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BackgroundSevere 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.SettingLongitudinal survey within the MACS/WIHS Combined Cohort Study (MWCCS) of PLWH compared with similar HIV-seronegative (SN) individuals.MethodsTelephone-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).ResultsOne-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).ConclusionsDespite 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.

BackgroundChronic kidney disease (CKD) occurs commonly among HIV-infected persons. Statins may delay CKD onset and progression through their cholesterol-lowering and pleiotropic effects.MethodsAmong 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

BACKGROUND:Proteinuria has been associated with bone loss and fractures in general population, but data in HIV-infected population are lacking. SETTING:Prospective, multicenter cohort study of men with or at risk of HIV infection. METHODS:Between 2006 and 2015, urine protein measurements and bone fracture histories were ascertained semiannually in 947 HIV-infected (HIV+) and 969 HIV-uninfected (HIV-) men aged 40 years or older. Proteinuria was defined as protein-to-creatinine ratio ≥200 mg/g at ≥2 consecutive visits. Outcome measures (1) all fractures (excluding fractures of skull, face, and digits) and (2) fragility fractures (fractures of vertebral column, femur, wrist, and humerus). Multivariable Cox proportional hazards models assessed the association between proteinuria and fracture after adjusting for additional risk factors. RESULTS:The overall period prevalence of proteinuria was higher among HIV+ than HIV- (29% vs 6%, P < 0.001). Men with proteinuria had a significantly higher risk of fragility fracture compared with men without proteinuria [adjusted hazard ratio (aHR) = 2.29 (1.12-4.66)] and did not differ by HIV serostatus (p-interaction = 0.83). The risk of all fractures was not statistically different between men with or without proteinuria [aHR = 1.31 (0.84-2.05)]. Among HIV+ men, the association between confirmed proteinuria and fragility fracture was attenuated [aHR = 2.12 (0.95-4.73)] after additional adjustment for CD4 T-cell count/mm, history of AIDS, the presence of detectable plasma HIV-1 RNA, and cumulative exposure to tenofovir disoproxil fumarate. CONCLUSIONS:Proteinuria was more common in HIV+ than in HIV- men and was a strong independent risk factor for fragility fracture regardless of HIV serostatus. Proteinuria should prompt consideration of a thorough evaluation for bone disease among HIV+ persons.

BackgroundIn the Multicenter AIDS Cohort Study, we examined whether fibroblast growth factor-23 (FGF-23), a bone-derived phosphaturic hormone involved in bone metabolism, is associated with incident frailty. Furthermore, we examined whether this association differs by HIV serostatus and race.MethodsOf 715 men assessed for frailty and selected for FGF-23 measurements using stored blood samples (2007-2011), 512 men were nonfrail at/before the baseline visit. Frailty was defined by the presence of ≥3 of the following on 2 consecutive 6-month visits within 1 year: unintentional weight loss ≥10 pounds, weakness, slowness, low energy, and low physical activity. We determined the association of FGF-23 levels with incident frailty using proportional hazards models adjusting for sociodemographics, comorbidities, and kidney function.ResultsSixty-five percent were HIV-infected; 29% were black. Median baseline FGF-23 levels were lower in HIV-infected vs. HIV-uninfected men (33.7 vs. 39.9 rU/mL, P = 0.006) but similar by race. During a median follow-up of 6.6 years, 32 men developed frailty; they had higher baseline FGF-23 levels vs. men who remained nonfrail (45 vs. 36 rU/mL, P = 0.02). FGF-23 (per doubling) was associated with a 1.63-fold risk of frailty [95% confidence interval (CI): 1.19 to 2.23]; results did not differ by HIV serostatus. Conversely, FGF-23 was associated with a 2.72-fold risk of frailty among blacks (95% CI: 1.51 to 4.91) but had minimal association among nonblacks (hazard ratio = 1.26, 95% CI: 0.77 to 2.05; p-interaction = 0.024).ConclusionsAmong men with or at-risk of HIV infection, higher FGF-23 was associated with greater risk of frailty, particularly in blacks. The mechanisms by which FGF-23 may contribute to frailty warrant further study.

