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Supplemental Digital Content is Available in the Text. Background: The timing and magnitude of antiretroviral therapy–associated weight change attributions are unclear. Setting: HIV Outpatient Study participants. Methods: We analyzed 2007–2018 records of virally suppressed (VS) persons without integrase inhibitor (INSTI) experience who switched to either INSTI-based or another non–INSTI-based ART, and remained VS. We analyzed BMI changes using linear mixed models, INSTI- and tenofovir alafenamide (TAF) contributions to BMI change by linear mixed models–estimated slopes, and BMI inflection points. Results: Among 736 participants (5316 person-years), 441 (60%) switched to INSTI-based ART; the remainder to non–INSTI-based ART. The mean follow-up was 7.15 years for INSTI recipients and 7.35 years for non-INSTI. Preswitch, INSTI and non-INSTI groups had similar median BMI (26.3 versus 25.9 kg/m2, P = 0.41). INSTI regimens included raltegravir (178), elvitegravir (112), and dolutegravir (143). Monthly BMI increases postswitch were greater with INSTI than non-INSTI (0.0525 versus 0.006, P < 0.001). A BMI inflection point occurred 8 months after switch among INSTI users; slopes were similar regardless of TAF use immediately postswitch. Among INSTI + TAF users, during 8 months postswitch, 87% of BMI slope change was associated with INSTI use, 13% with TAF use; after 8 months, estimated contributions were 27% and 73%, respectively. For non-INSTI+TAF, 84% of BMI gain was TAF-associated consistently postswitch. Persons switching from TDF to TAF had greater BMI increases than others (P < 0.001). Conclusion: Among VS persons who switched ART, INSTI and TAF use were independently associated with BMI increases. During 8 months postswitch, BMI changes were greatest and most associated with INSTI use; afterward, gradual BMI gain was largely TAF-associated. [ABSTRACT FROM AUTHOR]

Polypharmacy is the concurrent use of five or more medications. We used group-based trajectory analysis to identify groups of non-HIV medication polypharmacy and investigate associated risk factors among HIV-positive and HIV-negative men in the Multicenter AIDS Cohort Study (MACS) from 2004 to 2016. Each participant was assigned to mutually exclusive groups based on their observed patterns of polypharmacy over time. Risk factors associated with membership with resulting groups were investigated using a multinomial generalized logit model with repeated measures. There were 3160 participants (54.3% HIV positive) included in the study. The overall prevalence of polypharmacy was 33.1% and was higher in HIV-positive than HIV-negative participants (36.2% vs. 30.0%; p < 0.001). Four distinct groups of polypharmacy emerged over time among all participants and among HIV-positive participants only: (1) nonpolypharmacy, (2) slow increasing polypharmacy, (3) rapid increasing polypharmacy, and (4) sustained polypharmacy. Being HIV positive, being 50 years of age or older, having medication insurance coverage, and having increased health care use were positively associated with membership in groups with sustained or increasing polypharmacy. Half of participants in each analysis had membership in one of the three high polypharmacy groups. This study revealed that access to care, through medication insurance coverage and health care use, was a key driver of polypharmacy in this cohort. Further exploration of medically appropriate and inappropriate prescribing practices in the context of polypharmacy and its impact on health outcomes in this and other populations is warranted. [ABSTRACT FROM AUTHOR]

Current U.S. guidelines recommend integrase strand transfer inhibitor (INSTI)-based antiretroviral therapy (ART) as initial treatment for people with HIV (PWH). We assessed long-term effects of INSTI use on lipid profiles in routine HIV care. We analyzed medical record data from the HIV Outpatient Study's participants in care from 2007 to 2021. Hyperlipidemia was defined based on clinical diagnoses, treatments, and laboratory results. We calculated hyperlipidemia incidence rates and rate ratios (RRs) during initial ART and assessed predictors of incident hyperlipidemia by using Poisson regression. Among 349 eligible ART-naïve PWH, 168 were prescribed INSTI-based ART (36 raltegravir (RAL), 51 dolutegravir (DTG), and 81 INSTI-others (elvitegravir and bictegravir)) and 181 non-INSTI-based ART, including 68 protease inhibitor (PI)-based ART. During a median follow-up of 1.4 years, hyperlipidemia rates were 12.8, 22.3, 22.7, 17.4, and 12.6 per 100 person years for RAL-, DTG-, INSTI-others-, non-INSTI-PI-, and non-INSTI-non-PI-based ART, respectively. In multivariable analysis, compared with the RAL group, hyperlipidemia rates were higher in INSTI-others (RR = 2.25; 95% confidence interval (CI): 1.29–3.93) and non-INSTI-PI groups (RR = 1.89; CI: 1.12–3.19) but not statistically higher for the DTG (RR = 1.73; CI: 0.95–3.17) and non-INSTI-non-PI groups (RR = 1.55; CI: 0.92–2.62). Other factors independently associated with hyperlipidemia included older age, non-Hispanic White race/ethnicity, and ART without tenofovir disoproxil fumarate. PWH using RAL-based regimens had lower rates of incident hyperlipidemia than PWH receiving non-INSTI-PI-based ART but had similar rates as those receiving DTG-based ART, supporting federal recommendations for using DTG-based regimens as the initial therapy for ART-naïve PWH. [ABSTRACT FROM AUTHOR]

Background There is limited evidence that among HIV-infected patients haemoglobin A1c (HbA1c) values may not accurately reflect glycaemia. We assessed HbA1c discordance (observed HbA1c − expected HbA1c) and associated factors among HIV-infected participants in the Multicenter AIDS Cohort Study (MACS). Methods Fasting glucose (FG) and HbA1c were measured at each semi-annual MACS visit since 1999. All HIV-infected and HIV-uninfected men for whom at least one FG and HbA1c pair measurement was available were evaluated. Univariate median regression determined the association between HbA1c and FG by HIV serostatus. The relationship between HbA1c and FG in HIV-uninfected men was used to determine the expected HbA1c. Generalized estimating equations determined factors associated with the Hb1Ac discordance among HIV-infected men. Clinically significant discordance was defined as observed HbA1c − expected HbA1c ≤−0.5%. Results Over 13 years, 1500 HIV-uninfected and 1357 HIV-infected men were included, with a median of 11 visits for each participant. At an FG of 125 mg/dL, the median HbA1c among HIV-infected men was 0.21% lower than among HIV-uninfected men and the magnitude of this effect increased with FG >126 mg/dL. Sixty-three percent of HIV-infected men had at least one visit with clinically significant HbA1c discordance, which was independently associated with: low CD4 cell count (<500 cells/mm3); a regimen containing a protease inhibitor, a non-nucleoside reverse transcriptase inhibitor or zidovudine; high mean corpuscular volume; and abnormal corpuscular haemoglobin. Conclusion HbA1c underestimates glycaemia in HIV-infected patients and its use in patients with risk factors for HbA1c discordance may lead to under-diagnosis and to under-treatment of established diabetes mellitus. [ABSTRACT FROM PUBLISHER]

Background Identifying factors associated with mortality for HIV-infected patients with persistent viraemia despite antiretroviral (ARV) therapy may inform diagnostic and treatment strategies. Methods We analysed data from viraemic triple-ARV-class-experienced HIV Outpatient Study patients seen during 1 January 1999 to 31 December 2012 who, despite treatment that included ARVs from three major drug classes [nucleoside analogue reverse transcriptase inhibitors, non-nucleoside analogue reverse transcriptase inhibitors and protease inhibitors (PIs)], had plasma HIV RNA levels [viral load (VL)] >1000 copies/mL [‘triple ARV class failure’ (TCF)]. The baseline was defined as the date of meeting the TCF criteria during 1999–2008. We identified factors associated with mortality using Cox regression. Results Of 597 patients who met the TCF criteria (median follow-up after baseline 4.9 years), 115 (19.3%) died. Baseline factors associated with mortality were age per 10 years [hazard ratio (HR) 1.61, 95% CI 1.28–2.02], risk of HIV from use of injection drugs (HR 1.81, 95% CI 1.10–2.98), CD4+ T cell count <200 cells/mm3 (HR 3.68, 95% CI 2.41–5.62), VL ≥5.0 log10 copies/mL (HR 2.91, 95% CI 1.88–4.49) and receiving a first combination ARV therapy regimen that was PI-based (HR 2.44, 95% CI 1.47–4.06); receiving a novel ARV agent during follow-up (HR 0.45, 95% CI 0.22–0.93) was protective. Genotypic resistance testing results were available for 274 (45.9%) of the TCF patients, of whom 47 (17.2%) died. In this group, factors associated with death were increasing age (HR 1.94, 95% CI 1.36–2.78, per 10 year increment), risk of HIV from use of injection drugs (HR 2.71, 95% CI 1.37–5.39), baseline VL ≥5.0 log10 copies/mL (HR 5.35, 95% CI 2.82–10.1) and receiving PI-based first combination ARV therapy regimen (HR 3.20, 95% CI 1.25–8.17). No HIV mutations or combinations of mutations were significantly associated with survival. Conclusions Factors significantly associated with mortality risk among TCF patients who received ongoing ARV therapy included traditional clinical predictors but not the presence, type or number of HIV genetic mutations. The use of novel ARV drugs by these ARV therapy-experienced patients was associated with an improved survival. [ABSTRACT FROM PUBLISHER]

Menopause may impact the earlier onset of aging-related comorbidities among women with versus without human immunodeficiency virus (HIV). We found that menopausal status, age, and HIV were independently associated with higher comorbidity burden, and that HIV impacted burden most in the pre-/perimenopausal phases. [ABSTRACT FROM AUTHOR]

The article reviews a visual art exhibition ArtAidsAmerica related to AIDS held at the Alphawood Gallery in Chicago, Illinois curated by curator of Tacoma Art Museum Rock Hushka and curator of University at Buffalo Jonathan David Katz.

