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Introduction: Socioeconomic status (SES) influences well-being among people living with HIV (people with HIV [PWH]); when individual-level SES information is not available, area-level SES indicators may be a suitable alternative. We hypothesized that (1) select ZIP code-level SES indicators would be associated with viral suppression and (2) accounting for ZIP code-level SES would attenuate racial disparities in viral suppression among PWH., Setting: The NA-ACCORD, a collaboration of clinical and interval cohorts of PWH, was used., Methods: Participants with ≥1 viral load measurement and ≥1 US residential 5-digit ZIP code(s) between 2010 and 2018 were included. In this serial cross-sectional analysis, multivariable logistic regression models were used to quantify the annual association of race and ethnicity with viral suppression, in the presence of SES indicators and sex, hepatitis C status, and age., Results: We observed a dose-response relationship between SES factors and viral suppression. Lower income and education were associated with 0.5-0.7-fold annual decreases in odds of viral suppression. We observed racial disparities of approximately 40% decreased odds of viral suppression among non-Hispanic Black compared with non-Hispanic White participants. The disparity persisted but narrowed by 3%-4% when including SES in the models., Conclusions: ZIP code-based SES was associated with viral suppression, and accounting for SES narrowed racial disparities in viral suppression among PWH in the NA-ACCORD. Inclusion of ZIP code-level indicators of SES as surrogates for individual-level SES should be considered to improve our understanding of the impact of social determinants of health and racial disparities on key outcomes among PWH in North America., Competing Interests: J.G. is an ad hoc member of HIV national advisory boards to Merck, Gilead, and ViiV Health. K.V.C.M. has received consultation fees from Eli Lilly, Bayer, Gilead Sciences, Merck, and ViiV. P.R. has received consultation fees from Gilead and Janssen. K.N.A. serves on the scientific advisory board for TrioHealth, Inc. The remaining authors have no conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Anemia is an independent predictor of mortality, which may be utilized as a signal of deteriorating health. We estimated the association between anemia severity categories and mortality following the initiation of antiretroviral therapy (ART) among people with HIV (PWH) in North America., Methods: Within the NA-ACCORD, annual median hemoglobin measurements between 01/01/2007-12/31/2016 were categorized using World Health Organization criteria into mild (11.0-12.9g/dL men, 11.0-11.9g/dL women), moderate (8.0-10.9g/dL men/women) and severe (<8.0g/dL men/women) anemia. Discrete time-to-event analyses using complementary log-log link models estimated mortality hazards ratios adjusted for demographics, comorbidities, and HIV clinical markers with 95% confidence intervals for the association between anemia and mortality., Results: Among 67,228 PWH contributing a total of 320,261 annual median hemoglobin measurements, 257,293 (80%) demonstrated no anemia, 44,041 (14%) mild, 18,259 (6%) moderate, and 668 (0.2%) severe anemia during follow-up. Mortality risk was 5.6-fold higher among PWH with (vs. without) anemia. The association was greater among males (aHR=5.8 [5.4, 6.2]) versus females (aHR=4.1 [3.2, 5.4]). Mortality risk was 3.8-fold higher among PWH with mild anemia, 13.7-fold higher with moderate anemia, and 34.5-fold higher with severe anemia (vs. no anemia). Median hemoglobin levels significantly declined within 4 years prior to death, with the maximum decrease the year prior to death. Macrocytic anemia was associated with an increased and microcytic anemia a decreased mortality risk (vs. normocytic anemia)., Conclusions: Anemia among PWH who have initiated ART is an important predictive marker for mortality with macrocytic anemia having an increased and microcytic anemia a decreased association with mortality compared with normocytic anemia., Competing Interests: Conflicts of Interest/Competing interests: Dr. Althoff is a consultant to the All of Us Research Program and serves on the scientific advisory board for Trio Health. Dr. Gill serves as an ad hoc advisor on Canadian National HIV advisory boards of Merck, Gilead and ViiV.Dr. Gebo is a paid consultant for the Aspen Institute, UptoDate and Teach for America. Dr. Thorne is a paid consultant for Gilead and UptoDate. All other authors have no conflicts to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Greater decline in bone health among people with HIV (PWH) has been documented but fracture risk and the impact of specific antiretroviral therapy (ART) regimens remain unclear., Setting: Retrospective analyses of electronic health record data from 3 US integrated health care systems., Methods: Fracture incidence was compared between PWH aged 40 years or older without prior fracture and demographically matched people without HIV (PWoH), stratified by age, sex, and race/ethnicity. Multivariable Cox proportional hazards models were used to estimate fracture risk associated with HIV infection. The association of tenofovir disoproxil fumarate (TDF) use and fracture risk was evaluated in a subset of PWH initiating ART., Results: Incidence of fracture was higher in PWH [13.6/1000 person-years, 95% confidence interval (CI): 13.0 to 14.3, n = 24,308] compared with PWoH (9.5, 95% CI: 9.4 to 9.7, n = 247,313). Compared with PWoH, the adjusted hazard ratio (aHR) for fracture among PWH was 1.24 (95% CI: 1.18 to 1.31). The association between HIV infection and fracture risk increased with age, with the lowest aHR (1.17, 95% CI: 1.10 to 1.25) among those aged 40-49 years and the highest aHR (1.89, 95% CI: 1.30 to 2.76) among those aged 70 years or older. Among PWH initiating ART (n = 6504), TDF was not associated with significant increase in fracture risk compared with non-TDF regimens (aHR: 1.18, 95% CI: 0.89 to 1.58)., Conclusions: Among people aged 40 years or older, HIV infection is associated with increased risk of fractures. Bone health screening from the age of 40 years may be beneficial for PWH. Large cohort studies with longer follow-up are needed to evaluate TDF effect and the potential benefit of early screening., Competing Interests: M.J.S., W.J.T., and M.A.H. received research funding for this study from Gilead Sciences, Inc. R.C.H. received research funding from Gilead Sciences, Inc. for an unrelated study. H.Z. received research funding from Merck for an unrelated study. W.J.T. received research funding from Pfizer, ViiV, Merck, Janssen, Moderna, and GlaxoSmithKline for unrelated studies. The remaining authors have no conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Polypharmacy for multiple chronic conditions (MCCs) poses an increasing challenge in people with HIV (PWH). This research explores medication adherence in PWH with MCCs before and during COVID-19., Setting: Kaiser Permanente Mid-Atlantic States., Methods: Medical and pharmacy records of a continuously enrolled cohort (September 2018-September 2021) of adult PWH were used. To estimate medication adherence, monthly proportion of days covered (PDC) was measured individually for antiretrovirals (ARVs), diabetes medications (DMs), renin-angiotensin antagonists (RASMs), and statins (SMs) and combined into composite measures (CMs) with and without ARVs. Descriptive statistics, time-series models, and multivariable population-averaged panel general estimating equations were used to profile trends, effects, and factors associated with adherence., Results: The cohort (n = 543) was predominantly 51-64 years old (59.3%), Black (73.1%), male (69.2%), and commercially insured (65.4%). Two-thirds (63.7%) of patients were taking medications in 2 medication groups (ie, ARVs and either DMs, RASMs, or SMs), 28.9% were taking medications in 3 medication groups, and 7.4% were taking medications in all 4 medication groups. Overall, PDC for CMs without ARVs was 77.2% and 70.2% with ARVs. After March 2020, negative monthly trends in PDC were observed for CMs without ARVs (β = -0.1%, P = 0.003) and with ARVs (β = -0.3%, P = 0.001). For CMs with ARVs, Black race (aOR = 0.5; P < 0.001; ref: White) and taking medications for 3 medication groups (aOR = 0.8; P < 0.02; ref: 2) were associated with lower adherence., Conclusion: Decreasing medication adherence trends were observed during the COVID-19 pandemic with variations among population subgroups. Opportunity exists to improve medication adherence for non-White populations and those taking medications for MCCs beyond ARVs., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: We characterized trends in statin eligibility and subsequent statin initiation among people with HIV (PWH) from 2001 to 2017 and identified predictors of statin initiation between 2014 and 2017., Setting: PWH participating in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) enrolled in 12 US cohorts collecting data on statin eligibility criteria/prescriptions from 2001 to 2017., Methods: We determined the annual proportion eligible for statins, initiating statins, and median waiting time (from statin eligibility to initiation). Eligibility was defined using ATP III guidelines (2001-2013) and ACC/AHA guidelines (2014-2017). We assessed initiation predictors in 2014-2017 among statin-eligible PWH using Poisson regression, estimating adjusted prevalence ratios (aPRs) with 95% confidence intervals (95% CIs)., Results: Among 16,409 PWH, 7386 (45%) met statin eligibility criteria per guidelines (2001-2017). From 2001 to 2013, statin eligibility ranged from 22% to 25%. Initiation increased from 13% to 45%. In 2014, 51% were statin-eligible, among whom 25% initiated statins, which increased to 32% by 2017. Median waiting time to initiation among those we observed declined over time. Per 10-year increase in age, initiation increased 46% (aPR 1.46, 95% CI: 1.29 to 1.67). Per 1-year increase in calendar year from 2014 to 2017, there was a 41% increase in the likelihood of statin initiation (aPR 1.41, 95% CI: 1.25 to 1.58)., Conclusions: There is a substantial statin treatment gap, amplified by the 2013 ACC/AHA guidelines. Measures are warranted to clarify reasons we observe this gap, and if necessary, increase statin use consistent with guidelines including efforts to help providers identify appropriate candidates., Competing Interests: K.N.A. is a consultant to the All of Us Study (NIH) and serves on the scientific advisory board for TrioHealth. F.J.P. is a consultant and/or on the Speakers' Bureau for Gilead Sciences, Janssen, ViiV, and Merck. M.J.S. had a research grant to his institution from Gilead Sciences, Inc. J.C.M. has a pending research grant paid to his institution from Gilead Sciences, Inc. The remaining authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: HIV is an independent risk factor for heart failure (HF). However, the association of HIV severity with incident HF and the potential interaction with sex are incompletely understood., Setting: Integrated health care system., Methods: We conducted a cohort study of people with HIV (PWH) and matched people without HIV (PWoH), all aged ≥ 21 years and with no previous HF. Poisson regression was used to compare incident HF by HIV status, with PWH stratified by severity of HIV infection [defined by recent (<6 months) CD4 count, nadir CD4 count, or recent HIV RNA level]. Models were adjusted for sociodemographic characteristics, substance use, and HF risk factors. Analyses were conducted for men and women combined, then by sex., Results: The study included 38,868 PWH and 386,569 PWoH (mean baseline age = 41.0 ± 10.8 years; 88% men). Compared with PWoH, incident HF risk was higher among PWH with lower recent CD4 [200-499 cells/µL, adjusted rate ratio (aRR) = 1.82, 95% confidence interval (CI) = 1.50 to 2.21 and <200 cells/µL, aRR = 3.26 (2.47 to 4.30)] and a low nadir CD4 [<200 cells/µL, aRR = 1.56 (1.37 to 1.79)] but not among PWH with normal CD4 [≥500 cells/µL, aRR = 1.14 (0.90 to 1.44)]. Higher incident HF risk was observed among PWH at all HIV RNA levels, with greater HF risk at higher HIV RNA levels. The excess HF risk associated with low CD4 (recent or nadir) and high HIV RNA was stronger among women than men (P interactions=0.05, 0.08, and 0.01, respectively)., Conclusions: Given the association of HIV severity with HF, optimizing HIV treatment and management may be important for HF prevention among PWH., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: End-stage liver disease (ESLD) is a leading cause of non-AIDS-related death among people with HIV (PWH). Factors that increase the progression of liver disease include comorbidities and HIV-specific factors, but we currently lack a tool to apply this evidence into clinical practice., Methods: We developed and validated a risk prediction model for ESLD among PWH who received care in 12 cohorts of the North American AIDS Cohort Collaboration on Research and Design between 2000 and 2016 and had fibrosis-4 index > 1.45. The first occurrence of ascites, variceal bleed, spontaneous bacterial peritonitis, or hepatic encephalopathy was verified by standardized medical record review. The Bayesian model averaging was used to select predictors among biomarkers and diagnoses and the Harrell C statistic to assess model discrimination., Results: Among 13,787 PWH in the training set, 82% were men and 54% were Black with a mean age of 48 years. Three hundred ninety ESLD events occurred over a mean 5.4 years. Among the ESLD cases, 52% had hepatitis C virus, 15% hepatitis B virus, and 31% alcohol use disorder. Twelve factors together predicted ESLD risk moderately well (C statistic 0.79, 95% confidence interval: 0.76 to 0.81): age, sex, race/ethnicity, chronic hepatitis B or C, and routinely collected laboratory values reflecting hepatic impairment (serum albumin, aspartate aminotransferase, total bilirubin, and platelets) and lipid metabolism (triglycerides, high-density lipoprotein, and total cholesterol). Our model performed well in the test set (C statistic 0.81, 95% confidence interval: 0.76 to 0.86)., Conclusion: This model of readily accessible clinical parameters predicted ESLD in a large diverse population of PWH., Competing Interests: E.R.C. has received research grants paid to UC Reagents from Gilead Sciences and Merck & Co., Inc., and has been on an advisory board for Gilead Sciences. M.K. reports grants for investigator-initiated studies from ViiV Healthcare, AbbVie, Merck, and Gilead Sciences and consulting fees from ViiV Healthcare, Merck, AbbVie, and Gilead Sciences. The remaining authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: People with HIV (PWH) have a higher hospitalization rate than the general population. The Veterans Aging Cohort Study (VACS) Index at study entry well predicts hospitalization in PWH, but it is unknown if the time-updated parameter improves hospitalization prediction. We assessed the association of parameterizations of the VACS Index 2.0 with the 5-year risk of hospitalization., Setting: PWH ≥30 years old with at least 12 months of antiretroviral therapy (ART) use and contributing hospitalization data from 2000 to 2016 in North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) were included. Three parameterizations of the VACS Index 2.0 were assessed and categorized by quartile: (1) "baseline" measurement at study entry; (2) time-updated measurements; and (3) cumulative scores calculated using the trapezoidal rule., Methods: Discrete-time proportional hazard models estimated the crude and adjusted associations (and 95% confidence intervals [CIs]) of the VACS Index parameterizations and all-cause hospitalizations. The Akaike information criterion (AIC) assessed the model fit with each of the VACS Index parameters., Results: Among 7289 patients, 1537 were hospitalized. Time-updated VACS Index fitted hospitalization best with a more distinct dose-response relationship [score <43: reference; score 43-55: aHR = 1.93 (95% CI: 1.66 to 2.23); score 55-68: aHR = 3.63 (95% CI: 3.12 to 4.23); score ≥68: aHR = 9.98 (95% CI: 8.52 to 11.69)] than study entry and cumulative VACS Index after adjusting for known risk factors., Conclusions: Time-updated VACS Index 2.0 had the strongest association with hospitalization and best fit to the data. Health care providers should consider using it when assessing hospitalization risk among PWH., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Studies suggest lower risk of breast cancer in women with HIV versus without HIV. These estimates may be biased by lower life expectancy and younger age distribution of women with HIV. Our analysis evaluated this bias and characterized secular trends in breast cancer among women with HIV initiating antiretroviral therapy. We hypothesized breast cancer risk would increase over time as mortality decreased., Setting: Women with HIV prescribed antiretroviral therapy in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) from 1997 through 2016., Methods: We estimated breast cancer hazard (cause-specific hazard ratios) and cumulative incidence accounting for competing risks (subdistribution hazard ratios) to assess changes in breast cancer risk over time. This was assessed overall (1997-2016) and within/across calendar periods. Analyses were adjusted for race/ethnicity and inverse probability weighted for cohort. Cumulative incidence was graphically assessed by calendar period and race/ethnicity., Results: We observed 11,587 women during 1997-2016, contributing 63 incident breast cancer diagnoses and 1,353 deaths [73,445 person-years (median follow-up = 4.5 years)]. Breast cancer cumulative incidence was 3.2% for 1997-2016. We observed no secular trends in breast cancer hazard or cumulative incidence. There were annual declines in the hazard and cumulative incidence of death (cause-specific hazard ratios and subdistribution hazard ratios: 0.89, 95% confidence interval: 0.87 to 0.91) which remained within and across calendar periods., Conclusions: These findings contradict the hypothesis of increasing breast cancer risk with declining mortality over time among women with HIV, suggesting limited impact of changing mortality on breast cancer risk. Additional inquiry is merited as survival improves among women with HIV., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Optimal management of noncommunicable diseases, including diabetes mellitus (DM), is crucially important as people with HIV (PWH) live longer with antiretroviral therapy. Our objective was to assess patient-level and clinic-level factors associated with achieving hemoglobin A1c (HbA1c) ≤7.0% among PWH and DM., Setting: The DC Cohort, an observational clinical cohort of PWH, followed from 2011 to 2019 at 12 sites in Washington, DC., Methods: Among PWH with diagnosed DM and elevated HbA1c (>7.0%), we examined the association between achieving HbA1c ≤7.0% and demographic and clinical factors, including time-updated medication data, and clinic-level factors related to services and structure. A multilevel marginal extended Cox regression model was generated to identify factors associated with time to HbA1c ≤7.0%., Results: Over half (52.3%) of 419 participants achieved HbA1c ≤7.0%. Individual-level factors associated with HbA1c ≤7.0% included a diagnosis of DM after enrollment and a longer time since HIV diagnosis [hazard ratio (HR) = 2.65 and 1.13, P < 0.05 for both]. Attending a clinic with an endocrinologist was associated with the outcome [adjusted HR (aHR) = 1.41 95% confidence interval (CI): (1.01 to 1.97)]. In addition, comparing clinics that treat everyone, refer everyone or have a mix of treating and referring, showed an association between attending a clinic that treats everyone [aHR = 1.52 95% CI: (1.21 to 1.90)] or a clinic that refers everyone [aHR = 2.24 95% CI: (1.63 to 3.07)] compared with clinics with a mix in achieving glycemic control., Conclusion: Multiple factors are associated with achieving glycemic control in an urban cohort of PWH. Determining if specific services or structures improve DM outcomes may improve health outcomes for PWH and DM.

