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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]

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]

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]

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]

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]

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]

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 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]

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]

Objective: HIV-infected (HIV+) individuals may be at increased risk for sudden arrhythmic cardiac death. Some studies have reported an association between HIV infection and prolongation of the electrocardiographic QT interval, a measure of ventricular repolarisation, which could potentiate ventricular arrhythmias. We aimed to assess whether HIV+ men have longer QT intervals than HIV-uninfected (HIV-) men and to determine factors associated with QT duration.Methods: We performed resting 12-lead ECGs in 774 HIV+ and 652 HIV- men in the Multicenter AIDS Cohort Study (MACS). We used multivariable linear and logistic regression analyses to assess associations between HIV serostatus and Framingham corrected QT interval (QTc), after accounting for potential confounders. We also determined associations among QTc interval and HIV-related factors in HIV+ men. In a subgroup of participants, levels of serum markers of inflammation were also assessed.Results: After adjusting for demographics and risk factors, QTc was 4.0 ms longer in HIV+ than HIV- men (p<0.001). Use of antiretroviral therapy (ART), specific ART drug class use and other HIV-specific risk factors were not associated with longer QTc. Among the subgroup with inflammatory biomarker measurements, higher interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1) and B-cell activating factor levels were independently associated with longer QTc and their inclusion partially attenuated the HIV effect.Conclusions: HIV+ men had longer QTc, which was associated with higher levels of systemic inflammatory factors. This longer QTc may contribute to the increased risk for sudden arrhythmic cardiac death in some HIV+ individuals. [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]

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]

Objective: Marijuana, tobacco and alcohol use are prevalent among people with HIV and may adversely affect kidney function in this population. We determined the association of use of these substances with estimated glomerular filtration rate (eGFR) among women with HIV (WWH) and women without HIV., Design: We undertook a repeated measures study of 1043 WWH and 469 women without HIV within the United States Women's Interagency HIV Study, a multicenter, prospective cohort of HIV-seropositive and HIV-seronegative women., Methods: We quantified substance exposures using semi-annual questionnaires. Using pooled eGFR data from 2009 to 2019, we used linear regression models with multivariable generalized estimating equations to ascertain associations between current and cumulative substance use exposures with eGFR, adjusting for sociodemographics, chronic kidney disease risk factors and HIV-related factors., Results: Marijuana use of 1-14 days/month versus 0 days/month was associated with 3.34 ml/min per 1.73 m 2 [95% confidence interval (CI) -6.63, -0.06] lower eGFR and marijuana use of >0.02-1.6 marijuana-years versus 0-0.2 marijuana-years was associated with 3.61 ml/min per 1.73 m 2 (95% CI -5.97, -1.24) lower eGFR. Tobacco use was not independently associated with eGFR. Alcohol use of seven or more drinks/week versus no drinks/week was associated with 5.41 ml/min per 1.73 m 2 (95% CI 2.34, 8.48) higher eGFR and alcohol use of >0.7-4.27 drink-years and >4.27 drink-years versus 0-0.7 drink-years were associated with 2.85 ml/min per 1.73 m 2 (95% CI 0.55, 5.15) and 2.26 ml/min per 1.73 m 2 (95% CI 0.33, 4.20) higher eGFR, respectively., Conclusion: Among a large cohort of WWH and women without HIV, marijuana use was associated with a lower eGFR while alcohol use was associated with a higher eGFR., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Importance: Despite aging-related comorbidities representing a growing threat to quality-of-life and mortality among persons with HIV (PWH), clinical guidance for comorbidity screening and prevention is lacking. Understanding comorbidity distribution and severity by sex and gender is essential to informing guidelines for promoting healthy aging in adults with HIV., Objective: To assess the association of human immunodeficiency virus on the burden of aging-related comorbidities among US adults in the modern treatment era., Design, Setting, and Participants: This cross-sectional analysis included data from US multisite observational cohort studies of women (Women's Interagency HIV Study) and men (Multicenter AIDS Cohort Study) with HIV and sociodemographically comparable HIV-seronegative individuals. Participants were prospectively followed from 2008 for men and 2009 for women (when more than 80% of participants with HIV reported antiretroviral therapy use) through last observation up until March 2019, at which point outcomes were assessed. Data were analyzed from July 2020 to April 2021., Exposures: HIV, age, sex., Main Outcomes and Measures: Comorbidity burden (the number of total comorbidities out of 10 assessed) per participant; secondary outcomes included individual comorbidity prevalence. Linear regression assessed the association of HIV status, age, and sex with comorbidity burden., Results: A total of 5929 individuals were included (median [IQR] age, 54 [46-61] years; 3238 women [55%]; 2787 Black [47%], 1153 Hispanic or other [19%], 1989 White [34%]). Overall, unadjusted mean comorbidity burden was higher among women vs men (3.4 [2.1] vs 3.2 [1.8]; P = .02). Comorbidity prevalence differed by sex for hypertension (2188 of 3238 women [68%] vs 2026 of 2691 men [75%]), psychiatric illness (1771 women [55%] vs 1565 men [58%]), dyslipidemia (1312 women [41%] vs 1728 men [64%]), liver (1093 women [34%] vs 1032 men [38%]), bone disease (1364 women [42%] vs 512 men [19%]), lung disease (1245 women [38%] vs 259 men [10%]), diabetes (763 women [24%] vs 470 men [17%]), cardiovascular (493 women [15%] vs 407 men [15%]), kidney (444 women [14%] vs 404 men [15%]) disease, and cancer (219 women [7%] vs 321 men [12%]). In an unadjusted model, the estimated mean difference in comorbidity burden among women vs men was significantly greater in every age strata among PWH: age under 40 years, 0.33 (95% CI, 0.03-0.63); ages 40 to 49 years, 0.37 (95% CI, 0.12-0.61); ages 50 to 59 years, 0.38 (95% CI, 0.20-0.56); ages 60 to 69 years, 0.66 (95% CI, 0.42-0.90); ages 70 years and older, 0.62 (95% CI, 0.07-1.17). However, the difference between sexes varied by age strata among persons without HIV: age under 40 years, 0.52 (95% CI, 0.13 to 0.92); ages 40 to 49 years, -0.07 (95% CI, -0.45 to 0.31); ages 50 to 59 years, 0.88 (95% CI, 0.62 to 1.14); ages 60 to 69 years, 1.39 (95% CI, 1.06 to 1.72); ages 70 years and older, 0.33 (95% CI, -0.53 to 1.19) (P for interaction = .001). In the covariate-adjusted model, findings were slightly attenuated but retained statistical significance., Conclusions and Relevance: In this cross-sectional study, the overall burden of aging-related comorbidities was higher in women vs men, particularly among PWH, and the distribution of comorbidity prevalence differed by sex. Comorbidity screening and prevention strategies tailored by HIV serostatus and sex or gender may be needed.