The article presents a study which examines the heterologous fat transplant to treat facial lipoatrophy in a set of HIV-serodiscordant homozygous twins. Both patients have undergone standard pre-solid organ transplantation assessments. The fat transplantation for HIV-related facial lipoatrophy seems to be a safe and effective treatment that can result in aesthetic improvements and greater patient satisfaction.

Background National guidelines recommend that sexually active people with human immunodeficiency virus (PWH) who are men who have sex with men (MSM) be tested for hepatitis C virus (HCV) infection at least annually. Hepatitis C virus testing rates vary by race/ethnicity in the general population, but limited data are available for PWH. Methods We analyzed medical records data from MSM in the HIV Outpatient Study at 9 human immunodeficiency virus (HIV) clinics from January 1, 2011 through December 31, 2019. We excluded observation time after documented past or current HCV infection. We evaluated HCV antibody testing in each calendar year among HCV-seronegative MSM, and we assessed testing correlates by generalized estimating equation analyses. Results Of 1829 eligible MSM who were PWH, 1174 (64.2%) were non-Hispanic/Latino white (NHW), 402 (22.0%) non-Hispanic black (NHB), 187 (10.2%) Hispanic/Latino, and 66 (3.6%) of other race/ethnicity. Most were ≥40 years old (68.9%), privately insured (64.5%), with CD4 cell count/mm3 (CD4) ≥350 (77.0%), and with HIV viral load <200 copies/mL (76.9%). During 2011–2019, 1205 (65.9%) had ≥1 HCV antibody test and average annual HCV percentage tested was 30.3% (from 33.8% for NHB to 28.5% for NHW; P <.001). Multivariable factors positively associated (P <.05) with HCV testing included more recent HIV diagnosis, public insurance, lower CD4, prior chlamydia, gonorrhea, syphilis, or hepatitis B virus diagnoses, and elevated liver enzyme levels, but not race/ethnicity. Conclusions Although we found no disparities by race/ethnicity in HCV testing, low overall HCV testing rates indicate suboptimal uptake of recommended HCV testing among MSM in HIV care. [ABSTRACT FROM AUTHOR]

Background Although chlamydia (CT) and gonorrhea (GC) infections are increasing in the United States, there are limited data on their incidence, testing rates, and associated risk factors among persons living with HIV (PLWH), including by anatomic site among men who have sex with men (MSM). Methods We analyzed 2007–2017 medical records data from Human Immunodeficiency Virus (HIV) Outpatient Study (HOPS) participants in care at 9 HIV clinics. We calculated CT (and GC) incidence and testing rates and assessed associations with sociodemographic and clinical factors using log-linear regression. Results Among 4727 PLWH, 397 had 881 CT infections and 331 had 861 GC infections, with an incidence of 2.95 and 2.88 per 100 person-years, respectively. From 2007 to 2017, incidence and testing rates increased by approximately 3.0- and 1.9-fold for CT and GC, respectively. Multivariable factors associated with incident CT (GC) included younger age, MSM, and prior diagnoses of sexually transmitted diseases (STDs). Among 1159 MSM, 583 (50.3%) had 844 CT and 843 GC tests during 2016–2017, and 26.6% of tests were 3-site (urethra, rectum, and pharynx), yielding the highest rates of CT (GC) detection. Multivariable factors associated with CT (GC) testing included younger age, non-Hispanic/Latino black race, and having prior STDs. Conclusions Recent CT and GC incidence and testing increased among PLWH; however, only half of MSM were tested for CT or GC during 2016–2017 and less than a third of tests were 3-site. To promote sexual health and STD prevention among PLWH who are MSM, research regarding the added value of CT and GC testing across 3 anatomic sites is needed. [ABSTRACT FROM AUTHOR]

Background The clinical epidemiology of treated HIV infection in the United States has dramatically changed in the past 25 years. Few sources of longitudinal data exist for people with HIV (PWH) spanning that period. Cohort data enable investigating new exposure and disease associations and monitoring progress along the HIV care continuum. Methods We synthesized key published findings and conducted primary data analyses in the HIV Outpatient Study (HOPS), an open cohort of PWH seen at public and private HIV clinics since 1993. We assessed temporal trends in health outcomes (1993–2017) and mortality (1994–2017) for 10 566 HOPS participants. Results The HOPS contributed to characterizing new conditions (eg, lipodystrophy), demonstrated reduced mortality with earlier HIV treatment, uncovered associations between select antiretroviral agents and cardiovascular disease, and documented remarkable shifts in morbidity from AIDS opportunistic infections to chronic noncommunicable diseases. The median CD4 cell count of participants increased from 244 cells/mm3 to 640 cells/mm3 from 1993 to 2017. Mortality fell from 121 to 16 per 1000 person-years from 1994 to 2017 (P  < .001). In 2010, 83.7% of HOPS participants had a most recent HIV viral load <200 copies/mL, compared with 92.2% in 2017. Conclusions Since 1993, the HOPS has been detecting emerging issues and challenges in HIV disease management. HOPS data can also be used for monitoring trends in infectious and chronic diseases, immunologic and viral suppression status, retention in care, and survival, thereby informing progress toward the Ending the HIV Epidemic initiative. [ABSTRACT FROM AUTHOR]

Background: People living with human immunodeficiency virus (HIV+) have greater risk for sudden arrhythmic death than HIV-uninfected (HIV-) individuals. HIV-associated abnormal cardiac repolarization may contribute to this risk. We investigated whether HIV serostatus is associated with ventricular repolarization lability by using the QT variability index (QTVI), defined as a log measure of QT-interval variance indexed to heart rate variance.Methods: We studied 1123 men (589 HIV+ and 534 HIV-) from MACS (Multicenter AIDS Cohort Study), using the ZioXT ambulatory electrocardiography patch. Beat-to-beat analysis of up to 4 full days of electrocardiographic data per participant was performed using an automated algorithm (median analyzed duration [quartile 1-quartile 3]: 78.3 [66.3-83.0] hours/person). QTVI was modeled using linear mixed-effects models adjusted for demographics, cardiac risk factors, and HIV-related and inflammatory biomarkers.Results: Mean (SD) age was 60.1 (11.9) years among HIV- and 54.2 (11.2) years among HIV+ participants (P<0.001), 83% of whom had undetectable (<20 copies/mL) HIV-1 viral load (VL). In comparison with HIV- men, HIV+ men had higher QTVI (adjusted difference of +0.077 [95% CI, +0.032 to +0.123]). The magnitude of this association depended on the degree of viremia, such that in HIV+ men with undetectable VL, adjusted QTVI was +0.064 (95% CI, +0.017 to +0.111) higher than in HIV- men, whereas, in HIV+ men with detectable VL, adjusted QTVI was higher by +0.150 (95% CI, 0.072-0.228) than in HIV- referents. Analysis of QTVI subcomponents showed that HIV+ men had: (1) lower heart rate variability irrespective of VL status, and (2) higher QT variability if they had detectable, but not with undetectable, VL, in comparison with HIV- men. Higher levels of C-reactive protein, interleukin-6, intercellular adhesion molecule-1, soluble tumor necrosis factor receptor 2, and soluble cluster of differentiation-163 (borderline), were associated with higher QTVI and partially attenuated the association with HIV serostatus.Conclusions: HIV+ men have greater beat-to-beat variability in QT interval (QTVI) than HIV- men, especially in the setting of HIV viremia and heightened inflammation. Among HIV+ men, higher QTVI suggests ventricular repolarization lability, which can increase susceptibility to arrhythmias, whereas lower heart rate variability signals a component of autonomic dysfunction. [ABSTRACT FROM AUTHOR]