Objective: To evaluate associations of mood, anxiety, stress-/trauma-related, and psychotic disorders, both treated and untreated, with duration of unsuppressed HIV viral load (VL) among persons living with HIV (PLWH)., Setting: The DC Cohort, an observational clinical cohort of PLWH followed from 2011 to 2018 at 14 sites in Washington, DC., Methods: Among PLWH ≥18 years old who received primary care at their HIV clinic, we determined in a time-updated manner whether participants had diagnoses and pharmacologic prescriptions for mood, anxiety, stress-/trauma-related, and/or psychotic disorders. Associations between psychiatric disorders/treatments and the proportion of subsequent days with VL ≥200 copies/mL were assessed using multivariable Poisson regression with generalized estimating equations., Results: Among 5904 participants (median age 51; 70% men; 82% Black), 45% had ≥1 psychiatric disorder, including 38% with mood disorders (50% treated), 18% with anxiety or stress-/trauma-related disorders (64% treated), and 4% with psychotic disorders (52% treated). Untreated major depressive disorder (adjusted rate ratio = 1.17; 95% confidence interval: 1.00 to 1.37), untreated other/unspecified depressive disorder (1.23; 1.01 to 1.49), untreated bipolar disorder (1.39; 1.15 to 1.69), and treated bipolar disorder (1.25; 1.02 to 1.53) (vs. no mood disorder) predicted more time with VL ≥200 copies/mL. Treated anxiety disorders (vs. no anxiety disorder) predicted less time (0.78; 0.62 to 0.99). Associations were weaker and nonsignificant for treated depressive disorders (vs. no mood disorder) and untreated anxiety disorders (vs. no anxiety disorder)., Conclusions: PLWH with depressive and bipolar disorders, particularly when untreated, spent more time with unsuppressed VL than PLWH without a mood disorder. Treatment of mood disorders may be important for promoting sustained viral suppression.