Attention to non-AIDS comorbidities is increasingly important in the HIV care and management in the United States. We sought to assess comorbidities before and after antiretroviral therapy (ART) initiation among persons with HIV (PWH). Using the 2008-2018 HIV Outpatient Study (HOPS) data, we assessed changes in prevalence of physical and psychiatric comorbidities, by sex, among participants initiating ART. Cox proportional hazards models were fit to investigate factors associated with the first documented occurrence of key comorbidities, adjusting for demographics and other covariates, including insurance type, CD4 + cell count, ART regimen, and smoking status. Among 1,236 participants who initiated ART (median age 36 years, CD4 cell count 375 cells/mm 3 ), 79% were male, 66% non-white, 44% publicly insured, 53% ever smoked, 33% had substance use history, and 22% had body mass index ≥30 kg/m 2 . Among females, the percentages with at least one condition were: at ART start, 72% had a physical and 42% a psychiatric comorbidity, and after a median of 6.1 years of follow-up, these were 87% and 63%, respectively. Among males, the percentages with at least one condition were: at ART start, 61% had a physical and 32% a psychiatric comorbidity, and after a median of 4.6 years of follow-up, these were 82% and 53%, respectively. In multivariable Cox proportional hazards analyses, increasing age and higher viral loads (VL) were associated with most physical comorbidities, and being a current/former smoker and higher VL were associated with all psychiatric comorbidities analyzed. HOPS participants already had a substantial burden of physical and psychiatric comorbidities at the time of ART initiation. With advancing age, PWH who initiate ART experience a clinically significant increase in the burden of chronic non-HIV comorbidities that warrants continued surveillance, prevention, and treatment.

Objective: To determine the longitudinal relationships between abnormal glucose metabolism and physical function in persons with HIV (PWH) and without HIV., Design: Prospective cohort study of men with or at risk for HIV in four United States cities between 2006 and 2018., Methods: Men with or at risk for HIV from the Multicenter AIDS Cohort Study (MACS) had semi-annual assessments of glycemic status, grip strength, and gait speed. We used linear mixed models with random intercept to assess associations between glycemic status and physical function. Glycemic status was categorized as normal, impaired fasting glucose (IFG), controlled diabetes mellitus [hemoglobin A1C (HbA1C) <7.5%], or uncontrolled diabetes mellitus (HbA1C ≥ 7.5%)., Results: Of 2240 men, 52% were PWH. Diabetes mellitus was similar among PWH (7.7%) vs. persons without HIV (6.7%, P = 0.36) at baseline. PWH had slower gait speed (1.17 vs. 1.20 m/s, P < 0.01) but similar grip strength (40.1 vs. 39.8 kg, P = 0.76) compared with persons without HIV at baseline. In multivariate models, gait speed decline was greater with controlled diabetes mellitus [-0.018 m/s (-0.032 to -0.005), P = 0.01] and grip strength decline was greater with controlled [-0.560 kg (-1.096 to -0.024), P = 0.04] and uncontrolled diabetes mellitus [-0.937 kg (-1.684 to -0.190), P = 0.01), regardless of HIV serostatus compared with normoglycemic individuals., Discussion: Abnormal glucose metabolism was associated with declines in gait speed and grip strength regardless of HIV serostatus. These data suggest that improvement in glucose control should be investigated as an intervenable target to prevent progression of physical function limitations among PWH., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: The aim of this study was to identify viral exposure (VE) measures and their relationship to mortality risk among persons with HIV.Prospective multicenter observational study to compare VE formulae.Eligible participants initiated first combination antiretroviral therapy (cART) between March 1, 1995 and June 30, 2015. We included 1645 participants followed for ≥6 months after starting first cART, with cART prescribed ≥75% of time, who underwent ≥2 plasma viral load (VL) and ≥1 CD4+ T-lymphocyte cell (CD4) measurement during observation. We evaluated all-cause mortality from 6 months after cART initiation until June 30, 2016. VE was quantified using 2 time-updated variables: viremia copy-years and percent of person-years (%PY) spent >200 or 50 copies/mL. Cox models were fit to estimate associations between VE and mortality.Participants contributed 10,453 person years [py], with median 14 VLs per patient. Median %PY >200 or >50 were 10% (interquartile range: 1%-47%) and 26% (interquartile range: 6%-72%), respectively. There were 115 deaths, for an overall mortality rate of 1.19 per 100 person years. In univariate models, each measure of VE was significantly associated with mortality risk, as were older age, public insurance, injection drug use HIV risk history, and lower pre-cART CD4. Based on model fit, most recent viral load and %PY >200 copies/mL provided the best combination of VE factors to predict mortality, although all VE combinations evaluated performed well.The combination of most recent VL and %PY >200 copies/mL best predicted mortality, although all evaluated VE measures performed well., Competing Interests: Conflicts of interest: FJP has been a consultant and/or on the Speakers’ Bureau for Gilead Sciences, Janssen Pharmaceuticals, Merck and Co. and ViiV. The authors report no conflicts of interest., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: SARS-CoV-2 infection among People Living With HIV (PLWH) is not well-described., Objective: To study COVID-19 symptoms and SARS-CoV-2 PCR-based swab testing among participants of the Multicenter AIDS Cohort Study (MACS) and Women's Interagency HIV Study (WIHS)., Methods: A telephone survey was collected April-June 30, 2020. Symptom and testing prevalence were explored. Multivariable logistic regression was used to examine the factors associated with SARS-CoV-2 positivity., Results: The survey was completed by 3411 participants, including 2078 (61%) PLWH and 1333 HIV-seronegative (SN) participants from across the US. Thirteen percent (n = 441) were tested for SARS-CoV-2 infection (13.4% of PLWH vs 12.2% of SN). Among those tested, positivity was higher in PLWH than SN (11.2% vs 6.1%, p  = 0.08). Reasons for not being tested included testing not being available (30% of participants) and not knowing where to get tested (16% of participants). Most symptoms reported since January 2020 were similar in PLWH and SN, including headache (23% vs. 24%), myalgias (19% vs 18%), shortness of breath (14% vs 13%), chills (12% vs 10%), fever (6% vs 6%) and loss of taste or smell (6% vs 7%). Among PLWH who tested positive for SARS-CoV-2 DNA, the most common symptoms were headache (71%), myalgia (68%), cough (68%) and chills (65%). In multivariable analysis among those tested, the odds of SARS-CoV-2 positivity were higher among PLWH than SN (aOR = 2.22 95%CI = 01.01-4.85, p  = 0.046) and among those living with others versus living alone (aOR = 2.95 95%CI = 1.18-7.40)., Conclusion: Prevalence and type of COVID-19 symptoms were similar in PLWH and SN. SARS-CoV-2 infection may be elevated among PLWH.