Background: During the COVID-19 pandemic, telemedicine was adopted to ensure continuity of HIV care. We examined how introducing televisits affected technical quality of care for people with HIV (PWH) during this time. Methods: PWH receiving HIV care at Howard Brown Health Centers and Northwestern University in Chicago, Illinois were included. HIV care quality indicators were calculated using data extracted from electronic medical records during 4 timepoints every 6 months from March, March 1, 2020 to September 1, 2021. Generalized linear mixed models estimated differences in indicators across timepoints within each site while controlling for multiple observations of individuals. Generalized linear mixed models were also used to compare differences in outcomes among PWH who attended all versus a combination of in-person and televisits versus no televisits across the study time periods. Results: 6447 PWH were included in the analysis. Compared with prepandemic levels, there were significant declines in care utilization and processes of care measures. Measures of HIV virologic suppression, blood pressure control, and HbA1C,7% (in both people with and without diabetes) were stable with no significant differences noted across the study timepoints. Similar trends were observed across all age, race, and sex subgroups. In multivariable models, televisits were not associated with decreased HIV viral suppression. Conclusions: During the COVID-19 pandemic and rapid implementation of televisits, indicators of care utilization and processes of care decreased compared with prepandemic levels. Among PWH who remained in care, televisits were not associated with worse virologic, blood pressure, and glycemic control in PWH. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) is an important cause of morbidity and mortality among HIV-infected adults. Calculating an individual's excess heart age, or the difference between their chronological age and predicted heart age, can be useful in describing their risk for developing CVD and motivating behavior change to decrease their CVD risk. The overall mean excess heart age is 7.8 and 5.4 years among U.S. men and women, respectively. We evaluated excess heart age among HIV-infected adults in medical care using sex-specific, cholesterol-based models developed from Framingham general CVD risk prediction equations. Included were HIV Outpatient Study (HOPS) participants aged 30-74 y, who had ≥2 HOPS clinic visits during 2010-2014, had no prior CVD at the start of observation, had >1 y of follow-up, and had non-missing data for all covariates. Age-standardized (2010 U.S. census) and weighted means, prevalence and 95% confidence intervals (CIs) were calculated for participant chronological age, predicted heart age, and excess heart age. From 5,088 HOPS participants assessed for eligibility, 1905 men and 584 women were included in the analysis. Heart age exceeded chronological age by 11.3 and 11.9 y among men and women, respectively (Table). Excess heart age was greatest among non-Hispanic Blacks, persons aged 50-59 y, those with less than high school education, and women with a median CD4+ count ≥500 cells/μL. Predicted heart age was higher than chronological age among HIV-infected men and women and surpassed excess heart age estimates observed in the general U.S. population. Greater excess heart age among HIV-infected adults might result from demographic differences, higher frequency of CVD risk factors including smoking, diabetes, HIV-associated excess chronic inflammation, and possibly lower use rates of antihypertensive or statin drugs. Routine clinical use of heart age calculation may help optimize CVD risk communication and interventions for aging HIV-infected persons. [ABSTRACT FROM AUTHOR]

Background. Increasing body mass index (BMI) is generally associated with loss of metabolic health, although some obese individuals remain metabolically healthy. Among nonobese men, HIV infection has been associated with a lower prevalence of metabolic health. Methods. We conducted a cross-sectional analysis of 470 HIV-infected and 368 HIV-uninfected men enrolled in the Multicenter AIDS Cohort Study Cardiovascular substudy. Circulating biomarker levels were compared by BMI category and by HIV serostatus. Poisson regression with robust variance determined associations between metabolic health and circulating inflammatory biomarker levels after adjusting for factors previously associated with metabolic health. Results. HIV-infected men were younger and less likely to be obese. Among HIV-infected, normal weight metabolically healthy men (compared to unhealthy) had significantly lower circulating levels of interleukin- (IL-) 6, soluble tumor necrosis factor receptors (sTNFR) I and II, and homeostatic model assessment of insulin resistance (HOMA-IR), higher adiponectin, less visceral fat, and more subcutaneous fat. Among HIV-uninfected normal weight men and obese men (regardless of HIV serostatus), metabolic health was associated only with higher levels of adiponectin, less visceral fat, and lower HOMA-IR values. In multivariate analyses restricted to HIV-infected men, lower hs-CRP, sTNFRI, sTNFRII, and HOMA-IR and higher adiponectin levels were associated with metabolic health. Additional adjustment for visceral adiposity did not alter results. Conclusions. Among HIV-infected normal weight men, metabolic health was associated with less systemic inflammation, a relationship that, among normal weight men, was unique to HIV+ men and did not exist among obese men of either HIV serostatus. [ABSTRACT FROM AUTHOR]

Background We sought to characterize in people with human immunodeficiency virus (PWH) the potential etiologies of elevated alanine aminotransferase (ALT) levels, which are common and often unexplained. Methods Participants from the longitudinal observational AIDS Clinical Trials Group HAILO cohort without a history of hepatitis C virus (HCV) or hepatitis B virus (HBV) infection nor reported heavy alcohol use were included. Clinical and demographic characteristics, including medication use, the hepatic steatosis index (HSI), and metabolic syndrome (MetS) were compared between participants with and without ALT elevation. Results Six hundred sixty-two participants were included; 444 (67%) had ≥1 and 229 (35%) ≥2 consecutive ALT elevations during a median of 4.0 years of follow-up. HSI and Hispanic or other (non-White or Black) race/ethnicity were consistently associated with higher odds of abnormal ALT (odds ratio [OR] 1.1 for HSI as a continuous variable, OR 1.9–2.8 for Hispanic/other race/ethnicity for ≥1 or ≥2 ALT elevations); older age and current smoking were associated with lower odds of abnormal ALT. Associations with metabolic disease, as well as with incident HBV and HCV infection, were strengthened by restricting outcomes to persistent and higher degrees of ALT elevation. Conclusions ALT elevation was common in this cohort of PWH and associated with metabolic disease and hepatic steatosis markers. Nonalcoholic fatty liver disease is likely a common cause of liver inflammation in PWH receiving suppressive antiretrovirals, deserving targeted diagnosis and intervention. [ABSTRACT FROM AUTHOR]

Background To evaluate the effect of cumulative human immunodeficiency virus (HIV)-1 viremia on aging-related multimorbidity among women with HIV (WWH), we analyzed data collected prospectively among women who achieved viral suppression after antiretroviral therapy (ART) initiation (1997–2019). Methods We included WWH with ≥2 plasma HIV-1 viral loads (VL) <200 copies/mL within a 2-year period (baseline) following self-reported ART use. Primary outcome was multimorbidity (≥2 nonacquired immune deficiency syndrome comorbidities [NACM] of 5 total assessed). The trapezoidal rule calculated viremia copy-years (VCY) as area-under-the-VL-curve. Cox proportional hazard models estimated the association of time-updated cumulative VCY with incident multimorbidity and with incidence of each NACM, adjusting for important covariates (eg, age, CD4 count, etc). Results Eight hundred six WWH contributed 6368 women-years, with median 12 (Q1–Q3, 7–23) VL per participant. At baseline, median age was 39 years, 56% were Black, and median CD4 was 534 cells/mm3. Median time-updated cumulative VCY was 5.4 (Q1–Q3, 4.7–6.9) log10 copy-years/mL. Of 211 (26%) WWH who developed multimorbidity, 162 (77%) had incident hypertension, 133 (63%) had dyslipidemia, 60 (28%) had diabetes, 52 (25%) had cardiovascular disease, and 32 (15%) had kidney disease. Compared with WWH who had time-updated cumulative VCY <5 log10, the adjusted hazard ratio of multimorbidity was 1.99 (95% confidence interval [CI], 1.29–3.08) and 3.78 (95% CI, 2.17–6.58) for those with VCY 5–6.9 and ≥7 log10 copy-years/mL, respectively (P <.0001). Higher time-updated cumulative VCY increased the risk of each NACM. Conclusions Among ART-treated WWH, greater cumulative viremia increased the risk of multimorbidity and of developing each NACM, and hence this may be a prognostically useful biomarker for NACM risk assessment in this population. [ABSTRACT FROM AUTHOR]

Background: Osteoporosis is common among HIV-infected persons and contributes to risk of fragility fracture. While ART initiation is associated with decreases in bone mineral density and increases in bone turnover, the impact of HIV on bone metabolism is unclear.Methods: We identified men at the Chicago site of the Multicenter AIDS Cohort Study who HIV seroconverted while under observation. Concentrations of 25-OH vitamin D, bone turnover markers [procollagen type 1 N terminal propeptide (P1NP), osteocalcin (OC), C-telopeptide (CTX)] and sclerostin were measured from stored serum obtained at pre-HIV infection, pre-ART and post-ART initiation timepoints. Mixed models, with each biomarker as an outcome, were fitted. Timepoint, age, CD4 count (cells/mm 3 ), HIV-viral suppression, season and an age by timepoint interaction term were considered as fixed effects.Results: Data from 52 participants revealed that median duration between HIV seroconversion and ART initiation was 8.7 years (IQR 3.7-11.6). Median CD4 and plasma HIV-RNA concentrations were 445 (IQR 298.5-689) and 20 184 copies/mL (IQR 6237-64 340), respectively, at the pre-ART timepoint. Multivariate analyses demonstrated pre-HIV infection levels of OC that were higher than pre-ART levels (6.8 versus 5.7 ng/mL, P  =   0.04); and pre-ART levels of sclerostin that were higher than post-ART levels (0.033 versus 0.02 ng/mL, P  <0.001). No changes in P1NP, CTX and 25-OH vitamin D levels were detected.Conclusions: HIV seroconversion was associated with decreased OC levels while ART initiation was associated with decreases in sclerostin, a negative regulator of bone formation. Our results suggest that both HIV infection and ART have an impact on bone metabolism in white men. [ABSTRACT FROM AUTHOR]