Background: Hepatitis B virus (HBV) infection is a leading cause of end-stage liver disease (ESLD) and hepatocellular carcinoma (HCC) in HIV. Factors contributing to the high rates of liver complications among HIV/HBV-coinfected individuals remain unknown., Setting: North American AIDS Cohort Collaboration on Research and Design., Methods: We performed a retrospective cohort study among HIV/HBV-coinfected patients in 10 US and Canadian cohorts of the North American AIDS Cohort Collaboration on Research and Design that validated ESLD (ascites, spontaneous bacterial peritonitis, variceal hemorrhage, and/or hepatic encephalopathy) and HCC diagnoses from 1996 to 2010. Multivariable Cox regression was used to examine adjusted hazard ratios [aHRs with 95% confidence interval (CIs)] of liver complications (first occurrence of ESLD or HCC) associated with hypothesized determinants and with increasing durations of HIV suppression (≤500 copies/mL)., Results: Among 3573 HIV/HBV patients with 13,790 person-years of follow-up, 111 liver complications occurred (incidence rate = 8.0 [95% CI: 6.6 to 9.7] events/1000 person-years). Rates of liver complication were increased with non-black/non-Hispanic race [aHR = 1.76 (1.13-2.74)], diabetes mellitus [aHR = 2.07 (1.20-3.57)], lower time-updated CD4 cell count [<200 cells/mm: aHR = 2.59 (1.36-4.91); 201-499 cells/mm: aHR = 1.75 (1.01-3.06) versus ≥500 cells/mm], heavy alcohol use [aHR = 1.58 (1.04-2.39)], and higher FIB-4 at start of follow-up [>3.25: aHR = 9.79 (5.73-16.74); 1.45-3.25: aHR = 3.20 (1.87-5.47) versus FIB-4 <1.45]. HIV suppression for ≥6 months was associated with lower liver complication rates compared with those with unsuppressed HIV [aHR = 0.56 (0.35-0.91)]., Conclusions: Non-black/non-Hispanic race, diabetes, lower CD4 cell count, heavy alcohol use, and advanced liver fibrosis were determinants of liver complications among HIV/HBV patients. Sustained HIV suppression should be a focus for HIV/HBV-coinfected patients to reduce the risks of ESLD/HCC.

