCCS is both an ongoing observational cohort study and a valuable resource for harmonized longitudinal data and specimens for HIV-related research.

Primary and secondary supportive partnerships among HIV-positive and HIV-negative middle-aged and older gay men.

This study describes the primary and secondary partnerships of aging gay men participating in the Understanding Patterns of Healthy Aging Among Men Who Have Sex with Men substudy of the Multicenter AIDS Cohort Study and examines differences in the prevalence of these relationship structures by HIV status while adjusting for age, education, and race/ethnicity. Relationships were compared within the following structural categories: “only a primary partnership”, “only a secondary partnership”, “both a primary and secondary relationship”, or “neither a primary nor secondary relationship”. There were 1,054 participants (51.9% HIV negative/48.1% HIV positive) included in the study. Participants had a median age of 62.0 years (interquartile range: 56.0–67.0) and most reported being non-Hispanic white (74.6%) and college educated (88.0%). Of the 1,004 participants with available partnership status data, 384 (38.2%) reported no primary or secondary partnerships, 108 (10.8%) reported secondary-only partnership, 385 (38.3%) reported primary-only partnership, and 127 (12.6%) reported both primary and secondary partnerships. Of participants who reported primary partnerships only, the prevalence rates (PRs) were lower among those 62 years and older, HIV positive, black non-Hispanic and Hispanics. Of participants who reported only having a secondary partnership, the PRs were higher among those 62 years and older and HIV positive. Of participants who did not report having either a primary or secondary partnership, the PRs were higher among those 62 years and older, HIV positive, and black non-Hispanic compared with their respective referent groups. There was no significant difference in PRs of having both primary and secondary partnerships by age category, HIV status, race/ethnicity, and education. This study aimed to fill a knowledge gap in the literature regarding both primary and secondary supportive partnerships among aging HIV-positive and HIV-negative gay men.

Outcomes of acute hepatitis B virus (HBV) in HIV infection with and without HBV-active antiretroviral therapy.

Men with acute hepatitis B virus (HBV) infection in the Multicenter AIDS Cohort Study from 1985 to 2013 had serological testing to determine proportions with HBV recovery or chronic hepatitis B (CHB). A similar proportion of men without human immunodeficiency virus (HIV) and men with HIV receiving HBV-active antiretroviral therapy (ART) developed CHB [8.2%, 95% confidence interval (CI) 3.8-15.0% vs. 7.7%, 95% CI 2.00-36.0%]. In contrast, 17.5% (95% CI 8.7-29.9%) of men living with HIV, not on HBV-active ART developed CHB. HBV-active ART protects against developing CHB.

Longitudinal 5-year prediction of cognitive impairment among men with HIV disease.

Although combination antiretroviral therapy reduced the prevalence of HIV-associated dementia, milder syndromes persist. Our goals were to predict cognitive impairment of the Multicenter AIDS Cohort Study (MACS) participants 5 years ahead and from a large pool of factors, select the ones that mostly contributed to our predictions. Longitudinal, natural and treated history of HIV infection among MSM. The MACS is a longitudinal study of the natural and treated history of HIV disease in MSM; the neuropsychological substudy aims to characterize cognitive disorders in men with HIV disease. We modeled on an annual basis the risk of cognitive impairment 5 years in the future. We were able to predict cognitive impairment at individual level with high precision and overperform default methods. We found that while a diagnosis of AIDS is a critical risk factor, HIV infection per se does not necessarily convey additional risk. Other infectious processes, most notably hepatitis B and C, are independently associated with increased risk of impairment. The relative importance of an AIDS diagnosis diminished across calendar time. Our prediction models are a powerful tool to help clinicians address dementia in early stages for MACS paticipants. The strongest predictors of future cognitive impairment included the presence of clinical AIDS and hepatitis B or C infection. The fact that the pattern of predictive power differs by calendar year suggests a clinically critical change to the face of the epidemic.

Social-environmental resiliencies protect against loneliness among HIV-Positive and HIV- negative older men who have sex with men: Results from the Multicenter AIDS Cohort Study (MACS).