Background: We characterized trends in statin eligibility and subsequent statin initiation among people with HIV (PWH) from 2001 to 2017 and identified predictors of statin initiation between 2014 and 2017. Setting: PWH participating in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) enrolled in 12 US cohorts collecting data on statin eligibility criteria/prescriptions from 2001 to 2017. Methods: We determined the annual proportion eligible for statins, initiating statins, and median waiting time (from statin eligibility to initiation). Eligibility was defined using ATP III guidelines (2001–2013) and ACC/AHA guidelines (2014–2017). We assessed initiation predictors in 2014–2017 among statin-eligible PWH using Poisson regression, estimating adjusted prevalence ratios (aPRs) with 95% confidence intervals (95% CIs). Results: Among 16,409 PWH, 7386 (45%) met statin eligibility criteria per guidelines (2001–2017). From 2001 to 2013, statin eligibility ranged from 22% to 25%. Initiation increased from 13% to 45%. In 2014, 51% were statin-eligible, among whom 25% initiated statins, which increased to 32% by 2017. Median waiting time to initiation among those we observed declined over time. Per 10-year increase in age, initiation increased 46% (aPR 1.46, 95% CI: 1.29 to 1.67). Per 1-year increase in calendar year from 2014 to 2017, there was a 41% increase in the likelihood of statin initiation (aPR 1.41, 95% CI: 1.25 to 1.58). Conclusions: There is a substantial statin treatment gap, amplified by the 2013 ACC/AHA guidelines. Measures are warranted to clarify reasons we observe this gap, and if necessary, increase statin use consistent with guidelines including efforts to help providers identify appropriate candidates. [ABSTRACT FROM AUTHOR]

Insights into combination HIV prevention (CHP) strategies to reduce HIV incidence among midlife and older adult men who have sex with men (MSM) are limited. The current study is a secondary data analysis evaluating CHP in a sample of sexually active midlife and older adult MSM (N = 566) from the Multicenter AIDS Cohort Study Healthy Aging Substudy. Stratified by HIV serostatus, we used latent class analyses to identify CHP classes based on self-reported sociobehavioral and biobehavioral prevention strategies that participants and their male partners used in the prior 6 months. We identified three CHP classes among men living without HIV (MLWOH), including the following: high CHP overall (43.0%), high anal sex abstention (15.0%), and low prevention overall (42.0%). Among men living with HIV (MLWH), we identified four CHP classes, including the following: high CHP overall (20.9%), high CHP/low condom use (27.1%), high condom reliance (22.3%), and low prevention overall (29.7%). There were small differences by sociodemographic characteristics and sexual behavior practices between the classes; however, poppers use was often linked to being in high CHP groups. Our findings support that CHP is not one-size-fits-all for midlife and older adult MSM. There remains a need to scale up clinical providers' sexual health communication practices to assist midlife and older MSM incorporate prevention strategies, particularly biobehavioral prevention strategies that align with their patients' lived experiences. [ABSTRACT FROM AUTHOR]

Background: and Methods National surveillance data show recent, marked reductions in morbidity and mortality associated with the acquired immunodeficiency syndrome (AIDS). To evaluate these declines, we analyzed data on 1255 patients, each of whom had at least one CD4+ count below 100 cells per cubic millimeter, who were seen at nine clinics specializing in the treatment of human immunodeficiency virus (HIV) infection in eight U.S. cities from January 1994 through June 1997. Results: Mortality among the patients declined from 29.4 per 100 person-years in 1995 to 8.8 per 100 person-years in the second quarter of 1997. There were reductions in mortality regardless of sex, race, age, and risk factors for transmission of HIV. The incidence of any of three major opportunistic infections (Pneumocystis carinii pneumonia, Mycobacterium avium complex disease, and cytomegalovirus retinitis) declined from 21.9 per 100 person-years in 1994 to 3.7 per 100 person-years by mid-1997. In a failure-rate model, increases in the intensity of antiretroviral therapy (classified as none, monotherapy, combination therapy without a protease inhibitor, and combination therapy with a protease inhibitor) were associated with stepwise reductions in morbidity and mortality. Combination antiretroviral therapy was associated with the most benefit; the inclusion of protease inhibitors in such regimens conferred additional benefit. Patients with private insurance were more often prescribed protease inhibitors and had lower mortality rates than those insured by Medicare or Medicaid. Conclusions: The recent declines in morbidity and mortality due to AIDS are attributable to the use of more intensive antiretroviral therapies. (N Engl J Med 1998;338:853-60.) [ABSTRACT FROM AUTHOR]

People 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. We 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. The 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. Coronary 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. [Display omitted] • The extent of HIV viremia and traditional CVD risk factors is associated with progression of coronary artery stenosis. • Improved adherence to combination antiretroviral therapy may mitigate this increased risk. • Disparities exist in control of HIV viremia, which require thoughtful interventions. [ABSTRACT FROM AUTHOR]

Examine prospective relationships between erectile dysfunction (ED) drugs and CD4 and CD8 T-cells, and immune markers among men who have sex with men (MSM). Data from Multicenter AIDS Cohort Study, an observational prospective cohort study, with semiannual follow-ups conducted in four U.S. centers from 1998 onwards was used. Marginal structural models using g-computation were 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. Total 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 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. Long-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. [ABSTRACT FROM AUTHOR]

The ability of virally suppressive antiretroviral therapy use to extend the life span of people with HIV (PWH) implies that the age of PWH will also increase. Among PWH, extended survival comes at a cost of earlier onset and increased rates of aging-associated comorbidities and geriatric syndromes, with persistent inflammation and immune dysregulation consequent to chronic HIV infection and to antiretroviral therapy use contributing to an overall decrease in health span. The geroscience hypothesis proposes that the root causes of most aging-related chronic diseases and conditions is the aging process itself. Hence, therapeutically targeting fundamental aging processes could have a greater impact on alleviating or delaying aging-associated comorbidities than addressing each disease individually. Extending the geroscience hypothesis to PWH, we speculate that targeting basic mechanisms of aging will improve overall health with age. Clinical features and pathophysiologic mechanisms of chronic diseases in PWH qualitatively resemble those seen in older adults without HIV. Therefore, drugs that target any of the pillars of aging, including metformin, rapamycin, and nicotinamide adenine dinucleotide precursors, may also slow the rate of onset of age-associated comorbidities and geriatric syndromes in PWH. Drugs that selectively induce apoptosis of senescent cells, termed senolytics, may also improve health span among PWH. Preliminary evidence suggests that senescent cell burden is increased in PWH, implying that senescent cells are an excellent therapeutic target for extending health span. Recently initiated clinical trials evaluating senolytics in age-related diseases offer insights into the design and potential implementation of similar trials for PWH. [ABSTRACT FROM AUTHOR]

Background Hypogonadism is common among HIV-infected men, even among men receiving antiretroviral therapy (ART). Our objective in this study was to determine the prevalence of biochemical hypogonadism among HIV-infected men compared with HIV-uninfected controls. We also examined the use of free testosterone (FT) and total testosterone (TT) measurements in the assessment of biochemical hypogonadism in HIV-infected and - uninfected men. Methods This was a cross-sectional analysis from the Multicenter AIDS Cohort Study (MACS). TT levels were measured from archived serum using liquid chromatography-tandem mass spectrometry. FT was calculated from TT and sex hormone binding globulin (SHBG) (measured by radioimmunoassay) using the Vermeulen equation. Biochemical hypogonadism was defined as having low TT, low FT, or both. Results Of 945 men in the MACS Cardiovascular Substudy, T assays were not performed in 89 because of insufficient/no stored serum (n = 18) or use of T replacement therapy (TRT) (n = 71). 530 men had morning (AM) T measurements; 364 (68.7%) were HIV-infected. The prevalence of biochemical hypogonadism was similar in HIV-infected (34/364 = 9.3%) and HIV-uninfected (12/166 = 7.2%) men. Prevalence of hypogonadism, when men on TRT (n = 71) were included in the group of hypogonadal men, was higher in HIV-infected (104/434 = 24.0%) compared with HIV-uninfected (13/167 = 7.8%) men (p < 0.0001). Of 34 HIVinfected men with biochemical hypogonadism not on TRT, 11 (32.4%) had normal TT, but low FT. Of 12 HIV-uninfected men with biochemical hypogonadism not on TRT, none were in this category (p = 0.04) - all had low TT. Conclusions The prevalence of biochemical hypogonadism in our sample of HIV-infected men was approximately 10%, with a substantial proportion of these men having a normal TT, but low FT. The measurement of AM FT, rather than TT, in the assessment of hypogonadism in HIVinfected men will likely increase diagnostic sensitivity and should be recommended. [ABSTRACT FROM AUTHOR]