Background: It is not known whether immune dysfunction is associated with increased risk of death after cancer diagnosis in persons with HIV (PWH). AIDS-defining illness (ADI) can signal significant immunosuppression. Our objective was to determine differences in cancer stage and mortality rates in PWH with and without history of ADI., Methods: PWH with anal, oropharynx, cervical, lung cancers, or Hodgkin lymphoma diagnoses from January 2000 to December 2009 in the North American AIDS Cohort Collaboration on Research and Design were included., Results: Among 81,865 PWH, 814 had diagnoses included in the study; 341 (39%) had a history of ADI at time of cancer diagnosis. For each cancer type, stage at diagnosis did not differ by ADI (P > 0.05). Mortality and survival estimates for cervical cancer were limited by n = 5 diagnoses. Adjusted mortality rate ratios showed a 30%-70% increase in mortality among those with ADI for all cancer diagnoses, although only lung cancer was statistically significant. Survival after lung cancer diagnosis was poorer in PWH with ADI vs. without (P = 0.0001); the probability of survival was also poorer in those with ADI at, or before other cancers although not statistically significant., Conclusions: PWH with a history of ADI at lung cancer diagnosis had higher mortality and poorer survival after diagnosis compared to those without. Although not statistically significant, the findings of increased mortality and decreased survival among those with ADI (vs. without) were consistent for all other cancers, suggesting the need for further investigations into the role of HIV-related immune suppression and cancer outcomes.

