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ObjectiveExamine prospective relationships between erectile dysfunction (ED) drugs EDand CD4 and CD8 T-cells, and immune markers among men who have sex with men (MSM).MethodsData from Multicenter AIDS Cohort Study, an observational prospective cohort study, with semi-annual follow-ups conducted in four U.S. centers from 1998 onwards was used. Marginal structural models using g-computation was fitted to estimate the mean differences for the effects of self-reported ED drug use on CD4 and CD8 T-cell outcomes and immune biomarkers.ResultsTotal of 1,391 men with HIV (MWH) and 307 men without HIV (MWOH) was included. Baseline mean CD4 cell count among MWH and MWOH was 499.9 cells/μL and 966.7 cells/μL, respectively. At baseline, 41.8% of MWH were virally suppressed. ED drug users reported a mean of 44.4 months of exposure to ED drugs. ED drug use was associated with increased CD4 cell outcomes among MWH but not MWOH. Mean differences in CD4 cell counts after 1 year of ED drug use was 57.6 cells/μL and increased to 117.7 after 10 years among MWH. CD8 counts were higher in ED drug users among MWH over 10 years than non-users; no consistent differences were found among MWOH. ED drug use appeared to reduce immune marker levels, such as IL-6 and increase markers, such as IL-10. We observed similar effects of ED drug use on biomarker levels among MWOH.ConclusionLong-term use of ED drugs do not adversely affect immune function among MWH or MWOH. Future studies on the relationships between different types of ED drugs and effects on T-cell subtypes are warranted.

We investigated the longitudinal relationship between erectile dysfunction (ED) drug use with behavioral factors, including substance use and sexual activities in men who have sex with men from the Multicenter AIDS Cohort Study during 1998-2016 (n = 1636). We used a bivariate random-intercept model to evaluate ED drug use along with other behavioral factors to assess relationships between the two outcomes over time on a population level and also at the individual level. Average ED drug use among men who have sex with men (MSM) with HIV was positively correlated with average use of marijuana (r = .19), poppers (r = .27), and stimulants (r = .25). In this group, testosterone use (r = .32), multiple partners (r = .41), insertive anal intercourse with condom (r = .40), and insertive anal intercourse without condom (r = .43) all showed moderate correlations over time with average ED use (p

Purpose: The COVID-19 pandemic posed unique challenges to cancer-related care as health systems balanced competing risks of timely delivery of care and minimizing exposure to infection in a high-risk, immunocompromised patient population. This study aimed to better understand how pandemic-related factors affected the patient experience of cancer care during this time. Methods: We conducted fifteen semi-structured interviews with adults from rural counties in Maryland who were diagnosed with and/or actively treated for cancer at the TidalHealth healthcare network between January 2020 and October 2022. Results: Interviews from fifteen participants were analyzed. Two major themes emerged including COVID Impact on Care, and COVID Impact on Mental Health. Subthemes under COVID Impact on Care include Staffing Shortages, Hospital Regulations, Visitation, Importance of Advocacy, and Telehealth Utilization, and subthemes under COVID Impact on Mental Health include Loneliness, Support Networks, and Perceptions of COVID and Personal Protection. Overall, participants described positive care experiences despite notable delays, disruptions to continuity of care, difficult transitions to telemedicine, visitation policies that limited patient support, increased mental health struggles related to social distancing measures, and greater desire for patient advocacy. Conclusion: Our findings reveal significant impacts of the COVID-19 pandemic on experiences of cancer treatment and survivorship in a more vulnerable, rural patient population with lower healthcare access and income level. Our findings suggest areas for targeted interventions to limit disruptions to quality care in future public health emergencies. [ABSTRACT FROM AUTHOR]