Objectives Connections to the gay community may elicit negative self-appraisals among men who have sex with men (MSM), which may be exacerbated for people with HIV (PWH). Fitness engagement may mediate self-appraisals by maintaining or improving appearance and health. We hypothesized that gay community connections would be positively related to negative self-appraisal and explored whether this association would be mediated by fitness engagement and moderated by HIV status. Method Data were obtained from the Multicenter AIDS Cohort Healthy Aging study (N = 1,026; PWH n = 525; people without HIV [PWOH] n = 501). Structural equation modeling (SEM) examined associations between gay community connections, negative self-appraisal (body image dissatisfaction, self-perception of aging), and fitness engagement (physical activity, motivation to be fit). Multiple-group SEM tested the moderating effects of HIV serostatus. Results The SEM fit the data well (root mean square error of approximation = 0.056; 90% CI: 0.046, 0.066). Connection to the gay community was inversely related to negative self-appraisals and positively related to fitness engagement. Fitness engagement mediated the association between community connections and negative self-appraisal and was inversely related to negative self-appraisals. Among PWH, the association between community connections and self-appraisal was weaker and the effect of fitness engagement on negative self-appraisal was stronger compared to PWOH. Discussion Connection to the gay community may be a source of resilience for aging MSM by lessening negative self-appraisals and promoting strategies that address body image dissatisfaction and self-perceptions of aging. Interventions facilitating connections to the gay community may support healthy aging in this population. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is Available in the Text. Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) symptoms among people living with HIV (PLWH) are not well described. Setting: Longitudinal survey within the MACS/WIHS Combined Cohort Study (MWCCS) of PLWH compared with similar HIV-seronegative (SN) individuals. Methods: Telephone-administered survey of MWCCS participants at 13 clinical research sites across the United States addressing COVID-19 symptoms, SARS-CoV-2 testing, and pandemic impact on social distancing and antiretroviral therapy (ART) use. Primary data collection occurred during May (wave 1), June–July (wave 2), and August–September, 2020 (wave 3). Results: One-third of MWCCS participants were tested for SARS-CoV-2 infection; 10% was tested ≥2 times. Similar proportions of PLWH and SN participants were tested, but SARS-CoV-2 positivity was higher among PLWH than among SN individuals (9.4% vs 4.8%, P = 0.003). Odds of SARS-CoV-2 positivity remained higher among PLWH after adjusting for age, sex, race/ethnicity, and study site (adjusted odds ratio = 2.0, 95% confidence interval = 1.2 to 3.2). SARS-CoV-2 positivity was not associated with CD4 cell counts among PLWH. Among SARS-CoV-2 positive participants, 9% had no symptoms, 7% had 1–2 mild symptoms, and 84% had ≥3 symptoms. Most of the (98%) participants reported physical distancing during all survey waves; self-reported ART adherence among PLWH was not adversely affected during the pandemic compared with the previous year (similar adherence in 89% of participants, improved in 9% of participants, and decreased in 2% of participants). Conclusions: Despite similar SARS-CoV-2 testing and physical distancing profiles by HIV serostatus among MWCCS participants, PLWH who reported SARS-CoV-2 testing were more likely to have a positive test result. Additional studies are needed to determine whether and why PLWH are at increased risk of SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

Background. It is unclear if CD4 cell counts at HIV diagnosis have improved over a 10-year period of expanded HIV testing in the USA. Methods. We studied HOPS participants diagnosed with HIV infection ⩽6 months prior to entry into care during 2000- 2009. We assessed the correlates of CD4 count <200 cells/mm3 at HIV diagnosis (late HIV diagnosis) by logistic regression. Results. Of 1,203 eligible patients, 936 (78%) had a CD4 count within 3 months after HIV diagnosis. Median CD4 count at HIV diagnosis was 299 cells/mm3 and did not significantly improve over time (P = 0.13). Comparing periods 2000-2001 versus 2008-2009, respectively, 39% and 35% of patients had a late HIV diagnosis (P = 0.34). Independent correlates of late HIV diagnosis were having an HIV risk other than being MSM, age ⩾35 years at diagnosis, and being of nonwhite race/ethnicity. Conclusions. There is need for routine universal HIV testing to reduce the frequency of late HIV diagnosis and increase opportunity for patient- and potentially population-level benefits associated with early antiretroviral treatment. [ABSTRACT FROM AUTHOR]

Background. Excess mortality has decreased among human immunodeficiency virus (HIV)-infected patients but without evidence of a decrease among patients with AIDS. We assessed temporal changes in excess mortality and elucidated risk factors for excess mortality in patients with AIDS diagnosed in the era of highly active antiretroviral therapy (HAART). Methods. We included 1188 patients of the Longitudinal Study of Ocular Complications in AIDS who were aged 25-64 years at enrollment and who received a diagnosis of AIDS after 1995. We calculated excess mortality as the age-, year-, and sex-adjusted difference in mortality rates between patients with AIDS and persons in the US general population during the period 1999-2007. We used a relative survival model to identify risk factors for excess mortality. Results. There were a mean of 50 excess deaths per 1000 person-years (95% confidence interval [CI], 44-57 excess deaths per 1000 person-years) during 1999-2007. Excess mortality almost halved, with an annual decrease of 8.0% per year (95% CI, 3.0%-12.7%; P = .002) but remained high at 36 excess deaths per 1000 person-years in 2007. Viral load >400 copies/mL (compared with ⩽400 copies/mL; risk ratio, 3.4; 95% CI, 2.3-5.0), CD4+ count <200 cells/μL (compared with ⩾200 cells/μL; risk ratio, 2.7; 95% CI, 1.9-3.9), and cytomegalovirus retinitis (risk ratio, 1.6; 95% CI, 1.2-2.1) were the strongest risk factors for excess mortality. Conclusions. Excess mortality among patients with AIDS was nearly halved in the HAART era and most strongly linked to stage of HIV disease. These results reflect the continuing improvements in AIDS management but also highlight that excess mortality remains ∼5 times higher in patients with AIDS than in HIV-infected patients without AIDS. [ABSTRACT FROM AUTHOR]

Background Human immunodeficiency virus (HIV) infection may accelerate development of aging-related non-AIDS comorbidities (NACMs). The incidence of NACMs is poorly characterized among women living with HIV (WLWH). Methods WLWH and HIV-seronegative participants followed in the Women's Interagency HIV Study (WIHS) through 2009 (when >80% of WLWH used antiretroviral therapy) or onward were included, with outcomes measured through 31 March 2018. Sociodemographics, clinical covariates, and prevalent NACM were determined at enrollment. We used Poisson regression models to determine incident NACM burden (number of NACMs accrued through most recent WIHS visit out of 10 total NACMs assessed) by HIV serostatus and age. Results There were 3129 participants (2239 WLWH, 890 HIV seronegative) with 36 589 person-years of follow-up. At enrollment, median age was 37 years, 65% were black, and 47% currently smoked. In fully adjusted analyses, WLWH had a higher incident NACM rate compared with HIV-seronegative women (incidence rate ratio, 1.36 [95% confidence interval (CI), 1.02–1.81]). Incident NACM burden was higher among WLWH vs HIV-seronegative women in most age strata (HIV × age interaction: P  = .0438), and women <25 years old had the greatest incidence rate ratio by HIV serostatus at 1.48 (95% CI, 1.19–1.84) compared with those in older age groups. Incident NACM burden was associated with traditional comorbidity risk factors but not HIV-specific indices. Conclusions Incident NACM burden was higher among WLWH than HIV-seronegative women. This difference was most dramatic among women aged <25 years, a group for whom routine comorbidity screening is not prioritized. Established non-HIV comorbidity risk factors were significantly associated with incident NACM burden. More data are needed to inform best practices for NACM screening, prevention, and management among WLWH, particularly young women. [ABSTRACT FROM AUTHOR]