Background: Cutaneous melanoma incidence may be modestly elevated in people with HIV (PWH) vs. people without HIV. However, little is known about the relationship of immunosuppression, HIV replication, and antiretroviral therapy (ART) with melanoma risk., Methods: PWH of white race in the North American AIDS Cohort Collaboration on Research and Design were included. A standardized incidence ratio was calculated comparing risk with the white general population, standardizing by age, sex, and calendar period. Associations between melanoma incidence and current, lagged, and cumulative measures of CD4 count, HIV RNA level, and ART use were estimated with Cox regression, adjusting for established risk factors such as age and annual residential ultraviolet B (UVB) exposure., Results: Eighty melanomas were diagnosed among 33,934 white PWH (incidence = 40.75 per 100,000 person-years). Incidence was not elevated compared with the general population [standardized incidence ratio = 1.15, 95% confidence interval (95% CI) = 0.91 to 1.43]. Higher melanoma incidence was associated with older age [adjusted hazard ratio (aHR) per decade increase = 1.50, 95% CI = 1.20 to 1.89] and higher UVB exposure (aHR for exposure ≥35 vs. <35 mW/m = 1.62, 95% CI = 0.99 to 2.65). Current, lagged, and cumulative CD4 and HIV RNA were not associated with melanoma incidence. Melanoma incidence was higher among people ART-treated for a larger proportion of time in the previous 720 days (aHR per 10% increase = 1.16, 95% CI = 1.03 to 1.30)., Conclusions: These results suggest that HIV-induced immune dysfunction does not influence melanoma development. The association between ART and melanoma risk may be due to increased skin surveillance among PWH engaged in clinical care. Associations with age and UVB confirmed those established in the general population.

Background: There 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., Methods: Incident 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., Results: Eight 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 (<200 cells/mm) CD4 counts, and a history of AIDS. The risk of the combined MI outcome was greater for persons who used ABC in the previous 6 months [aHR = 1.84 (1.17-2.91)]; and persisted for T1MI (aHR = 1.62 [1.01]) and T2MI [aHR = 2.11 (1.08-4.29)]. FRS did not modify the effect of ABC on MI (P = 0.14) and inclusion of FRS in the MSM did not diminish the effect of recent ABC use on the combined outcome., Conclusions: Recent ABC use was associated with MI after adjustment for known risk factors and for FRS. However, screening for T1MI risks may not identify all or even most persons at risk of ABC use-associated MIs.

Background: Kaposi sarcoma (KS) remains common among HIV-infected persons. To better understand KS etiology and to help target prevention efforts, we comprehensively examined a variety of CD4 T-cell count and HIV-1 RNA viral load (VL) measures, as well as antiretroviral therapy (ART) use, to determine independent predictors of KS risk., Setting: North American AIDS Cohort Collaboration on Research and Design., Methods: We followed HIV-infected persons during 1996-2009 from 18 cohorts. We used time-updated Cox regression to model relationships between KS risk and recent, lagged, trajectory, and cumulative CD4 count or VL measures, as well as ART use. We used Akaike's information criterion and global P values to derive a final model., Results: In separate models, the relationship between each measure and KS risk was highly significant (P < 0.0001). Our final mutually adjusted model included recent CD4 count [hazard ratio (HR) for <50 vs. ≥500 cells/μL = 12.4; 95% confidence interval (CI): 6.5 to 23.8], recent VL (HR for ≥100,000 vs. ≤500 copies/mL = 3.8; 95% CI: 2.0 to 7.3), and cumulative (time-weighted mean) VL (HR for ≥100,000 vs. ≤500 copies/mL = 2.5; 95% CI: 1.0 to 5.9). Each P-trend was <0.0001. After adjusting for these measures, we did not detect an independent association between ART use and KS risk., Conclusions: Our results suggested a multifactorial etiology for KS, with early and late phases of development. The cumulative VL effect suggested that controlling HIV replication promptly after HIV diagnosis is important for KS prevention. We observed no evidence for direct anti-KS activity of ART, independent of CD4 count and VL.

Background: Prior studies found overweight or obese HIV-infected individuals had greater early CD4 cell recovery on antiretroviral therapy (ART), but the results have been inconsistent. We assessed the longitudinal relationship between body mass index (BMI) and CD4 cell recovery on ART in a large, multisite cohort to identify potential physiologic links between adiposity and CD4 cell expansion., Methods: We modeled the relationship of time-updated BMI with CD4 count in patients starting ART from 17 North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) cohorts. The primary analysis used a linear mixed effects model incorporating up to 13 years of data per patient and adjusted for age, sex, race, ART regimen, baseline CD4 count and other covariates. Sensitivity analyses limited the cohort to patients with sustained viral suppression or censored at virologic failure., Results: Fourteen thousand eighty-four HIV-infected individuals initiating ART contributed data between 1998 and 2010. Time-updated BMI was significantly associated with CD4 cell recovery over time (P < 0.001). After 5 years of ART, the mean CD4 count at a BMI of 30 kg/m was 22% higher than at a BMI of 22 kg/m (606 vs. 498 cells per microliter) and 34% higher at a BMI of 40 kg/m (665 vs. 498 cells per microliter). Results were similar in the sensitivity analyses., Discussion: Higher BMI is associated with long-term advantages in immune recovery on ART. Although it is unclear if this impacts health outcomes, including balancing the negative health effects of obesity, elucidating the underlying mechanism could identify therapies for patients with suboptimal immune reconstitution.