Objectives: The purpose of this study was to compare the risks of incident heart failure (HF) among a variety of chronic inflammatory diseases (CIDs) and to determine whether risks varied by severity of inflammation within each CID., Background: Individuals with CIDs are at elevated risk for cardiovascular diseases, but data are limited regarding risk for HF., Methods: An electronic health records database from a large urban medical system was examined, comparing individuals with CIDs with frequency-matched controls without CIDs, all of whom were receiving regular outpatient care. Rates of incident HF were determined by using the Kaplan-Meier method and subsequently used multivariate-adjusted proportional hazards models to compare HF risks for each CID. Exploratory analyses determined HF risks by proxy measurement of CID severity., Results: Of 37,636 patients (n = 18,278 patients with CIDs; and n = 19,358 controls without CIDs) there were 960 incident HF cases over a median of 3.6 years. Risks for incident HF were significantly or borderline significantly elevated for patients with systemic sclerosis (hazard ratio [HR]: 7.26; 95% confidence interval [CI]: 5.72 to 9.21; p < 0.01), systemic lupus erythematosus (HR: 3.15; 95% CI: 2.41 to 4.11; p < 0.01), rheumatoid arthritis (HR: 1.39; 95% CI: 1.13 to 1.71; p < 0.01), and human immunodeficiency virus (HR: 1.28; 95% CI: 0.99 to 1.66; p = 0.06). There was no association between psoriasis or inflammatory bowel disease and incident HF, although patients with those CIDs with higher levels of C-reactive protein had higher risks for HF than controls., Conclusions: Systemic sclerosis and systemic lupus erythematosus were associated with the highest risks of HF, followed by rheumatoid arthritis and HIV. Measurements of inflammation were associated with HF risk across different CIDs., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

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/mm 3 (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/mm 3 (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., Competing Interests: Declaration of competing interest The authors do not have any associations that may pose a conflict of interest., (Published by Elsevier Inc.)

Background: The purpose of this study is to determine if a new score calculated with coronary artery calcium (CAC) density and volume is associated with total coronary artery plaque burden and composition on coronary CT angiography (CCTA) compared to the Agatston score (AS)., Methods: We identified 347 men enrolled in the Multicenter AIDS cohort study who underwent contrast and non-contrast CCTs, and had CAC>0. CAC densities (mean Hounsfield Units [HU]) per plaque) and volumes on non-contrast CCT were measured. A Density-Volume Calcium score was calculated by multiplying the plaque volume by a factor based on the mean HU of the plaque (4, 3, 2 and 1 for 130-199, 200-299, 300-399, and ≥400HU). Total Density-Volume Calcium score was determined by the sum of these individual scores. The semi-quantitative partially calcified and total plaque scores (PCPS and TPS) on CCTA were calculated. The associations between Density-Volume Calcium score, PCPS and TPS were examined., Results: Overall, 2879 CAC plaques were assessed. Multivariable linear regression models demonstrated a stronger association between the log Density-Volume Calcium score and both the PCPS (β 0.99, 95%CI 0.80-1.19) and TPS (β 2.15, 95%CI 1.88-2.42) compared to the log of AS (PCPS: β 0.77, 95%CI 0.61-0.94; TPS: β 1.70, 95%CI 1.48-1.94). Similar results were observed for numbers of PC or TP segments., Conclusion: The new CAC score weighted towards lower density demonstrated improved correlation with semi-quantitative PC and TP burden on CCTA compared to the traditional AS, which suggests it has utility as an alternative measure of atherosclerotic burden., (Copyright © 2020 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

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., (© 2020 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of International AIDS Society.)

Objective: To understand the epidemiology of non-AIDS-related chronic comorbidities (NACMs) among aging persons with HIV (PWH)., Design: Prospective multicenter observational study to assess, in an age-stratified fashion, number and types of NACMs by demographic and HIV factors., Methods: Eligible participants were seen during 1 January 1997 to 30 June 2015, followed for more than 5 years, received antiretroviral therapy (ART), and virally suppressed (HIV viral load <200 copies/ml ≥75% of observation time). Age was stratified (18-40, 41-50, 51-60, ≥61 years). NACMs included cardiovascular disease, cancer, hypertension, diabetes, dyslipidemia, arthritis, viral hepatitis, anemia, and psychiatric illness., Results: Of 1540 patients, 1247 (81%) were men, 406 (26%) non-Hispanic blacks (NHB), 183 (12%) Hispanics/Latinos, 575 (37%) with public insurance, 939 (61%) MSM, and 125 (8%) with injection drug use history. By age strata 18-40, 41-50, 51-60, and at least 61 years, there were 180, 502, 560, and 298 patients, respectively. Median HIV Outpatient Study observation was 10.8 years (range: min-max = 5.0-18.5). Mean number of NACMs increased with older age category (1.4, 2.1, 3.0, and 3.9, respectively; P < 0.001), as did prevalence of most NACMs (P < 0.001). Age-related differences in NACM numbers were primarily due to anemia, hepatitis C virus infection, and diabetes. Differences (all P < 0.05) in NACM number existed by sex (women >men, 3.9 vs. 3.4), race/ethnicity (NHB >non-NHB, 3.8 vs. 3.4), and insurance status (public >private, 4.3 vs. 3.1)., Conclusions: Age-related increases existed in prevalence and number of NACMs, with disproportionate burden among women, NHBs, and the publicly insured. These groups should be targeted for screening and prevention strategies aimed at NACM reduction.

Objective: Cardiovascular disease (CVD) is a common cause of morbidity and mortality among persons living with HIV (PLWH). We used individual cardiovascular risk factor profiles to estimate heart age for PLWH in medical care in the United States., Design: Cross-sectional analyses of HIV Outpatient Study (HOPS) data METHODS:: Included in this analysis were participants aged 30-74 years, without prior CVD, with at least two HOPS clinic visits during 2010-2017, at least 1-year of follow-up, and available covariate data. We calculated age and race/ethnicity-adjusted heart age and excess heart age (chronological age - heart age), using a Framingham risk score-based model., Results: We analyzed data from 2467 men and 619 women (mean chronologic age 49.3 and 49.1 years, and 23.6% and 54.6% Non-Hispanic/Latino black, respectively). Adjusted excess heart age was 11.5 years (95% confidence interval, 11.1-12.0) among men and 13.1 years (12.0-14.1) among women. Excess heart age was seen among all age groups beginning with persons aged 30-39 years [men, 7.8 (6.9-8.8); women, 7.7 (4.9-10.4)], with the highest excess heart age among participants aged 50-59 years [men, 13.7 years (13.0-14.4); women, 16.4 years (14.8-18.0)]. More than 50% of participants had an excess heart age of at least 10 years., Conclusions: Excess heart age is common among PLWH, begins in early adulthood, and impacts both women and men. Among PLWH, CVD risk factors should be addressed early and proactively. Routine use of the heart age calculator may help optimize CVD risk stratification and facilitate interventions for aging PLWH.