The relationship between testosterone and related hormones and cardiovascular and mortality outcomes is debated. The authors of this study obtained individual patient–level data from 9 cohort studies and aggregate data from 11 studies in total. These data enabled them to describe the associations of testosterone, sex hormone–binding globulin (SHBG), luteinizing hormone (LH), dihydrotestosterone (DHT), and estradiol with all-cause mortality, cardiovascular death, and incident cardiovascular events while accounting for other cardiac risk factors. Background: Whether circulating sex hormones modulate mortality and cardiovascular disease (CVD) risk in aging men is controversial. Purpose: To clarify associations of sex hormones with these outcomes. Data Sources: Systematic literature review to July 2019, with bridge searches to March 2024. Study Selection: Prospective cohort studies of community-dwelling men with sex steroids measured using mass spectrometry and at least 5 years of follow-up. Data Extraction: Independent variables were testosterone, sex hormone–binding globulin (SHBG), luteinizing hormone (LH), dihydrotestosterone (DHT), and estradiol concentrations. Primary outcomes were all-cause mortality, CVD death, and incident CVD events. Covariates included age, body mass index, marital status, alcohol consumption, smoking, physical activity, hypertension, diabetes, creatinine concentration, ratio of total to high-density lipoprotein cholesterol, and lipid medication use. Data Synthesis: Nine studies provided individual participant data (IPD) (255 830 participant-years). Eleven studies provided summary estimates (n = 24 109). Two-stage random-effects IPD meta-analyses found that men with baseline testosterone concentrations below 7.4 nmol/L (<213 ng/dL), LH concentrations above 10 IU/L, or estradiol concentrations below 5.1 pmol/L had higher all-cause mortality, and those with testosterone concentrations below 5.3 nmol/L (<153 ng/dL) had higher CVD mortality risk. Lower SHBG concentration was associated with lower all-cause mortality (median for quintile 1 [Q1] vs. Q5, 20.6 vs. 68.3 nmol/L; adjusted hazard ratio [HR], 0.85 [95% CI, 0.77 to 0.95]) and lower CVD mortality (adjusted HR, 0.81 [CI, 0.65 to 1.00]). Men with lower baseline DHT concentrations had higher risk for all-cause mortality (median for Q1 vs. Q5, 0.69 vs. 2.45 nmol/L; adjusted HR, 1.19 [CI, 1.08 to 1.30]) and CVD mortality (adjusted HR, 1.29 [CI, 1.03 to 1.61]), and risk also increased with DHT concentrations above 2.45 nmol/L. Men with DHT concentrations below 0.59 nmol/L had increased risk for incident CVD events. Limitations: Observational study design, heterogeneity among studies, and imputation of missing data. Conclusion: Men with low testosterone, high LH, or very low estradiol concentrations had increased all-cause mortality. SHBG concentration was positively associated and DHT concentration was nonlinearly associated with all-cause and CVD mortality. Primary Funding Source: Medical Research Future Fund, Government of Western Australia, and Lawley Pharmaceuticals. (PROSPERO: CRD42019139668) [ABSTRACT FROM AUTHOR]

The relation between insulin resistance (IR) and coronary artery disease in patients with human immunodeficiency virus (HIV) infection remains incompletely defined. Fasting serum insulin and glucose measurements from 448 HIV-infected and 306 uninfected men enrolled in the Multicenter AIDS Cohort Study were collected at semiannual visits from 2003 to 2013 and used to compute the homeostatic model assessment of IR (HOMA-IR). Coronary computed tomographic angiography (CTA) was performed at the end of the study period to characterize coronary pathology. Associations between HOMA-IR (categorized into tertiles and assessed near the time of the CTA and over the 10-year study period) and the prevalence of coronary plaque or stenosis ≥50% were assessed with multivariate logistic regression. HOMA-IR was higher in HIV-infected men than HIV-uninfected men when measured near the time of CTA (3.2 vs 2.7, p = 0.002) and when averaged over the study period (3.4 vs 3.0, p

BackgroundAging in males is associated with lower testosterone levels and a decrease in diurnal variation of testosterone secretion. Cross-sectional studies have shown lower than expected testosterone levels among HIV-infected men, but whether age-related changes in serum testosterone differ by HIV serostatus are not known.MethodsHIV-infected men from the Multicenter AIDS Cohort Study (MACS), age ≥ 45 years at highly active antiretroviral therapy initiation, who had ≥ 2 samples from the subsequent 10 years, were matched to HIV-uninfected men by age, race, MACS site, and calendar time of samples. Linear mixed-effects regression models were used to determine whether free testosterone (FT) and its rate of change differed by HIV serostatus.ResultsOne hundred eighty-two HIV-infected and 267 HIV-uninfected men were included, median age: 48.8 years (interquartile range: 45.8-53.4), median numbers of FT measurements per participant 4 (interquartile range: 3-5), 65% were drawn in the adjusted morning (AM). Mean-adjusted FT levels were lower among HIV-infected than HIV-uninfected men in AM samples {-6.1 ng/dL [95% confidence interval (CI): -9.8 to -2.4], P = 0.001}, but not in afternoon samples [-1.7 ng/dL (-6.0 to 2.6), P = 0.441]. The rate of FT decline with age did not differ by HIV serostatus: 9.2 ng/dL (95% CI: -13.4 to -5.0) per 10 years for HIV-infected vs. 7.9 ng/dL (95% CI: -10.2 to -5.5) for HIV-uninfected men, P = 0.578.ConclusionsFT decreased similarly with increasing age regardless of HIV serostatus. The lower AM, but not adjusted afternoon, FT levels among HIV-infected men compared with HIV-uninfected men suggest a loss of diurnal variation in FT levels among HIV-infected men.