Loneliness is associated with negative health outcomes, such as cardiovascular disease, cognitive impairment, dementia, physical functional decline, depression, and increased mortality risk, among HIV- positive and HIV-negative older men who have sex with men (MSM). Given these negative health outcomes, it is imperative to identify factors that minimize loneliness in these vulnerable groups. We sought to examine whether social-environmental resiliencies-defined as an individual's level of support, social bonding, and psychological sense of community among gay men-buffer against symptoms of loneliness. We analyzed longitudinal data from 1,255 older MSM with and without HIV infection, all of whom were enrolled in the Multicenter AIDS Cohort Study (MACS). Using longitudinal latent class analysis (LLCA), we identified three underlying classes (Social Connectors, Non-community Connectors, and Social Isolates) in the social environment of the sample. We assessed the prevalence of loneliness by these latent classes. By lagging social environmental factors over time, we were able to examine the temporal relationships between latent classes and subsequent loneliness. Consistent with our hypothesis, multivariate associations revealed that compared to Social Connectors with high levels of social support and social bonding and a strong perceived sense of community among gay men, Social Isolates (Prevalence Ratio (PR): 1.42; 95% CI: 1.08-1.88; p=0.0120) and Non-community Connectors (PR: 1.34; 95% CI: 1.03-1.75; p=0.0322) were more likely to experience loneliness after adjustment for covariates and baseline loneliness. There were no differences by HIV status. These longitudinal data allowed us to make causal inferences related to the social environmental resiliencies lowering the odds of loneliness among HIV-positive and HIV-negative older MSM. Developing individual- and community-level tailored interventions for these populations by leveraging social environmental resiliencies is key to reducing loneliness and promoting health.

Staying or moving: Results of a latent transition analysis examining intra-individual stability of recreational substance use among MSM in the Multicenter AIDS Cohort Study from 2004 to 2016

BackgroundStudies have examined patterns of substance use among Men who have Sex with Men (MSM), but few have examined factors predicting transitioning from one substance use pattern to another. We investigated transitioning from one substance use pattern to another over a 12-year period (2004–2016) among the Multicenter AIDS Cohort Study participants. MethodAlcohol, marijuana, heroin, cocaine, poppers, uppers (e.g., methamphetamines) and erectile dysfunction(ED) medications use in the last 6 months from 3568 US MSM was dichotomized (no/yes) to classify participants into substance use classes at each follow up visit. We fit latent transition models to calculate transition probabilities of moving from one substance use class to another over a 3, 4 and 6-year time period. Then fit regression models to identify factors associated with the probability of each participant staying in or moving from the same substance use class. ResultsOverall, cocaine and ED medication use declined but marijuana and heroin use increased over 2004−2016. We observed most participants (84.6 %–100 %) stayed in the same class. Increased age was associated with transition from the Minimal-use class to the Alcohol-only class (aOR = 1.06,95 %CI:1.01−1.13;p < 0.01) and non-White MSM reported lower odds of moving from the Alcohol-only class to the Alcohol-Popper class (aOR = 0.50,95 %CI:0.30−0.82;p <0.01). There were no difference in the transition probabilities by HIV-status. ConclusionDespite decline in substance use in general, participants are highly stable in their choice of substances. However, treating MSM as a homogeneous group can lead to an under-appreciation of the diversity of prevention needs and treatment of substance using MSM.

Plasma Lipidomic Profiles and Risk of Diabetes: 2 Prospective Cohorts of HIV-Infected and HIV-Uninfected Individuals.