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.

Background: Risks for cardiovascular diseases, including myocardial infarction and stroke, are elevated in people with HIV infection (PWH). However, no trials of statin utilization with clinical cardiovascular disease (CVD) end points have been completed in PWH, and there are sparse real-world data regarding statin use and lipid-lowering effectiveness. We therefore used a unique cohort of PWH and uninfected controls to evaluate (1) differences in statin types used for PWH versus uninfected persons; (2) lipid lowering achieved by statin use for PWH versus uninfected persons; and (3) racial and ethnic disparities in appropriate statin use among PWH and uninfected persons., Methods: We analyzed a cohort of 5,039 PWH and 10,011 uninfected demographically matched controls who received care at a large urban medical center between January 1, 2000, and May 17, 2017. Medication administration records, prescription data, and validated natural language processing algorithms were used to determine statin utilization. Statins were categorized by generic active ingredient name and intensity (high, moderate, or low). Lipid values collected in routine clinical care were available for analysis. The first set of analyses was restricted to PWH and uninfected matched controls taking statins and compared (1) differences in statin type and (2) difference in cholesterol levels after versus before statin initiation by HIV status. For the second set of analyses, we first used prevalent CVD risk factors to determine participants with statin indications and then determined how many of these participants were taking statins. We then compared statin utilization among persons with indications for statins by race/ethnic group for PWH and uninfected matched controls using multivariable-adjusted logistic regression., Results: Among people prescribed statins, PWH were more likely than controls to have ever taken pravastatin (34.8% vs 12.3%, P < .001) or atorvastatin (72.2% vs 65.6%, P = .002) and less likely to have ever taken simvastatin (14.2% vs 39.5%, P < .001). Among PWH with indications for statin utilization, 55.7% of whites, 39.4% of blacks, and 45.8% of Hispanics were prescribed statins (P < .001). These differences in statin prescription by race/ethnicity remained significant after adjustment for demographics (including insurance status), cardiovascular risk factors, antiretroviral therapy use, HIV viremia, and CD4 count. These racial/ethnic disparities in statin utilization were less pronounced among uninfected persons., Conclusions: Among PWH with statin indication(s), blacks and Hispanics were less likely than whites to have been prescribed a statin. These racial/ethnic disparities were less pronounced among uninfected persons. There were significant differences in type of statin used for PWH compared to uninfected matched controls. Future efforts addressing disparities in CVD prevention among PWH are warranted., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Adults with HIV have an increased burden of non-AIDS-defining cancers, myocardial infarction, end-stage liver disease, and end-stage renal disease. The objective of this study was to estimate the population attributable fractions (PAFs) of preventable or modifiable HIV-related and traditional risk factors for non-AIDS-defining cancers, myocardial infarction, end-stage liver disease, and end-stage renal disease outcomes., Methods: We included participants receiving care in academic and community-based outpatient HIV clinical cohorts in the USA and Canada from Jan 1, 2000, to Dec 31, 2014, who contributed to the North American AIDS Cohort Collaboration on Research and Design and who had validated non-AIDS-defining cancers, myocardial infarction, end-stage liver disease, or end-stage renal disease outcomes. Traditional risk factors were tobacco smoking, hypertension, elevated total cholesterol, type 2 diabetes, renal impairment (stage 4 chronic kidney disease), and hepatitis C virus and hepatitis B virus infections. HIV-related risk factors were low CD4 count (<200 cells per μL), detectable plasma HIV RNA (>400 copies per mL), and history of a clinical AIDS diagnosis. PAFs and 95% CIs were estimated to quantify the proportion of outcomes that could be avoided if the risk factor was prevented., Findings: In each of the study populations for the four outcomes (1405 of 61 500 had non-AIDS-defining cancer, 347 of 29 515 had myocardial infarctions, 387 of 35 044 had end-stage liver disease events, and 255 of 35 620 had end-stage renal disease events), about 17% were older than 50 years at study entry, about 50% were non-white, and about 80% were men. Preventing smoking would avoid 24% (95% CI 13-35) of these cancers and 37% (7-66) of the myocardial infarctions. Preventing elevated total cholesterol and hypertension would avoid the greatest proportion of myocardial infarctions: 44% (30-58) for cholesterol and 42% (28-56) for hypertension. For liver disease, the PAF was greatest for hepatitis C infection (33%; 95% CI 17-48). For renal disease, the PAF was greatest for hypertension (39%; 26-51) followed by elevated total cholesterol (22%; 13-31), detectable HIV RNA (19; 9-31), and low CD4 cell count (13%; 4-21)., Interpretation: The substantial proportion of non-AIDS-defining cancers, myocardial infarction, end-stage liver disease, and end-stage renal disease outcomes that could be prevented with interventions on traditional risk factors elevates the importance of screening for these risk factors, improving the effectiveness of prevention (or modification) of these risk factors, and creating sustainable care models to implement such interventions during the decades of life of adults living with HIV who are receiving care., Funding: National Institutes of Health, US Centers for Disease Control and Prevention, the US Agency for Healthcare Research and Quality, the US Health Resources and Services Administration, the Canadian Institutes of Health Research, the Ontario Ministry of Health and Long Term Care, and the Government of Alberta., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: HIV-infected (HIV+) persons are at increased risk of chronic kidney disease, but serum creatinine does not detect early losses in kidney function. We hypothesized that urine biomarkers of kidney damage would be associated with subsequent changes in kidney function in a contemporary cohort of HIV+ and HIV-uninfected (HIV-) men., Methods: In the Multicenter AIDS Cohort Study, we measured baseline urine concentrations of 5 biomarkers from 2009 to 2011 in 860 HIV+ and 337 HIV- men: albumin, alpha-1-microglobulin (α1m), interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1), and procollagen type III N-terminal propeptide (PIIINP). We evaluated associations of urine biomarker concentrations with annual changes in estimated glomerular filtration rate (eGFR) using multivariable linear mixed models adjusted for demographics, traditional kidney disease risk factors, HIV-related risk factors, and baseline eGFR., Results: Over a median follow-up of 4.8 years, the average annual eGFR decline was 1.42 mL/min/1.73 m2/year in HIV+ men and 1.22 mL/min/1.73 m2/year in HIV- men. Among HIV+ men, the highest vs. lowest tertiles of albumin (-1.78 mL/min/1.73 m2/year, 95% CI -3.47 to -0.09) and α1m (-2.43 mL/min/1.73 m2/year, 95% CI -4.14 to -0.73) were each associated with faster annual eGFR declines after multivariable adjustment. Among HIV- men, the highest vs. lowest tertile of α1m (-2.49 mL/min/1.73 m2/year, 95% CI -4.48 to -0.50) was independently associated with faster annual eGFR decline. Urine IL-18, KIM-1, and PIIINP showed no independent associations with eGFR decline, regardless of HIV serostatus., Conclusions: Among HIV+ men, higher urine albumin and α1m are associated with subsequent declines in kidney function, independent of eGFR., (© 2019 S. Karger AG, Basel.)