ContextAbnormalities in the osteoprotegerin (OPG)/receptor activator of nuclear factor-κB ligand (RANKL) axis have been observed in HIV-infected persons and have been implicated in cardiovascular disease (CVD) pathogenesis in the general population.ObjectiveTo determine associations of serum OPG and RANKL concentrations with HIV infection and subclinical atherosclerosis.DesignCross-sectional study nested within the Multicenter AIDS Cohort Study.SettingFour US academic medical centers.ParticipantsThere were 578 HIV-infected and 344 HIV-uninfected men.Main outcome measuresCoronary artery calcium (CAC) was measured by noncontrast cardiac computed tomography, and coronary stenosis and plaque characteristics (composition, presence, and extent) were measured by coronary computed tomography angiography. All statistical models were adjusted for traditional CVD risk factors.ResultsOPG concentrations were higher, and RANKL concentrations were lower among HIV-infected men compared with HIV-uninfected men (P < 0.0001 each). Among HIV-infected men, higher OPG concentrations were associated with the presence of CAC, mixed plaque, and coronary stenosis >50%, but not with plaque extent. In contrast, among HIV-uninfected men, higher OPG concentrations were associated with the extent of both CAC and calcified plaque, but not with their presence. RANKL concentrations were not associated with plaque presence or the extent among HIV-infected men, but among HIV-uninfected men, lower RANKL concentrations were associated with greater extent of CAC and total plaque.ConclusionsOPG and RANKL are dysregulated in HIV-infected men, and their relationship to the presence and extent of subclinical atherosclerosis varies by HIV status. The role of these biomarkers in CVD pathogenesis and risk prediction may be different in HIV-infected men.

ObjectiveTo examine whether altered levels of adipokines, adipose-derived peptides associated with myocardial infarction in the general population, may contribute to subclinical coronary atherosclerosis in HIV-infected persons.DesignNested cohort study.MethodsWe studied HIV-infected (HIV+) and HIV-uninfected (HIV-) men in the Multicenter AIDS Cohort Study with noncontrast computed tomography (CT) to measure coronary artery calcium and regional adiposity; 75% additionally underwent coronary CT angiography to measure plaque composition and stenosis. Adiponectin and leptin levels were assessed. Multiple regression models were used to assess associations between adipokine levels and HIV disease parameters, regional adiposity, and plaque adjusted for age, race, HIV serostatus, and cardiovascular disease (CVD) risk factors.ResultsSignificant findings were limited to adiponectin. HIV-positive men (n=493) had lower adiponectin levels than HIV-negative men (n=250) after adjusting for CVD risk factors (P

Testosterone, many steroidal androgens, and nonsteroidal ligands that bind to androgen receptor and exert tissue-specific transcriptional activity (selective androgen receptor modulators [SARMs]) are being developed as function-promoting therapies to treat functional limitations associated with aging and chronic diseases. This narrative review describes preclinical studies, mechanisms, and randomized trials of testosterone, other androgens, and nonsteroidal SARMs. Sex differences in muscle mass and strength and empiric use of anabolic steroids by athletes to increase muscularity and athletic performance provide supportive evidence of testosterone's anabolic effects. In randomized trials, testosterone treatment increases lean body mass, muscle strength, leg power, aerobic capacity, and self-reported mobility. These anabolic effects have been reported in healthy men, hypogonadal men, older men with mobility limitation and chronic diseases, menopausal women, and HIV-infected women with weight loss. Testosterone has not consistently improved walking speed. Testosterone treatment increases volumetric and areal bone mineral density, and estimated bone strength; improves sexual desire, erectile function, and sexual activity; modestly improves depressive symptoms; and corrects unexplained anemia in older men with low testosterone levels. Prior studies have not been of sufficient size or duration to determine testosterone's cardiovascular and prostate safety. The efficacy of testosterone in reducing physical limitations, fractures, falls, progression to diabetes, and correcting late-onset persistent depressive disorder remains to be established. Strategies to translate androgen-induced muscle mass and strength gains into functional improvements are needed. Future studies should evaluate the efficacy of combined administration of testosterone (or a SARM) plus multidimensional functional exercise to induce neuromuscular adaptations required for meaningful functional improvements. [ABSTRACT FROM AUTHOR]