Background Integrase strand transfer inhibitor (INSTI)–based combination antiretroviral therapy (cART) is associated with greater weight gain among persons with human immunodeficiency virus (HIV), though metabolic consequences, such as diabetes mellitus (DM), are unclear. We examined the impact of initial cART regimen and weight on incident DM in a large North American HIV cohort (NA-ACCORD). Methods cART-naive adults (≥18 years) initiating INSTI-, protease inhibitor (PI)–, or nonnucleoside reverse transcriptase inhibitor (NNRTI)–based regimens from January 2007 through December 2017 who had weight measured 12 (±6) months after treatment initiation contributed time until clinical DM, virologic failure, cART regimen switch, administrative close, death, or loss to follow-up. Multivariable Cox regression yielded adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for incident DM by cART class. Mediation analyses, with 12-month weight as mediator, similarly adjusted for all covariates. Results Among 22 884 eligible individuals, 47% started NNRTI-, 30% PI-, and 23% INSTI-based cART with median follow-up of 3.0, 2.3, and 1.6 years, respectively. Overall, 722 (3%) developed DM. Persons starting INSTIs vs NNRTIs had incident DM risk (HR, 1.17 [95% CI,.92–1.48]), similar to PI vs NNRTI initiators (HR, 1.27 [95% CI, 1.07–1.51]). This effect was most pronounced for raltegravir (HR, 1.42 [95% CI, 1.06–1.91]) vs NNRTI initiators. The INSTI–DM association was attenuated (HR, 1.03 [95% CI,.71–1.49] vs NNRTIs) when accounting for 12-month weight. Conclusions Initiating first cART regimens with INSTIs or PIs vs NNRTIs may confer greater risk of DM, likely mediated through weight gain. [ABSTRACT FROM AUTHOR]

Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) coinfection carries substantial risk for all-cause mortality and liver-related morbidity and mortality, yet many persons coinfected with HIV/HCV remain untreated for HCV. We explored demographic, clinical, and sociodemographic factors among participants in routine HIV care associated with prescription of direct-acting antivirals (DAAs). The HIV Outpatient Study (HOPS) is an ongoing longitudinal cohort study of persons with HIV in care at participating clinics since 1993. There are currently eight study sites in six US cities. We analyzed medical records data of HOPS participants diagnosed with HCV since June 2010. Sustained virological response (SVR) was documented with first undetectable HCV viral load (VL). We assessed factors associated with being prescribed DAAs by multi-variable logistic regression and described the cumulative rate of SVR. Among 306 eligible participants, 131 (43%) were prescribed DAA therapy. Factors associated with greater odds of being prescribed DAA were older age, private health insurance, higher CD4 cell count, being a person who injects drugs, and receiving care at publicly funded sites (p < 0.05). Of 127 (97%) participants with at least 1 follow-up HCV VL, 110 (87%) achieved SVR at 12 weeks. Of the total 131 participants, 123 (94%) eventually achieved SVR. Less than half of HIV/HCV coinfected patients in HOPS have been prescribed DAAs. Interventions are needed to address deficits in DAA prescription, including among patients with public or no health insurance, younger age, and lower CD4 cell count. [ABSTRACT FROM AUTHOR]

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 <.001). Associations among MSM without HIV were similar, with average marijuana use (r =.19) and stimulant use (r =.22) being positively correlated with average ED drug use, and were also correlated with having multiple partners (r =.36), insertive anal intercourse with condom (r =.22), and insertive anal intercourse without condom (r =.18) over time. Positive within-individual associations between ED drug use and multiple partners and insertive anal intercourse with and without condom were observed regardless of HIV serostatus. This study showed that MSM who reported use of ED drugs were also, on average, more likely to use recreational drugs and engage in sexual activities, such as having multiple partners and insertive anal intercourse. Within individuals, average ED drug use was also positively correlated with sexual behaviors. [ABSTRACT FROM AUTHOR]

Background Neurocognitive impairment (NCI) and frailty are more prevalent among persons with human immunodeficiency virus (HIV, PWH) compared to those without HIV. Frailty and NCI often overlap with one another. Whether frailty precedes declines in neurocognitive function among PWH or vice versa has not been well established. Methods AIDS Clinical Trials Group (ACTG) A5322 is an observational cohort study of older PWH. Participants undergo annual assessments for NCI and frailty. ACTG A5322 participants who developed NCI as indexed by tests of impaired executive functioning and processing speed during the first 3 years were compared to persons who maintained normal cognitive function; those who demonstrated resolution of NCI were compared to those who had persistent NCI. Participants were similarly compared by frailty trajectory. We fit multinomial logistic regression models to assess associations between baseline covariates (including NCI) and frailty, and associations between baseline covariates (including frailty) and NCI. Results In total, 929 participants were included with a median age of 51 years (interquartile range [IQR] 46–56). At study entry, 16% had NCI, and 6% were frail. Over 3 years, 6% of participants developed NCI; 5% developed frailty. NCI was associated with development of frailty (odds ratio [OR] = 2.06; 95% confidence interval [CI] = .94, 4.48; P  = .07). Further adjustment for confounding strengthened this association (OR = 2.79; 95% CI = 1.21, 6.43; P  = .02). Baseline frailty however was not associated with NCI development. Conclusions NCI was associated with increased risk of frailty, but frailty was not associated with development of NCI. These findings suggest that the presence of NCI in PWH should prompt monitoring for the development of frailty and interventions to prevent frailty in this population. [ABSTRACT FROM AUTHOR]

Background: Sex hormone-binding globulin (SHBG) is a glycoprotein that regulates sex hormone bioavailability and increases with age in the general population. SHBG concentrations are higher in people with HIV, a population in whom accelerated aging has been hypothesized. It is unclear whether longitudinal changes in SHBG increase over time and differ by HIV serostatus. Methods: In a longitudinal study, SHBG was measured in 182 men with HIV (MWH) and 267 men without HIV (seronegative) from the Multicenter AIDS Cohort Study and matched for age, race, site, and time, with $2 SHBG serum samples over the 10 years after HAART initiation. Multivariable linear mixed-effects regression models were used to evaluate whether log-transformed SHBG [ln(SHBG)] and its rate of change differed by HIV serostatus. Results: At baseline, the mean age in MWH was similar to that in HIV-seronegative men (51 6 5 vs 49 6 6 years). However, SHBG mean values were higher in MWH compared with those in HIVseronegative men (65.6 6 48.8 vs. 45.4 6 22 nmol/L, P, 0.001). In a fully adjusted model, SHBG increased over time and at a faster rate in MWH compared with that in HIV-seronegative men: [2.0%/year (95% CI: 1.4 to 2.7) vs 1.3%/year (95% CI: 0.8 to 1.8), respectively, P = 0.038]. Among MWH, higher SHBG concentrations were significantly associated with lower CD4+ T-cell count [b= 20.02 (95% CI: 20.03 to 20.0002), P, 0.05], fewer cumulative years on zidovudine [b = 20.027 (95% CI: 20.045 to 20.009), P, 0.001], and greater cumulative years on nonnucleoside reverse transcriptase inhibitors drugs [b = 0.022 (95% CI: 0.0006 to 0.04), P, 0.05]. Conclusions: Aging-related increases in SHBG were faster in MWH compared with those in HIV-seronegative men and were related to poorer immunologic status and antiretroviral medication exposure. The mechanisms and consequences of these findings require further investigation. [ABSTRACT FROM AUTHOR]

Background Neurocognitive impairment (NCI) is associated with monocyte activation in people with HIV (PWH). Activated monocytes increase glycolysis, reduce oxidative phosphorylation, and accumulate citrate and succinate, tricarboxylic acid (TCA) cycle metabolites that promote inflammation—this metabolic shift may contribute to NCI and slowed gait speed in PWH. Methods Plasma citrate and succinate were assayed by liquid chromatography–mass spectrometry from 957 participants upon entry to a multicenter, prospective cohort of older PWH. Logistic, linear, and mixed-effects linear regression models were used to examine associations between entry/baseline TCA cycle metabolites and cross-sectional and longitudinal NCI, neuropsychological test scores (NPZ-4), and gait speed. Results Median age was 51 (range 40–78) years. Each 1 standard deviation (SD) citrate increment was associated with 1.18 higher odds of prevalent NCI at baseline (P =.03), 0.07 SD lower time-updated NPZ-4 score (P =.01), and 0.02 m/s slower time-updated gait speed (P <.0001). Age accentuated these effects. In the oldest age-quartile, higher citrate was associated with 1.64 higher odds of prevalent NCI, 0.17 SD lower NPZ-4, and 0.04 m/s slower gait speed (P ≤.01 for each). Similar associations were apparent with succinate in the oldest age-quintile, but not with gait speed. In participants without NCI at entry, higher citrate predicted a faster rate of neurocognitive decline. Conclusions Higher plasma citrate and succinate are associated with worse cross-sectional and longitudinal measures of neurocognitive function and gait speed that are age-dependent, supporting the importance of altered bioenergetic metabolism in the pathogenesis of NCI in older PWH. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background The prevalence and burden of age-related non-AIDS comorbidities (NACMs) are poorly characterized among women living with HIV (WLWH). Methods Virologically suppressed WLWH and HIV-seronegative participants followed in the Women's Interagency HIV Study (WIHS) through at least 2009 (when >80% of WLWH used antiretroviral therapy) were included, with outcomes measured through 31 March 2018. Covariates, NACM number, and prevalence were summarized at most recent WIHS visit. We used linear regression models to determine NACM burden by HIV serostatus and age. Results Among 3232 women (2309 WLWH, 923 HIV-seronegative) with median observation of 15.3 years, median age and body mass index (BMI) were 50 years and 30 kg/m2, respectively; 65% were black; 70% ever used cigarettes. WLWH had a higher mean NACM number than HIV-seronegative women (3.6 vs 3.0, P  < .0001) and higher prevalence of psychiatric illness, dyslipidemia, non-AIDS cancer, kidney, liver, and bone disease (all P  < .01). Prevalent hypertension, diabetes, and cardiovascular and lung disease did not differ by HIV serostatus. Estimated NACM burden was higher among WLWH versus HIV-seronegative women in those aged 40–49 (P  < .0001) and ≥60 years (P  = .0009) (HIV × age interaction, P  = .0978). In adjusted analyses, NACM burden was associated with HIV, age, race, income, BMI, alcohol abstinence, cigarette, and crack/cocaine use; in WLWH, additional HIV-specific indices were not associated, aside from recent abacavir use. Conclusions Overall, NACM burden was high in the cohort, but higher in WLWH and in certain age groups. Non-HIV traditional risk factors were significantly associated with NACM burden in WLWH and should be prioritized in clinical guidelines for screening and intervention to mitigate comorbidity burden in this high-risk population. [ABSTRACT FROM AUTHOR]