Antiretroviral therapy (ART) use is associated with disrupted lipid and glucose metabolism in people with HIV infection. We aimed to identify plasma lipid species associated with risk of diabetes in the context of HIV infection. We profiled 211 plasma lipid species in 491 HIV-infected and 203 HIV-uninfected participants aged 35 to 55 years from the Women's Interagency HIV Study and the Multicenter AIDS Cohort Study. Cox proportional hazards model was used to examine associations between baseline lipid species and incident diabetes (166 diabetes cases were identified during a median follow-up of 12.6 years). We identified 11 lipid species, representing independent signals for 8 lipid classes/subclasses, associated with risk of diabetes (P < 0.05 after FDR correction). After adjustment for multiple covariates, cholesteryl ester (CE) (22:4), lysophosphatidylcholine (LPC) (18:2), phosphatidylcholine (PC) (36:4), phosphatidylcholine plasmalogen (34:3), and phosphatidylethanolamine (PE) (38:2) were associated with decreased risk of diabetes (HRs = 0.70 to 0.82 per SD increment), while diacylglycerol (32:0), LPC (14:0), PC (38:3), PE (36:1), and triacylglycerol (50:1) were associated with increased risk of diabetes (HRs = 1.26 to 1.56 per SD increment). HIV serostatus did not modify any lipid-diabetes associations; however, most of these lipid species were positively associated with HIV and/or ART use, including 3 diabetes-decreased ( CE [22:4], LPC [18:2], PE [38:2]) and all 5 diabetes-increased lipid species. This study identified multiple plasma lipid species associated with incident diabetes. Regardless of the directions of their associations with diabetes, most diabetes-associated lipid species were elevated in ART-treated people with HIV infection. This suggests a complex role of lipids in the link between ART and diabetes in HIV infection.

Does Social Support Predict Depressive Symptoms? A Longitudinal Study of Midlife and Older Men Who Have Sex with Men from the Multicenter AIDS Cohort Study.

The present study was designed to identify social support classes across time among midlife (40-64 years) and older (65+ years) gay, bisexual, and other men who have sex with men (MSM), and whether social support protects against depressive symptoms in this population. This study applied longitudinal latent class analysis across five visits on 1,329 individuals age 40 or older at baseline using data from the Multicenter AIDS Cohort Study (MACS) Healthy Aging substudy collected from April 2016 to October 2018. We identified four classes of social support across time: Partner-centered, that is, high levels of support from one's primary partner(s) and moderate support from friends and family; Friend-centered, that is, high levels of support from friends and chosen family; Low, that is, low levels of support from all sources; and Robust, that is, high levels of support from all sources. We found differences in class membership by age, race/ethnicity, employment status, sexual identity, education, relationship status, and HIV status. Finally, compared to MSM in the low support class, men in the other classes had lower odds of depressive symptoms at the final visit. The most common type of social support was partner-centered, while the least common type was robust. These findings suggest that the presence of any social support, regardless of the source, protects against depressive symptoms.

Serological Responses to Toxoplasma gondii and Matrix Antigen 1 Predict the Risk of Subsequent Toxoplasmic Encephalitis in People Living With Human Immunodeficiency Virus (HIV).

Clinically useful predictors for fatal toxoplasmosis are lacking. We investigated the value of serological assays for antibodies to whole Toxoplasma antigens and to peptide antigens of the Toxoplasma cyst matrix antigen 1 (MAG1), for predicting incident toxoplasmic encephalitis (TE) in people living with human immunodeficiency virus (HIV; PLWH). We performed a nested case control study, conducted within the Multicenter AIDS Cohort Study (MACS), using serum samples obtained 2 years prior to diagnosis of TE from 28 cases, and 37 HIV disease-matched Toxoplasma seropositive controls at matched time-points. Sera were tested for Toxoplasma antibodies using a commercial assay and for antibodies to MAG1_4.2 and MAG1_5.2 peptides in enzyme-linked immunosorbent assay (ELISA). Two years prior to clinical diagnosis, 68% of TE cases were MAG1_4.2 seropositive compared with 16% of controls (odds ratio [OR] 25.0, 95% confidence interval [CI] 3.14-199.18). Corresponding results for MAG1_5.2 seropositivity were 36% and 14% (OR 3.6, 95% CI .95-13.42). Higher levels of antibody to MAG1_4.2 (OR 18.5 per doubling of the optical density [OD] value, 95% CI 1.41-242) and to Toxoplasma (OR 2.91 for each OD unit increase, 95% CI 1.48-5.72) were also associated with the risk of TE. When seropositivity was defined as the presence of MAG1 antibody or relatively high levels of Toxoplasma antibody, the sensitivity was 89% and specificity was 68% for subsequent TE. Antibodies to MAG1 showed predictive value on the occurrence of TE in PLWH, and the predictive performance was further improved by adding the levels of Toxoplasma antibody. These measures could be clinically useful for predicting subsequent diseases in multiple at-risk populations.