BackgroundThere is persistent confusion as to whether abacavir (ABC) increases the risk of myocardial infarction (MI), and whether such risk differs by type 1 (T1MI) or 2 (T2MI) MI in adults with HIV.MethodsIncident MIs in North American Cohort Collaboration on Research and Design participants were identified from 2001 to 2013. Discrete time marginal structural models addressed channeling biases and time-dependent confounding to estimate crude hazard ratio (HR) and adjusted hazard ratio (aHR) and 95% confidence intervals; analyses were performed for T1MI and T2MI separately. A sensitivity analysis evaluated whether Framingham risk score (FRS) modified the effect of ABC on MI occurrence.ResultsEight thousand two hundred sixty-five adults who initiated antiretroviral therapy contributed 29,077 person-years and 123 MI events (65 T1MI and 58 T2MI). Median follow-up time was 2.9 (interquartile range 1.4-5.1) years. ABC initiators were more likely to have a history of injection drug use, hepatitis C virus infection, hypertension, diabetes, impaired kidney function, hyperlipidemia, low (

BackgroundPrevious studies of cardiovascular disease (CVD) among HIV-infected individuals have been limited by the inability to validate and differentiate atherosclerotic type 1 myocardial infarctions (T1MIs) from other events. We sought to define the incidence of T1MIs and risk attributable to traditional and HIV-specific factors among participants in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) and compare adjusted incidence rates (IRs) to the general population Atherosclerosis Risk in Communities (ARIC) cohort.MethodsWe ascertained and adjudicated incident MIs among individuals enrolled in 7 NA-ACCORD cohorts between 1995 and 2014. We calculated IRs, adjusted incidence rate ratios (aIRRs), and 95% confidence intervals of risk factors for T1MI using Poisson regression. We compared aIRRs of T1MIs in NA-ACCORD with those from ARIC.ResultsAmong 29,169 HIV-infected individuals, the IR for T1MIs was 2.57 (2.30 to 2.86) per 1000 person-years, and the aIRR was significantly higher compared with participants in ARIC [1.30 (1.09 to 1.56)]. In multivariable analysis restricted to HIV-infected individuals and including traditional CVD risk factors, the rate of T1MI increased with decreasing CD4 count [≥500 cells/μL: ref; 350-499 cells/μL: aIRR = 1.32 (0.98 to 1.77); 200-349 cells/μL: aIRR = 1.37 (1.01 to 1.86); 100-199 cells/μL: aIRR = 1.60 (1.09 to 2.34);

Tenofovir disoproxil fumarate (TDF) can cause kidney damage, but current clinical tests are insensitive for detecting toxicity. Among 884 HIV-infected men enrolled in the Multicenter AIDS Cohort Study, we measured urine biomarkers specific for tubular damage (interleukin-18, kidney injury molecule-1, procollagen type III N-terminal propeptide) and albuminuria. In adjusted analyses, each year of TDF exposure was independently associated with 3.3% higher interleukin-18 (95% CI: 0.8% to 5.8%), 3.4% higher kidney injury molecule-1 (1.1% to 5.7%), and 3.1% higher procollagen type III N-terminal propeptide (0.8% to 5.5%), but not with albuminuria (2.8%; -0.6% to 6.2%). Biomarkers of tubular damage may be more sensitive than albuminuria for detecting toxicity from TDF and other medications.

Recent evidence has shown a complex relationship between the gut microbiota, dietary nutrients, and cardiovascular disease (CVD). Trimethylamine-N-oxide (TMAO) production, initiated by the microbiota, has been associated with CVD events. We sought to test if this association exists in HIV-infected persons. After adjusting for aspirin use and CVD risk factors, HIV-infected men were more likely to have coronary stenosis in the second and third TMAO quartiles compared with the first quartile, but did not differ significantly in the fourth quartile. We found an inverted U-shaped association between TMAO levels and the presence of coronary artery stenosis among HIV-infected men.

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.