Background: The longer-term risks of statins on physical function among people with HIV are unclear. Methods: 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. Results: 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. Conclusions: 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. [ABSTRACT FROM AUTHOR]

Introduction: Reduced estimated glomerular filtration rate (eGFR) is associated with increased risk of cardiovascular disease among people living with HIV (PLWH). It is unclear whether eGFR equations incorporating cystatin C (CysC) measurements are more predictive of preclinical cardiovascular disease than those using only creatinine (Cr). Objectives: The study aimed to determine which of the 3 Chronic Kidney Disease Epidemiology (CKD-EPI) eGFR equations is most associated with carotid intima media thickness (CIMT) and coronary artery calcium (CAC) score. Methods: This cross-sectional analysis of pooled data from 3 large cohorts compared the associations between the 3 CKD-EPI eGFR equations (Cr, CysC, and Cr-CysC) with CIMT and CAC score using multivariable regression analysis. eGFR and CIMT were analyzed as continuous variables. CAC scores were analyzed as a binary variable (detectable calcification versus nondetectable) and as a log10 Agatston score in those with detectable CAC. Results: Thousand four hundred eighty-seven participants were included, and of these 910 (562 HIV+ and 348 HIV2) had CIMT measurements and 366 (296 HIV+ and 70 HIV2) had CAC measurements available. In HIV2 participants, GFR estimated by any CKD-EPI equation did not significantly correlate with CIMT or CAC scores. When PLWH were analyzed separately including HIV-specific factors, only GFR estimated using Cr- Cys C correlated with CIMT [b= 20.90, 95% CI: (21.67 to 20.13) mm; P = 0.023]. Similarly, eGFR correlated with Agatston scores only when using cystatin C-based eGFR [b= 28.63, 95% CI: (216.49 to 20.77) HU; P = 0.034]. Associations between other eGFR formulas and CAC did not reach statistical significance. Conclusions: In PLWH, preclinical atherosclerosis may be more closely correlated with eGFR using formulae that incorporate CysC measurements than Cr alone. [ABSTRACT FROM AUTHOR]

Background Treatment initiation with integrase strand transfer inhibitors (INSTIs) has been associated with excess weight gain. Whether similar gains are seen after switch to INSTIs among virologically suppressed persons is less clear. We assessed pre/post-INSTI weight changes from AIDS Clinical Trials Group participants (A5001 and A5322). Methods Participants who were in follow-up from 1997–2017 and switched to INSTI-based antiretroviral regimens were included. Piecewise linear mixed-effects models adjusting for age, sex, race/ethnicity, baseline BMI, nadir and current CD4+ T-cell count, smoking, diabetes and follow-up time with suppressed HIV-1 RNA examined weight and waist circumference change before and after first switch to INSTIs. Linear spline models with a single knot at time of switch accounted for nonlinear trends. Results The 972 participants who switched to INSTIs were 81% male and 50% nonwhite with a median age at switch of 50 years, CD4+ T-cell count 512 cells/μL, and BMI 26.4 kg/m2. Restricting to persons with suppressed HIV-1 RNA at switch (n = 691), women, blacks, and persons ≥60 years experienced greater weight gain in the 2 years after versus before switch. In adjusted models, white or black race, age ≥60, and BMI ≥30 kg/m2 at switch were associated with greater weight gain following switch among women; age ≥60 was the greatest risk factor among men. Trends for waist circumference were similar. Conclusions Yearly weight gain increased following switch to INSTIs, particularly for women, blacks, and persons aged ≥60. Concomitant increases in waist circumference suggest that this weight gain is associated with an increase in fat mass. [ABSTRACT FROM AUTHOR]

Background: Suicidal ideation (SI) refers to an individual thinking about, considering or planning suicide. Identifying and characterizing persons with HIV (PWH) at greater risk for SI may lead to better suicide prevention strategies and quality of life improvement.Methods: Using clinical data gathered from medical chart abstraction for HIV Outpatient Study (HOPS) participants from 2000 to 2017, we assessed SI frequency among PWH in care and explored factors associated with the presence of SI diagnoses using linear mixed models analyses.Results: Among 6706 participants, 224 (3.3%) had a charted diagnosis of SI. Among those with SI, median age (interquartile range [IQR]) was 43.4 years [IQR: 38.7-50.3], median (IQR) CD4+ cell count was 439 cells/mm3 (IQR: 237-686), 71.4% were male, 54% were men who have sex with men (MSM), 25.4% heterosexual, and 13.4% persons who inject drugs. In multivariable analysis, persons at increased risk for SI were more likely to be: <50 years old (adjusted rate ratio [aRR] 1.86, 95% confidence interval [95%CI] 1.36-2.53), non-Hispanic/Latino black (aRR 1.75; 95%CI 1.29-2.38), have CD4+ cell count <350 cells/mm3 (aRR 1.32; 95%CI 1.05-1.65), have a viral load ≥50 copies/mL (aRR 1.49; 95%CI 1.12-1.98), have stopped antiretroviral therapy (aRR 1.46; 95%CI 1.10-1.95), have a history of: alcohol dependence (aRR 2.75; 95%CI 1.67-4.52), and drug overdose (aRR 4.09; 95%CI 2.16-7.71).Conclusion: Routine mental health assessment and monitoring are needed in HIV clinical practice to better understand factors associated with SI and to inform the development of preventive interventions. [ABSTRACT FROM AUTHOR]

Background The objective of this study was to investigate whether 100% antiretroviral therapy (ART) adherence in men with HIV (MWH) is associated with normalization of concentrations of biomarkers of inflammation and immune activation compared with HIV-uninfected men. Methods We analyzed person-visits with available biomarker data from the Multicenter AIDS Cohort Study (MACS) among MWH receiving ART with HIV RNA <50 copies/mL and among HIV-uninfected men. Self-reported adherence was classified as 100% if no missed ART doses in the past 4 days were reported. We evaluated associations between ART adherence and concentrations of 24 serum biomarkers compared with HIV-uninfected visits using a generalized gamma model, adjusting for potential confounders. Results Person-visits (2565 from MWH reporting 100% ART adherence and 1588 from HIV-uninfected men) from a total of 1469 men were included in the analysis. Serum concentrations of interleukin-6 (IL-6), soluble interleukin-6 receptor (sIL-6R), IL-1β, interferon-γ (IFN-γ), chemokine C-C motif ligand 2 (CCL2), and CCL14 from person-visits among MWH who reported 100% adherence were similar to HIV-uninfected person-visits. Comparatively higher concentrations of 11 biomarkers and lower concentrations of 7 biomarkers were observed in person-visits from MWH who reported 100% ART adherence, compared with HIV-uninfected person-visits. Conclusions Although MWH with virologic suppression who reported 100% ART adherence exhibited overall higher concentrations of biomarkers of inflammation and immune activation compared with HIV-uninfected men, some biomarker concentrations were similar in both groups. These findings suggest that optimal ART adherence could have clinical implications beyond achieving and sustaining viral suppression. [ABSTRACT FROM AUTHOR]