Objective: Sexual HIV transmission is more likely to occur when plasma HIV RNA level (viral load) exceeds 1500 copies/ml. We assessed the percentage of person-time spent with viral load above 1500 copies/ml (pPT >1500) among adults with HIV in care., Design: Observational cohort in eight United States HIV clinics., Methods: Participants had at least one HIV Outpatient Study (HOPS) clinic visit and at least two viral loads during 2000-2014. We assessed pPT above 1500 in time intervals between consecutive viral load pairs, overall and by ART status. Trends in pPT above 1500 and associations between pPT above 1500 and chosen baseline demographics and clinical characteristics were analyzed using generalized estimating equations., Results: There were 5873 patients contributing 37 794 person-years; 86.0% person-years had prescribed ART, with increasing coverage over time. Over 2000-2014 pPT above 1500 was 24.2%, decreasing from 38.3% in 2000-2002 to 11.3% in 2012-2014. During observation time with ART prescribed, pPT above 1500 was 16.4% overall, decreasing from 29.9% in 2000-2002 to 8.0% in 2012-2014. pPT above 1500 was higher in patients less than 35 vs. at least 50 years old (31.5 vs. 15.6%), women vs. men (30.8 vs. 22.3%), and black vs. white and Latino/Hispanic patients (32.7 vs. 19.9 and 23.7%, respectively). Multivariable correlates of higher pPT above 1500 included no prescribed ART, being younger, non-Hispanic black vs. white, baseline viral load above 1500 copies/ml or lower CD4 count, and baseline public vs. private insurance., Conclusion: pPT above 1500 declined during 2000-2014. Results support decreasing HIV transmission risk from persons in HIV care over the last decade, and the need to focus interventions on patient groups more consistently viremic.

Objectives: To determine the relationship between glycemic status and cognitive performance in men living with HIV (MLWH) and without HIV infection., Design: A prospective HIV/AIDS cohort study in four US cities between 1999 and 2016., Methods: Glycemic status was categorized as normal glucose, impaired fasting glucose, controlled diabetes mellitus and uncontrolled diabetes mellitus at each semiannual visit. Cognitive performance was evaluated using nine neuropsychological tests which measure attention, constructional ability, verbal learning, executive functioning, memory and psychomotor speed. Linear mixed models were used to assess the association between glycemic status and cognition., Results: Overall, 900 MLWH and 1149 men without HIV were included. MLWH had significantly more person-visits with impaired fasting glucose (52.1 vs. 47.9%) and controlled diabetes mellitus (58.2 vs. 41.8%) than men without HIV (P < 0.05). Compared with men with normal glucose, men with diabetes mellitus had significantly poorer performance on psychomotor speed, executive function and verbal learning (all P < 0.05). There was no difference in cognition by HIV serostatus. The largest effect was observed in individuals with uncontrolled diabetes mellitus throughout the study period, equivalent to 16.5 and 13.4 years of aging on psychomotor speed and executive function, respectively, the effect of which remained significant after adjusting for HIV-related risk factors. Lower CD4+ nadir was also associated with worse cognitive performance., Conclusion: Abnormalities in glucose metabolism were more common among MLWH than men without HIV and were related to impaired cognitive performance. Metabolic status, along with advanced age and previous immunosuppression, may be important predictors of cognition in the modern antiretroviral therapy era.

People living with HIV (PLWH) are diagnosed with cancer at an increased rate over the general population and generally have a higher mortality due to delayed diagnoses, advanced cancer stage, comorbidities, immunosuppression, and cancer treatment disparities. Lack of guidelines and provider education has led to substandard cancer care being offered to PLWH. To fill that gap, the NCCN Guidelines for Cancer in PLWH were developed; they provide treatment recommendations for PLWH who develop non-small cell lung cancer, anal cancer, Hodgkin lymphoma, and cervical cancer. In addition, the NCCN Guidelines outline advice regarding HIV management during cancer therapy; drug-drug interactions between antiretroviral treatments and cancer therapies; and workup, radiation therapy, surgical management, and supportive care in PLWH who have cancer., (Copyright © 2018 by the National Comprehensive Cancer Network.)

Background: Age-associated conditions are increasingly common among persons living with human immunodeficiency virus (HIV) (PLWH). A longitudinal investigation of their accrual is needed given their implications on clinical care complexity. We examined trends in the co-occurrence of age-associated conditions among PLWH receiving clinical care, and differences in their prevalence by demographic subgroup., Methods: This cohort study was nested within the North American AIDS Cohort Collaboration on Research and Design. Participants from HIV outpatient clinics were antiretroviral therapy-exposed PLWH receiving clinical care (ie, ≥1 CD4 count) in the United States during 2000-2009. Multimorbidity was irreversible, defined as having ≥2: hypertension, diabetes mellitus, chronic kidney disease, hypercholesterolemia, end-stage liver disease, or non-AIDS-related cancer. Adjusted prevalence ratios (aPR) and 95% confidence intervals (CIs) comparing demographic subgroups were obtained by Poisson regression with robust error variance, using generalized estimating equations for repeated measures., Results: Among 22969 adults, 79% were male, 36% were black, and the median baseline age was 40 years (interquartile range, 34-46 years). Between 2000 and 2009, multimorbidity prevalence increased from 8.2% to 22.4% (Ptrend < .001). Adjusting for age, this trend was still significant (P < .001). There was no difference by sex, but blacks were less likely than whites to have multimorbidity (aPR, 0.87; 95% CI, .77-.99). Multimorbidity was the highest among heterosexuals, relative to men who have sex with men (aPR, 1.16; 95% CI, 1.01-1.34). Hypertension and hypercholesterolemia most commonly co-occurred., Conclusions: Multimorbidity prevalence has increased among PLWH. Comorbidity prevention and multisubspecialty management of increasingly complex healthcare needs will be vital to ensuring that they receive needed care.