Background: It is unknown if a survival gap remains between HIV-infected and HIV-uninfected individuals with access to care., Methods: We conducted a cohort study within Kaiser Permanente California during 1996-2011, using abridged life tables to estimate the expected years of life remaining ("life expectancy") at age 20., Results: Among 24,768 HIV-infected and 257,600 HIV-uninfected individuals, there were 2229 and 4970 deaths, with mortality rates of 1827 and 326 per 100,000 person-years, respectively. In 1996-1997, life expectancies at age 20 for HIV-infected and HIV-uninfected individuals were 19.1 and 63.4 years, respectively, corresponding with a gap of 44.3 years (95% confidence interval: 38.4 to 50.2). Life expectancy at age 20 for HIV-infected individuals increased to 47.1 years in 2008 and 53.1 years by 2011, narrowing the gap to 11.8 years (8.9-14.8 years) in 2011. In 2008-2011, life expectancies at age 20 for HIV-infected individuals ranged from a low of 45.8 years for blacks and 46.0 years for those with a history of injection drug use to a high of 52.2 years for Hispanics. HIV-infected individuals who initiated antiretroviral therapy with CD4 ≥500 cells per microliter had a life expectancy at age 20 of 54.5 years in 2008-2011, narrowing the gap relative to HIV-uninfected individuals to 7.9 years (5.1-10.6 years). For these HIV-infected individuals, the gap narrowed further in subgroups with no history of hepatitis B or C infection, smoking, drug/alcohol abuse, or any of these risk factors., Conclusions: Even with early treatment and access to care, an 8-year gap in life expectancy remains for HIV-infected compared with HIV-uninfected individuals.

Background: Evidence is conflicting about the association of abacavir use and cardiovascular disease (CVD) among HIV-infected individuals. Previous studies may have been biased by the preferential initiation or continuation of abacavir in patients with renal dysfunction., Methods: We conducted a cohort study in Kaiser Permanente California during 1998-2011, following HIV-infected adults initiating antiretroviral therapy until the earliest of CVD (ie, coronary heart disease or ischemic stroke), health plan disenrollment, death, or end of study. We used inverse-probability weighting to fit marginal structural models to estimate hazard ratios (HRs) for CVD comparing regimens with and without abacavir. Propensity score models included demographics, HIV-specific factors, and CVD risk factors, including alcohol/drug use, smoking, overweight/obesity, diabetes, lipid-lowering and hypertension therapy, and renal dysfunction (ie, estimated glomerular filtration rate <60 mL·min·1.73 m)., Results: Among 8154 subjects, 178 had ≥1 CVD event, with 24/704 (3.4%) in the abacavir group and 154/7450 (2.1%) in the group initiating regimens without abacavir. Abacavir users had more renal dysfunction at antiretroviral therapy initiation (7.0% vs. 3.3%, P < 0.001). Compared with patients initiating regimens without abacavir, abacavir users had a 2.2-fold higher risk of CVD in intention-to-treat analysis [HR 2.2, 95% confidence interval (CI): 1.4 to 3.5], a 2.7-fold higher risk when remaining on their initial regimens for ≥1 year (HR 2.7, 95% CI: 1.5 to 5.0), and a 2.1-fold higher risk in per-protocol analysis (HR 2.1, 95% CI: 0.9 to 5.0)., Conclusions: Abacavir was associated with an over 2-fold increased risk of CVD, which was not explained by renal dysfunction or other CVD risk factors.

Background: Retention in care is important for all HIV-infected persons and is strongly associated with initiation of antiretroviral therapy and viral suppression. However, it is unclear how retention in care and age interact to affect viral suppression. We evaluated whether the association between retention and viral suppression differed by age at entry into care., Methods: Cross-sectional analysis (2006-2010) involving 17,044 HIV-infected adults in 14 clinical cohorts across the United States and Canada. Patients contributed 1 year of data during their first full-calendar year of clinical observation. Poisson regression examined associations between retention measures [US National HIV/AIDS Strategy (NHAS), US Department of Health and Human Services (DHHS), 6-month gap, and 3-month visit constancy] and viral suppression (HIV RNA ≤200 copies/mL) by age group: 18-29 years, 30-39 years, 40-49 years, 50-59 years, and 60 years or older., Results: Overall, 89% of patients were retained in care using the NHAS measure, 74% with the DHHS indicator, 85% did not have a 6-month gap, and 62% had visits in 3-4 quarters of the year; 54% achieved viral suppression. For each retention measure, the association with viral suppression was significant for only the younger age groups (18-29 and 30-39 years): 18-29 years [adjusted prevalence ratio (APR) = 1.33, 95% confidence interval (CI): 1.03 to 1.70]; 30-39 years (APR = 1.23, 95% CI: 1.01 to 1.49); 40-49 years (APR = 1.06, 95% CI: 0.90 to 1.22); 50-59 (APR = 0.92, 95% CI: 0.75 to 1.13); ≥60 years (APR = 0.99, 95% CI: 0.63 to 1.56) using the NHAS measure as a representative example., Conclusions: These results have important implications for improving viral control among younger adults, emphasizing the crucial role retention in care plays in supporting viral suppression in this population.