Background: Persons with HIV may experience greater mobility limitations than uninfected populations. Accurate tools are needed to identify persons at greatest risk of decline. We evaluated the performance of novel muscle weakness metrics (grip, grip/body mass index [BMI], grip/weight, grip/total body fat, grip/arm lean mass) and association with slowness and falls in older persons with or at risk for HIV infection as part of the work of the Sarcopenia Definitions and Outcomes Consortium (SDOC).Methods: We assessed the prevalence of sarcopenia among 398 men (200 HIV+, 198 HIV-) from the Multicenter AIDS Cohort Study and 247 women (162 HIV+, 85 HIV-) from the Women's Interagency HIV Study using previously validated muscle weakness metrics discriminative of slowness. Sensitivity and specificity were used to compare new muscle weakness and slowness criteria to previously proposed sarcopenia definitions.Results: The prevalence of muscle weakness ranged from 16% to 66% among men and 0% to 47% among women. Grip/BMI was associated with slowness among men with HIV only. Grip/BMI had low sensitivity (25%-30%) with moderate to high specificity (68%-89%) for discriminating of slowness; all proposed metrics had poor performance in the discrimination of slowness (area under the curve [AUC] < 0.62) or fall status (AUC < 0.56). The combination of muscle weakness and slowness was not significantly associated with falls (p ≥ .36), with a low sensitivity in identifying those sustaining one or more falls (sensitivity ≤ 16%).Discussion: Clinical utility of new sarcopenia metrics for identification of slowness or falls in men and women with or at risk for HIV is limited, given their low sensitivity. [ABSTRACT FROM AUTHOR]

Introduction: Weight gain following antiretroviral therapy (ART) initiation is common, potentially predisposing some persons with HIV (PWH) to cardio‐metabolic disease. We assessed relationships between ART drug class and weight change among treatment‐naïve PWH initiating ART in the North American AIDS Cohort Collaboration on Research and Design (NA‐ACCORD). Methods: Adult, treatment‐naïve PWH in NA‐ACCORD initiating integrase strand transfer inhibitor (INSTI), protease inhibitor (PI) or non‐nucleoside reverse‐transcriptase inhibitor (NNRTI)‐based ART on/after 1 January 2007 were followed through 31 December 2016. Multivariate linear mixed effects models estimated weight up to five years after ART initiation, adjusting for age, sex, race, cohort site, HIV acquisition mode, treatment year, and baseline weight, plasma HIV‐1 RNA level and CD4+ cell count. Due to shorter follow‐up for PWH receiving newer INSTI drugs, weights for specific INSTIs were estimated at two years. Secondary analyses using logistic regression and all covariates from primary analyses assessed factors associated with >10% weight gain at two and five years. Results: Among 22,972 participants, 87% were male, and 41% were white. 49% started NNRTI‐, 31% started PI‐ and 20% started INSTI‐based regimens (1624 raltegravir (RAL), 2085 elvitegravir (EVG) and 929 dolutegravir (DTG)). PWH starting INSTI‐based regimens had mean estimated five‐year weight change of +5.9kg, compared to +3.7kg for NNRTI and +5.5kg for PI. Among PWH starting INSTI drugs, mean estimated two‐year weight change was +7.2kg for DTG, +5.8kg for RAL and +4.1kg for EVG. Women, persons with lower baseline CD4+ cell counts, and those initiating INSTI‐based regimens had higher odds of >10% body weight increase at two years (adjusted odds ratio = 1.37, 95% confidence interval: 1.20 to 1.56 vs. NNRTI). Conclusions: PWH initiating INSTI‐based regimens gained, on average, more weight compared to NNRTI‐based regimens. This phenomenon may reflect heterogeneous effects of ART agents on body weight regulation that require further exploration. [ABSTRACT FROM AUTHOR]

Improvements in life expectancy among people living with human immunodeficiency virus (PLWH) receiving antiretroviral treatment in the United States and Canada might differ among key populations. Given the difference in substance use among key populations and the current opioid epidemic, drug- and alcohol-related deaths might be contributing to the disparities in life expectancy. We sought to estimate life expectancy at age 20 years in key populations (and their comparison groups) in 3 time periods (2004–2007, 2008–2011, and 2012–2015) and the potential increase in expected life expectancy with a simulated 20% reduction in drug- and alcohol-related deaths using the novel Lives Saved Simulation model. Among 92,289 PLWH, life expectancy increased in all key populations and comparison groups from 2004–2007 to 2012–2015. Disparities in survival of approximately a decade persisted among black versus white men who have sex with men and people with (vs. without) a history of injection drug use. A 20% reduction in drug- and alcohol-related mortality would have the greatest life-expectancy benefit for black men who have sex with men, white women, and people with a history of injection drug use. Our findings suggest that preventing drug- and alcohol-related deaths among PLWH could narrow disparities in life expectancy among some key populations, but other causes of death must be addressed to further narrow the disparities. [ABSTRACT FROM AUTHOR]

Background We characterized associations between frailty and incident cardiovascular disease (CVD), diabetes mellitus (DM), bone disease, and mortality within a cohort of aging persons with human immunodeficiency virus (PWH). Methods Participants underwent frailty evaluations using the Fried frailty assessment (baseline and annually). Frailty was defined as having ≥3 frailty criteria. Clinical outcomes of mortality, CVD events, DM, and bone disease events were recorded throughout the study period (baseline to most recent study or clinic visit, or date of clinical outcome, whichever came first). Poisson regression models were used to evaluate associations between baseline frailty, change in frailty score over 48 weeks, and each clinical outcome. Results Among 821 men and 195 women (median age 51 years), 62 (6%) were frail at baseline. Frailty scores increased by ≥1 component among 194 participants (19%) from baseline to 48 weeks. Baseline frailty was associated with an increased risk of incident CVD and DM, with a trend toward a significant association with bone events. Among frailty components, slow gait speed was associated with incident DM and borderline associated with incident CVD. An increase in frailty from baseline to week 48 was associated with mortality but not with the other clinical outcomes. Conclusions Baseline frailty was associated with multiple adverse health outcomes (incident CVD, DM, and bone disease), while increase in frailty score was associated with mortality among PWH engaged in care. Incorporation of frailty assessments into the care of PWH may assist in improvement of functional status and risk stratification for age-related chronic diseases. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) occurs commonly among HIV-infected persons. Statins may delay CKD onset and progression through their cholesterol-lowering and pleiotropic effects. Methods: Among 850 HIV-infected men from the Multicenter AIDS Cohort Study with stored urine samples (2009-2011), we evaluated cross-sectional associations of statin use with urine biomarkers of kidney damage [albumin-to-creatinine ratio (ACR), alpha-1-microglobulin, interleukin-18, kidney injury molecule-1, and procollagen type III N-terminal propeptide] using multivariable linear regression. We evaluated the longitudinal associations of statin use with annual change in estimated glomerular filtration rate by creatinine (eGFR) using linear mixed models, and with incident proteinuria and incident CKD (eGFR <60 mL/min/1.73 m2) using Cox proportional hazards regression. We used inverse probability weighting to address potential confounding related to statin use. Results: Statin users comprised 30% of participants. In adjusted analyses, each year of cumulative statin use was associated with 4.0% higher baseline ACR levels (P = 0.05), but there was no association with baseline levels of other urine biomarkers. Statin use had no overall association with annual eGFR decline. Among participants with baseline proteinuria, statin use was modestly associated with slower annual eGFR decline compared to non-use (adjusted difference: 1.33 mL/min/1.73 m2 per year; 95% confidence interval: -0.07 to 2.70). Statin use was not associated with risk of incident proteinuria or incident CKD. Conclusions: Statin use was associated with higher baseline ACR, but not with biomarkers of tubulointerstitial injury. Statin use was associated with modestly slower eGFR decline only among participants with baseline proteinuria. Although these findings may be susceptible to confounding by indication, they suggest a limited effect of statins on CKD risk among HIV-infected men. [ABSTRACT FROM AUTHOR]

Background: Falls and fall risk factors are common among people living with HIV (PLWH). We sought to identify fall risk factors among men with and without HIV. Methods: Men aged 50–75 years with (n = 279) and without HIV (n = 379) from the Bone Strength Substudy of the Multicenter AIDS Cohort Study were included. Multinomial logistic regression models identified risk factors associated with falling. Results: One hundred fourteen (41%) PLWH and 149 (39%) of uninfected men had ≥1 fall; 54 (20%) PLWH and 66 (17%) of uninfected men experienced ≥2 falls over 2 years. Five and 3% of PLWH and uninfected men, respectively, had a fall-related fracture (P = 0.34). In multivariate models, the odds of ≥2 falls were greater among men reporting illicit drug use, taking diabetes or depression medications, and with peripheral neuropathy; obesity was associated with a lower risk (all P < 0.05). In models restricted to PLWH, detectable plasma HIV-1 RNA, current use of efavirenz or diabetes medications, illicit drug use, and peripheral neuropathy were associated with greater odds of having ≥2 falls (P < 0.05). Current efavirenz use was associated with increased odds of an injurious fall; longer duration of antiretroviral therapy was protective (both P < 0.05). Greater physical activity was associated with lower risk of falls with fracture (P < 0.05). Conclusions: Identified risk factors for recurrent falls or fall with fracture included low physical activity, detectable HIV-1 RNA, use of efavirenz, or use of medications to treat diabetes and depression. Fall risk reduction should prioritize interventions targeting modifiable risk factors including increased physical activity, antiretroviral therapy adherence, and transition off efavirenz. [ABSTRACT FROM AUTHOR]