In the United States, women accounted for 19% of new HIV diagnoses in 2015 and were less likely to reach virologic suppression when compared to men. We assessed trends and disparities in virologic suppression among HIV-positive women to inform HIV treatment strategies. Data were from a prospective cohort of the HIV Outpatient Study and collected at nine United States HIV clinics. We included women aged ≥18 years, with ≥1 visit, who were prescribed antiretroviral therapy, and had ≥1 viral load test performed between 2010 and 2015. We defined virologic suppression as viral load <50 copies/mL and calculated adjusted prevalence ratios (aPR) with 95% confidence intervals (CI) for virologic suppression by race/ethnicity and year of measure. Generalized estimating equations were used for multivariable analyses to assess factors associated with virologic suppression. Among 809 women (median age = 44 years), 482 (60%) were black, 177 (22%) white, 150 (19%) Hispanic/Latina. Virologic suppression was less prevalent among black women (73%) compared with Hispanic/Latina women (83%) and white women (91%). In multivariable analyses, not achieving virologic suppression was more likely among black women (aPR = 2.13; CI = 1.50-3.02) or Hispanic/Latina women (aPR = 1.66; CI = 1.08-2.56) compared with white women, and among women who attended public clinics (aPR = 1.42; CI = 1.07-1.87) compared with those who attended a private clinic. Between 2010 and 2015, virologic suppression among HIV-positive women increased from 68% to 83%, but racial/ethnic disparities persisted. Black and Hispanic/Latina women had significantly lower rates of virologic suppression than white women. Interventions targeting virologic suppression improvement among HIV-positive women of color, especially those who attend public clinics, are warranted.

Vitamin D may play an important role in a range of disease processes. In the general population, lower vitamin D levels have been associated with kidney dysfunction. HIV-infected populations have a higher risk of chronic kidney disease. Few studies have examined the link between lower vitamin D levels and kidney function decline among HIV-infected persons. We investigated the associations of serum 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH) 2 D] with kidney function decline in a cohort of HIV-infected white and black men under highly active antiretroviral therapy treatment in the vitamin D ancillary study of the Multicenter AIDS Cohort Study. The associations of 25(OH)D and 1,25(OH) 2 D with annual change in estimated glomerular filtration rate (eGFR) were evaluated using linear mixed effects models. This study included 187 whites and 86 blacks with vitamin D measures and eGFR ≥60 ml/min/1.73 m 2 at baseline. Over a median follow-up of 8.0 years, lower 25(OH)D levels were significantly associated with faster eGFR decline in whites (adjusted annual change in eGFR, tertile 1: -2.06 ml/min/1.73 m 2 vs. tertile 3: -1.23 ml/min/1.73 m 2 , p trend .03), while no significant association was detected in blacks. Lower 1,25(OH) 2 D was associated with faster kidney function decline in both whites and blacks, although the estimates were not statistically significant. In conclusion, lower 25(OH)D levels were significantly associated with faster eGFR decline in a cohort of HIV-infected white men, but not in those with black ancestry. Further research is warranted to investigate the association of 25(OH)D and 1,25(OH) 2 D with kidney function decline in larger and ethnically diverse populations.

Background: Hepatitis C virus (HCV) infection may increase the risk of cardiovascular disease (CVD). We evaluated the association of chronic HCV infection and coronary atherosclerosis among participants in the Multicenter AIDS Cohort Study., Methods: We assessed 994 men with or without human immunodeficiency virus (HIV) infection (87 of whom had chronic HCV infection) for coronary plaque, using noncontrast coronary computed tomography (CT); 755 also underwent CT angiography. We then evaluated the associations of chronic HCV infection and HIV infection with measures of plaque prevalence, extent, and stenosis., Results: After adjustment for demographic characteristics, HIV serostatus, behaviors, and CVD risk factors, chronic HCV infection was significantly associated with a higher prevalence of coronary artery calcium (prevalence ratio, 1.29; 95% confidence interval [CI], 1.02-1.63), any plaque (prevalence ratio, 1.26; 95% CI, 1.09-1.45), and noncalcified plaque (prevalence ratio, 1.42; 95% CI, 1.16-1.75). Chronic HCV infection and HIV infection were independently associated with the prevalence of any plaque and of noncalcified plaque, but there was no evidence of a synergistic effect due to HIV/HCV coinfection. The prevalences of coronary artery calcium, any plaque, noncalcified plaque, a mixture of noncalcified and calcified plaque, and calcified plaque were significantly higher among men with an HCV RNA load of ≥2 × 10(6) IU/mL, compared with findings among men without chronic HCV infection., Conclusions: Chronic HCV infection is associated with subclinical CVD, suggesting that vigilant assessments of cardiovascular risk are warranted for HCV-infected individuals. Future research should determine whether HCV infection duration or HCV treatment influence coronary plaque development., (© The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Background: Although modern combination antiretroviral therapy (cART) regimens are better tolerated and less complex than earlier treatments, regimen modification or discontinuation remains a concern., Methods: We studied HIV Outpatient Study (HOPS) participants who initiated the first or second cART regimens during: 1996-1999, 2000-2003, 2004-2007, and 2008-2011. We analyzed regimen durability (time to regimen modification) and success (achieving undetectable plasma HIV RNA) for the first and second cART regimens using Kaplan-Meier curves and log-rank tests, and examined factors associated with durability and success of the first cART regimen using proportional hazards models., Results: Durability of cART was progressively longer for cART regimens initiated in more recent periods: median first cART regimen durations were 1.0, 1.1, 2.1, and 4.6 years in 1996-1999, 2000-2003, 2004-2007, and 2008-2011, and the median second cART durations were 0.9, 1.2, 2.8, and 3.9 years, respectively (both P < 0.001). Comparing 1996-1999 and 2008-2011, the percentage of patients who achieved an undetectable HIV RNA within 6 months of first cART initiation increased from 65% to 81% and from 63% to 80% on second cART (both P < 0.001). Among patients initiating first cART during 2008-2011, black non-Hispanic/Latino race/ethnicity and ≥ twice-daily dosing were significantly associated with higher rates of regimen modification (P < 0.05), and higher baseline HIV RNA levels were associated with failure to achieve an undetectable HIV RNA (P < 0.001)., Conclusions: Among HIV-infected U.S. adults in routine HIV care, durability of the first and second cART regimens and the likelihood of prompt virological suppression increased during 1996-2011, coincident with the availability of more tolerable, less complex cART options.

Previous studies demonstrated that blacks have less coronary artery calcification (CAC) than whites. We evaluated racial differences in plaque composition and stenosis in the Multicenter AIDS Cohort Study. HIV-positive and HIV-negative men underwent noncontrast cardiac computed tomography (CT) if they were aged 40 to 70 years, weighed <136 kg, and had no history of cardiac surgery or revascularization and, if eligible, coronary CT angiography (CTA). There were 1,001 men who underwent CT scans and 759 men CTA. We measured CAC on noncontrast CT and identified total plaque, noncalcified plaque, calcified plaque, mixed plaque, and coronary stenosis >50% on CTA. The association of presence and extent of plaque with race was determined after adjustment for HIV serostatus, cardiovascular risk factors, and measures of socioeconomic status. The prevalences of any plaque on CTA and noncalcified plaque were not different between black and white men; however, black men had lower prevalences of CAC (prevalence ratio [PR] 0.79, p = 0.01), calcified plaque (PR 0.69, p = 0.002), and stenosis >50% (PR 0.59, p = 0.009). There were no associations between black race and extent of plaque in fully adjusted models. Using log-linear regression, black race was associated with a lower extent of any plaque on CTA in HIV-positive men (estimate = -0.24, p = 0.051) but not in HIV-negative men (0.12, p = 0.50, HIV interaction p = 0.005). In conclusion, a lower prevalence of CAC in black compared with white men appears to reflect less calcification of plaque and stenosis rather than a lower overall prevalence of plaque., (Copyright © 2014 Elsevier Inc. All rights reserved.)