Background: We investigated whether the reported lower incidence of prostate cancer in HIV-positive men is a result of confounding factors or reduced screening., Methods: We conducted a cohort study of 17,424 HIV-positive and 182,799 HIV-negative men enrolled in Kaiser Permanente (KP). Subjects were followed from the first KP enrollment after January 01, 1996 for KP Northern California (KPNC) and January 01, 2000 for KP Southern California until the earliest of prostate cancer diagnosis, loss to follow-up, or December 31, 2007. Poisson regression was used to compare cancer rates by HIV status adjusting for age, race, smoking, alcohol/drug abuse, overweight/obesity, and diabetes. For the KPNC subset, we analyzed additional available data by HIV status on testosterone deficiency, and on prostate-specific antigen (PSA) tests as a proxy for cancer screening., Results: The prostate cancer incidence rate was 102/100,000 person-years in HIV-positive men (n = 74 cases) and 131/100,000 person-years in HIV-negative men (n = 1195 cases), with an adjusted rate ratio of 0.73 (95% confidence interval: 0.57 to 0.92; P = 0.008). The reduced risk among HIV-positive men was greater for higher-stage cancers, which are less likely to be biased by screening differences than lower-stage cancers. In the KPNC subset, more HIV-positive (90.8%) than HIV-negative men (86.2%) received a PSA test by age 55 (P < 0.001). Decreased risk for HIV-positive men remained when examined only among those with a previous PSA test, and with adjustment for testosterone deficiency (rate ratio = 0.55; 95% confidence interval: 0.39 to 0.80; P = 0.001)., Conclusions: Prostate cancer incidence rates are lower in HIV-positive compared with HIV-negative men, which is not explained by screening differences or the risk factors evaluated.

Background: We sought to clarify the association of HIV infection and immunodeficiency on myocardial infarction (MI) risk., Methods: We conducted a cohort study from 1996 to 2009 of HIV-positive (HIV) and demographically matched HIV-negative (HIV) Kaiser Permanente California health plan members. Rate ratios (RRs) were obtained from Poisson regression models comparing MI incidence rates between HIV (overall and stratified by recent and nadir CD4 count, and recent HIV RNA levels) and HIV subjects, adjusting for age, sex, calendar era, race/ethnicity, census-based socioeconomic status, smoking, alcohol/drug abuse, overweight/obesity, diabetes, hypertension, and lipid-lowering therapy. Among HIV subjects, we also evaluated the independent association of CD4, HIV RNA, and antiretroviral therapy (ART) use., Results: The study population included 22,081 HIV and 230,069 HIV subjects. The crude MI incidence rate per 100,000 person-years was 283 and 165 for HIV and HIV subjects, respectively, with an adjusted RR of 1.4 [95% confidence interval (CI): 1.3 to 1.6]. Compared with HIV subjects (reference), MI rates were similar for HIV subjects with recent CD4 ≥500 cells per microliter (RR = 1.18; 95% CI: 0.96 to 1.45) and those with nadir CD4 ≥500 cells per microliter (RR = 0.85; 95% CI: 0.55 to 1.33). Among HIV subjects, nadir CD4 was the only HIV-specific factor associated with MIs (RR per 100 cells = 0.88; 95% CI: 0.81 to 0.96), whereas recent CD4 and HIV RNA, prior ART use, and duration of protease inhibitors and nonnucleoside reverse transcriptase inhibitors were not associated with MIs., Conclusion: HIV subjects with recent or nadir CD4 ≥500 cells per microliter had similar MI rates compared with HIV subjects. Lower nadir CD4, in particular, seems to be independently associated with MIs. These results strengthen recommendations for earlier ART initiation.

Background: By supplementing an index composed of HIV biomarkers and age (restricted index) with measures of organ injury, the Veterans Aging Cohort Study (VACS) index more completely reflects risk of mortality. We compare the accuracy of the VACS and restricted indices (1) among subjects outside the Veterans Affairs Healthcare System, (2) more than 1-5 years of prior exposure to antiretroviral therapy (ART), and (3) within important patient subgroups., Methods: We used data from 13 cohorts in the North American AIDS Cohort Collaboration (n = 10, 835) limiting analyses to HIV-infected subjects with at least 12 months exposure to ART. Variables included demographic, laboratory (CD4 count, HIV-1 RNA, hemoglobin, platelets, aspartate and alanine transaminase, creatinine, and hepatitis C status), and survival. We used C-statistics and net reclassification improvement (NRI) to test discrimination varying prior ART exposure from 1 to 5 years. We then combined Veterans Affairs Healthcare System (n = 5066) and North American AIDS Cohort Collaboration data, fit a parametric survival model, and compared predicted to observed mortality by cohort, gender, age, race, and HIV-1 RNA level., Results: Mean follow-up was 3.3 years (655 deaths). Compared with the restricted index, the VACS index showed greater discrimination (C-statistics: 0.77 vs. 0.74; NRI: 12%; P < 0.0001). NRI was highest among those with HIV-1 RNA <500 copies per milliliter (25%) and age ≥50 years (20%). Predictions were similar to observed mortality among all subgroups., Conclusions: VACS index scores discriminate risk and translate into accurate mortality estimates over 1-5 years of exposure to ART and for diverse patient subgroups from North American.