We analyzed 369 patients with no prior Mycobacterium avium complex (MAC) infection and CD4 <50 cells/μL (baseline), while on combination antiretroviral therapy(cART), for incidence rates of primary MAC infection during the 6 months after baseline, by prophylaxis status. Of participants (median age, 40 years old), most were male (81%) and about half were non-white; at baseline, 81% of participants were on cART >60 days and 19% had HIV RNA <1000 copies/mL, whereas 65% had HIV RNA >10,000 copies/mL. Eleven patients had MAC infection within 6 months baseline (rate=0.6/100 person months): 4/175 on MAC prophylaxis vs. 7/194, no MAC prophylaxis (p=0.64). Of the 11 patients, seven had HIV RNA >10,000, and three >1000-9999 copies/mL at baseline (one missing). Median time to MAC infection was 62 days (IQR 43-126, maximum 139 days). No MAC infection occurred among 71 (19%) patients virologically suppressed (HIV RNA <1000 copies/mL) at baseline, including 41 patients with no MAC prophylaxis during follow-up. A small number of eligible virologically suppressed participants and the lack of data on cART/MAC prophylaxis adherence limited our observational nonrandomized study. Primary MAC prophylaxis may not be required for cART-virologically suppressed patients with CD4 <50 cells/mL.

Background: Certain sociodemographic subgroups of HIV-infected patients may experience more chronic disease than others due to behavioural risk factors, advanced HIV disease or complications from extended use of combination antiretroviral therapy (cART), but recent comparative data are limited., Methods: We studied HIV-infected adult patients in care during 2006-2010 who had been prescribed ≥ 6 months of cART. We analysed the prevalence of selected key chronic conditions and polymorbidity (having 2 or more out of 10 key conditions) by gender and race/ethnicity., Results: Of the 3,166 HIV-infected patients (median age 47 years, CD4⁺ T-cell count 496 cells/mm³, duration of cART use 6.8 years), 21% were female, 57% were non-Hispanic White and over half were current or former tobacco smokers. The five most frequent conditions among women (median age 45 years) were dyslipidaemia (67.3%), hypertension (57.4%), obesity (31.7%), viral hepatitis B or C coinfection (29.0%) and low high-density lipoprotein cholesterol (HDLc; 27.3%). The five most frequent conditions in men (median age 47 years) were dyslipidaemia (81.2%), hypertension (54.4%), low HDLc (41.1%), elevated triglycerides (32.3%) and elevated non-HDLc (26.8%). In multivariable analyses, Hispanic patients had higher prevalence of obesity and diabetes than White patients; Black patients had higher prevalence of obesity and hypertension but lower rates of lipid abnormalities. Of all patients, 73.7% of women and 66.8% of men had polymorbidity, with no evidence of disparities by race/ethnicity., Conclusions: Among contemporary cART-treated HIV-infected adults, chronic conditions and polymorbidity were common, underscoring the importance of chronic disease prevention and management among ageing HIV-infected patients.

Objective: To describe incidence of immune reconstitution inflammatory syndrome (IRIS) and its association with mortality in a large multisite US HIV-infected cohort applying an objective, comprehensive definition., Design: We studied 2,610 patients seen during 1996-2007 who initiated or resumed highly active combination antiretroviral therapy (cART) and, during the next 6 months, demonstrated a decline in plasma HIV-RNA viral load of at least 0.5 log(10) copies/ml or an increase of at least 50% in CD4 cell count per microliter. We defined IRIS as the diagnosis of a type B or C condition [as per the Centers for Disease Control and Prevention (CDC) 1993 AIDS case definition] or any new mucocutaneous disorder during this same 6-month period., Methods: We assessed the incidence of IRIS and evaluated risk factors for IRIS using conditional logistic regression and for all-cause mortality using proportional hazards models., Results: We identified 370 cases of IRIS (in 276 patients). Median and nadir CD4 cell counts at cART initiation were 90 and 43 cells/μl, respectively; median viral load was 2.7 log(10) copies/ml. The most common IRIS-defining diagnoses were candidiasis (all forms), cytomegalovirus infection, disseminated Mycobacterium avium intracellulare, Pneumocystis pneumonia, varicella zoster, Kaposi's sarcoma and non-Hodgkin lymphoma. Only one case of Mycobacterium tuberculosis was observed. IRIS was independently associated with CD4 cell count less than 50 cells/μl vs. at least 200 cells/μl [odds ratio (OR) 5.0] and a viral load of at least 5.0 log(10) copies vs. less than 4.0 log(10) copies (OR 2.3). IRIS with a type B-defining or type C-defining diagnosis approximately doubled the risk for all-cause mortality., Conclusion: In this large US-based HIV-infected cohort, IRIS occurred in 10.6% of patients who responded to effective ART and contributed to increased mortality.

Objective: Understanding mortality differences among HIV-infected patients can focus efforts to improve survival., Design: We evaluated death rates, causes, and associated factors among treated patients in the HIV Outpatient Study (HOPS), a large, prospective, multicenter observational cohort of HIV-infected persons seen at a diverse set of US sites of care., Methods: Among 3754 HOPS participants seen during 1996-2007 with at least 6 months of follow-up after initiating HAART and receiving HAART at least 75% of time under observation ('substantially treated'), we calculated hazard ratios for death using proportional hazards regression models. We also examined death causes and comorbidities among decedents., Results: Substantially treated participants, followed a median 4.7 years (interquartile range, 2.2-8.5), experienced 331 deaths. In multivariable analyses, higher mortality was associated with an index CD4 cell count less than 200 cells/μl [adjusted hazard ratio (aHR), 2.86; 95% confidence interval (CI) 1.95-4.21], older age (aHR, 1.50 per 10 years; 95% CI 1.33-1.70), log(10)HIV RNA (aHR, 1.67 per log(10); 95% CI 1.51-1.85), but not race/ethnicity (aHR, 0.99 for blacks vs. whites, P = 0.92). Mortality was increased among publicly insured (PUB) vs. privately insured participants (PRV) when index CD4 cell count was at least 200 cells/μl (aHR, 2.03; 95% CI 1.32-3.14) but not when index CD4 cell count was less than 200 cells/μl (aHR, 1.3, P = 0.13). By death cause, PUB had significantly more cardiovascular events and hepatic disorders than PRV. Comorbidities more frequent among PUB vs. PRV decedents included cardiovascular disease, renal impairment, and chronic hepatitis., Conclusion: Among HAART-treated participants with CD4 cell counts at least 200 cells/μl, PUB experienced higher death rates than PRV. Non-AIDS death and disease causes predominated among publicly insured decedents, suggesting that treatable comorbidities contributed to survival disparities.

An optimal measurement of glomerular filtration rate (GFR) should minimize the number of blood draws, and reduce procedural invasiveness and the burden to study personnel and cost, without sacrificing accuracy. Equations have been proposed to calculate GFR from the slow compartment separately for adults and children. To develop a universal equation, we used 1347 GFR measurements from two diverse groups consisting of 527 men in the Multicenter AIDS Cohort Study and 514 children in the Chronic Kidney Disease in Children cohort. Both studies used nearly identical two-compartment (fast and slow) protocols to measure GFR. To estimate the fast component from markers of body size and of the slow component, we used standard linear regression methods with the log-transformed fast area as the dependent variable. The fast area could be accurately estimated from body surface area by a simple parameter (6.4/body surface area) with no residual dependence on the slow area or other markers of body size. Our equation measures only the slow iohexol plasma disappearance curve with as few as two time points and was normalized to 1.73 m2 body surface area. It is of the form: GFR=slowGFR/[1+0.12(slowGFR/100)]. In a random sample utilizing a third of the patients for validation, there was excellent agreement between the calculated and measured GFR with low root mean square errors being 4.6 and 1.5 ml/min per 1.73 m2 for adults and children, respectively. Thus, our proposed simple equation, developed in a combined patient group with a broad range of GFRs, may be applied universally and is independent of the injected amount of iohexol.

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 or= 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.

Objectives: To assess the incidence and spectrum of AIDS-defining opportunistic illnesses in the highly active antiretroviral therapy (cART) era., Design: A prospective cohort study of 8070 participants in the HIV Outpatient Study at 12 U.S. HIV clinics., Methods: We calculated incidence rates per 1000 person-years of observation for the first opportunistic infection, first opportunistic malignancy, and first occurrence of each individual opportunistic illness during 1994-2007. Using stratified Poisson regression models, and adjusting for sex, race, and HIV risk category, we modeled annual percentage changes in opportunistic illness incidence rates by calendar period., Results: Eight thousand and seventy patients (baseline median age 38 years; median CD4 cell count 298 cells/microl) experienced 2027 incident opportunistic illnesses during a median of 2.9 years of observation. During 1994-1997, 1998-2002, and 2003-2007, respectively, rates of opportunistic infections (per 1000 person-years) were 89.0, 25.2 and 13.3 and rates of opportunistic malignancies were 23.4, 5.8 and 3.0 (P for trend <0.001 for both). Opportunistic illness rate decreases were similar for the subset of patients receiving cART. During 2003-2007, there were no significant changes in annual rates of opportunistic infections or opportunistic malignancies; the leading opportunistic illnesses (rate per 1000 person-years) were esophageal candidiasis (5.2), Pneumocystis pneumonia (3.9), cervical cancer (3.5), Mycobacterium avium complex infection (2.5), and cytomegalovirus disease (1.8); 36% opportunistic illness events occurred at CD4 cell counts at least 200 cells/microl., Conclusions: Opportunistic illness rates declined precipitously after introduction of cART and stabilized at low levels during 2003-2007. In this contemporary cART era, a third of opportunistic illnesses were diagnosed at CD4 cell counts at least 200 cells/microl.

Background: The risk of diabetes mellitus (DM) in human immunodeficiency virus (HIV)-infected patients receiving highly active antiretroviral therapy (HAART) has not been well defined., Methods: We conducted an analysis in the Multicenter AIDS Cohort Study to determine the prevalence and incidence of DM in this cohort of HIV-infected and HIV-seronegative men. Prevalence analysis included 1278 men (710 HIV seronegative and 568 HIV infected, 411 receiving HAART) with fasting glucose concentration determinations at baseline. Incidence analysis included 680 of these 1278 men who at the baseline visit had a fasting glucose concentration of 98 mg/dL (5.4 mmol/L) or less, no self-reported history of DM, and no self-reported use of antidiabetic medication. Diabetes mellitus was defined as a fasting glucose concentration of 126 mg/dL (7 mmol/L) or higher, self-reported diagnosis of DM, or self-reported use of antidiabetic medication., Results: Fifty-seven (14%) of the 411 HIV-infected men using HAART at the baseline visit had prevalent DM compared with 33 (5%) of the 711 HIV-seronegative men (prevalence ratio = 4.6; 95% confidence interval, 3.0-7.1, adjusted for age and body mass index [calculated as weight in kilograms divided by the square of height in meters]). The rate of incident DM was 4.7 cases per 100 person-years among HIV-infected men using HAART compared with 1.4 cases per 100 person-years among HIV-seronegative men (rate ratio = 4.11; 95% confidence interval, 1.85-9.16, adjusted for age and body mass index), during the 4-year observation period, based on a median follow-up of 2.3 years., Conclusion: The incidence of DM in HIV-infected men with HAART exposure was greater than 4 times that of HIV-seronegative men, representing a risk that is higher than previous estimates.

Study Objectives: We evaluated differences in processes and outcomes of HIV-related pneumonia care among patients in Veterans Affairs (VA), public, and for-profit and not-for-profit private hospitals in the United States. We compared the results of our current study (1995 to 1997) with those of our previous study that included a sample of patients receiving care during the years 1987 to 1990 to determine how HIV-related pneumonia care had evolved over the last decade., Setting/patients: The sample consisted of 1,231 patients with HIV infection who received care for Pneumocystis carinii pneumonia (PCP) and 750 patients with HIV infection who received care for community-acquired pneumonia (CAP) during the years 1995 to 1997., Measurement: We conducted a retrospective medical record review and evaluated patient and hospital characteristics, HIV-related processes of care (timely use of anti-PCP medications, adjunctive corticosteroids), non-HIV-related processes of care (timely use of CAP treatment medications, diagnostic testing, ICU utilization, rates of endotracheal ventilation, placement on respiratory isolation), length of inpatient hospital stay, and inpatient mortality., Results: Rates of timely use of antibiotics and adjunctive corticosteroids for treating PCP were high and improved dramatically from the prior decade. However, compliance with consensus guidelines that recommend < 8 h as the optimal time window for initiation of antibiotics to treat CAP was lower. For both PCP and CAP, variations in processes of care and lengths of in-hospital stays, but not mortality rates, were noted at VA, public, private not-for-profit hospitals, and for-profit hospitals., Conclusions: This study provides the first overview of HIV-related pneumonia care in the early highly active antiretroviral therapy era, and contrasts current findings with those of a similarly conducted study from a decade earlier. Quality of care for patients with PCP improved, but further efforts are needed to facilitate the appropriate management of CAP. In the third decade of the epidemic, it will be important to monitor whether variations in processes of care for various HIV-related clinical diagnoses among different types of hospitals persist.