Background: Limited data exists regarding the effect of chronic HIV infection on the liver. We sought to characterize the hepatic risks of HIV infection, immunodeficiency, and cumulative use of antiretroviral therapy (ART)., Methods: Adult HIV infected and 10:1 age-matched and sex-matched HIV-uninfected individuals were followed for incident hepatic dysfunction or hepatic dysfunction-related death. Multivariable Poisson regression models were used to obtain incident rate ratios, adjusting for multiple hepatic risk factors including alcohol/drug abuse, hepatitis B and C, and diabetes., Results: We identified 20,775 HIV-infected and 215,158 HIV-uninfected individuals. HIV-infected individuals had a significantly greater overall risk compared with HIV-uninfected individuals of both hepatic dysfunction and hepatic dysfunction-related death. The highest risk was seen in patients with low CD4 cell counts not on ART [adjusted rate ratio of hepatic dysfunction-related death 59.4; (95% confidence interval: 39.3 to 89.7), P < 0.001; hepatic dysfunction, adjusted rate ratio 15.7 (95% confidence interval: 11.4 to 21.6), P < 0.001]. In an HIV-infected only model, factors that increased risk included low CD4 cell count, high HIV RNA level, alcohol/drug abuse, hepatitis B or C coinfection, and diabetes. Longer cumulative exposure to ART did not increase risk, regardless of therapy class., Conclusions: HIV-infected individuals have a higher risk of hepatic dysfunction and hepatic dysfunction-related death compared with HIV-uninfected individuals, even with adjustment for known hepatic risk factors. Hepatic outcomes were associated with lower CD4+ T-cell counts but not with longer cumulative ART exposure. These findings provide indirect evidence supporting early use of ART to reduce the risk for hepatic-related complications.

Objective: We seek to determine the optimized multidisciplinary care team (MDCT) composition for antiretroviral therapy (ART) adherence., Methods: We analyzed all new regimen starts (n = 10,801; 7071 ART naive, 3730 ART experienced) among HIV-positive patients in Kaiser Permanente California from 1996 to 2006. We measured 12-month adherence to ART (pharmacy refill methodology) and medical center-specific patient exposure to HIV/infectious disease specialist (reference group), non-HIV primary care provider, clinical pharmacist, nurse case manager, non-nurse care coordinator, dietician, social worker/benefits coordinator, health educator, and mental health worker. We used recursive partitioning to ascertain potential MDCT compositions associated with maximal mean ART adherence. We then employed mixed linear regression with clustering by provider and medical center (adjusting for ART experience, age, gender, race/ethnicity, HIV risk, hepatitis C virus coinfection, ART regimen class, and calendar year) to test which potential MDCT combination identified had statistically significant association with ART adherence., Results: We found maximal increase in adherence with pharmacist plus coordinator plus primary care provider combination (8.1% ART adherence difference compared with reference; 95% confidence interval: 2.7% to 13.5%). Other MDCT teams with significantly (P < 0.05) improved adherence compared with specialist only were nurse plus social worker with primary care provider (7.5%; 5.4% to 9.7%), specialist plus mental health worker (6.5%; 2.6% to 10.4%), pharmacist plus social worker plus primary care provider (5.7%; 4.1% to 7.4%), and pharmacist plus primary care provider (3.3%; 0.8% to 5.8%). Among these MDCTs, there were no significant differences in mean adherence, odds of maximal viral control, or CD4+ changes at 12 months (except pharmacist plus primary care provider)., Conclusions: Various MDCTs were associated with improved adherence, including ones that did not include the HIV specialist but included primary care plus other health professionals. These findings have application to the HIV care team design.

Objectives: To determine the impact of depression on highly active antiretroviral therapy (HAART) adherence and clinical measures and investigate if selective serotonin reuptake inhibitors (SSRIs) improve these measures., Design: Retrospective cohort study., Methods: In 2 large health maintenance organizations, we measured the effects of depression (with and without SSRI use) on adherence and changes in viral and immunologic control among HIV-infected patients starting a new HAART regimen. HAART adherence, HIV RNA levels, and changes in CD4 T-cell counts through 12 months were measured., Results: A total of 3359 patients were evaluated; 42% had a depression diagnosis, and 15% used SSRIs during HAART. Depression without SSRI use was associated with significantly decreased odds of achieving > or =90% adherence to HAART (odds ratio [OR] = 0.81, 95% confidence interval [CI]: 0.70 to 0.98; P = 0.03). Depression was associated with significantly lower odds of an HIV RNA level <500 copies/mL (OR = 0.77, 95% CI: 0.62 to 0.95; P = 0.02). Depressed patients compliant with SSRI medication (>80% adherence to SSRI) had HAART adherence and viral control statistically similar to nondepressed HIV-infected patients taking HAART. Comparing depressed with nondepressed HIV-infected patients, CD4 T-cell responses were statistically similar; among depressed patients, those compliant with SSRI had statistically greater increases in CD4 cell responses., Conclusions: Depression significantly worsens HAART adherence and HIV viral control. Compliant SSRI use is associated with improved HIV adherence and laboratory parameters.

Objective: To determine the association of clinical pharmacists with health outcomes and utilization measures among HIV-infected patients., Methods: Observational study of 1571 HIV-infected patients prescribed their initial highly active antiretroviral therapy (HAART) regimen in clinics with and without a clinical pharmacist. Outcomes analyzed were changes in plasma HIV RNA level, CD4 T-cell counts, and service utilization (hospital days, emergency department visits, and office visits) over 24 months based on exposure to a clinical pharmacist., Results: Patients exposed to a clinical pharmacist tended to be more likely to achieve an HIV RNA level <500 copies/mL at 12 months (adjusted odds ratio [OR] = 2.01, 95% confidence interval [CI]: 0.92 to 4.37). At 24 months, however, results depended on the provider panel size; the ORs for panel sizes < or =50 and >50 HIV-infected patients were 1.67 (95% CI: 0.60 to 4.62) and 0.97 (95% CI: 0.39 to 2.41), respectively. CD4 T-cell counts were modestly but nonsignificantly higher for the patients exposed to a clinical pharmacist. Utilization also depended on the provider panel size; pharmacist exposure was associated with 64% (95% CI: 30% to 108%) and 9% (95% CI: -11% to 33%) increases in total hospital days for panel sizes < or =50 and >50 HIV-infected patients, respectively. Pharmacist exposure was also associated with a 19% (95% CI: -13% to -24%) decrease in office visits for panel sizes < or =50 HIV-infected patients, with minimal effect for larger panel sizes., Conclusion: Clinical pharmacists seem to contribute to lower office visit rates in antiretroviral-naive patients initiating HAART.