Amy Justice | Yale University School of Medicine (original) (raw)

Papers by Amy Justice

Journal of Acquired Immune Deficiency Syndromes, Feb 1, 2013

Background-By supplementing an index composed of HIV biomarkers and age (Restricted Index) with m... more 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 Healthcare System (VA), 2) over 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 (NA-ACCORD, 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 statistic and net reclassification improvement (NRI) to test discrimination varying prior ART exposure from 1-5 years. We then combined VA (n=5,066) and NA-ACCORD 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 statistic: 0.77 vs. 0.74; NRI 12%; p<0.0001). NRI was highest among those with HIV-1 RNA<500 copies/ml (25%) and age ≥50 years (20%). Predictions were similar to observed mortality among all subgroups. Conclusion-VACS Index scores discriminate risk and translate into accurate mortality estimates over 1-5 years of exposures to ART and for diverse patient subgroups from North American

Clinical Infectious Diseases, Jan 23, 2014

We estimated US Department of Health and Human Services (DHHS)-approved human immunodeficiency vi... more We estimated US Department of Health and Human Services (DHHS)-approved human immunodeficiency virus (HIV) indicators. Among patients, 71% were retained in care, 82% were prescribed treatment, and 78% had HIV RNA ≤200 copies/mL; younger adults, women, blacks, and injection drug users had poorer outcomes. Interventions are needed to reduce retention-and treatment-related disparities.

Carolina Digital Repository (University of North Carolina at Chapel Hill), 2015

Background. Human immunodeficiency virus (HIV)-infected adults, particularly those of black race,... more Background. Human immunodeficiency virus (HIV)-infected adults, particularly those of black race, are at high-risk for end-stage renal disease (ESRD), but contributing factors are evolving. We hypothesized that improvements in HIV treatment have led to declines in risk of ESRD, particularly among HIV-infected blacks. Methods. Using data from the North American AIDS Cohort Collaboration for Research and Design from January 2000 to December 2009, we validated 286 incident ESRD cases using abstracted medical evidence of dialysis (lasting >6 months) or renal transplant. A total of 38 354 HIV-infected adults aged 18-80 years contributed 159 825 person-years (PYs). Age-and sex-standardized incidence ratios (SIRs) were estimated by race. Poisson regression was used to identify predictors of ESRD. Results. HIV-infected ESRD cases were more likely to be of black race, have diabetes mellitus or hypertension, inject drugs, and/or have a prior AIDS-defining illness. The overall SIR was 3.2 (95% confidence interval [CI], 2.8-3.6) but was significantly higher among black patients (4.5 [95% CI, 3.9-5.2]). ESRD incidence declined from 532 to 303 per 100 000 PYs and 138 to 34 per 100 000 PYs over the time period for blacks and nonblacks, respectively, coincident with notable increases in both the prevalence of viral suppression and the prevalence of ESRD risk factors including diabetes mellitus, hypertension, and hepatitis C virus coinfection. Conclusions. The risk of ESRD remains high among HIV-infected individuals in care but is declining with improvements in virologic suppression. HIV-infected black persons continue to comprise the majority of cases, as a result of higher viral loads, comorbidities, and genetic susceptibility.

Carolina Digital Repository (University of North Carolina at Chapel Hill), 2013

The Lancet HIV, Apr 1, 2019

Declaration of interests KNA serves on the scientific advisory board of TrioHealth, Inc.. MJG has... more Declaration of interests KNA serves on the scientific advisory board of TrioHealth, Inc.. MJG has served as an ad hoc member of Canadian HIV Advisory Boards of Merck, Gilead and ViiV. RDM has previously consulted for Medscape. MJS has received grants from Gilead and, formerly, Merck. The remaining authors have no conflicts of interest to disclose.

Purpose: FIB-4 is an established marker of liver fibrosis and cirrhosis, calculated from platelet... more Purpose: FIB-4 is an established marker of liver fibrosis and cirrhosis, calculated from platelet count, alanine transaminase, aspartate transaminase, and age. We previously found baseline FIB-4 to be strongly associated with hepatocellular carcinoma (HCC) risk among HIV-infected (HIV+) patients in the US; a similar finding was reported among persons who consume alcohol or are chronic hepatitis B virus (HBV) carriers in South Korea. Longitudinal associations between FIB-4 and HCC risk have not yet been explored. We aimed to expand our prior investigation by including uninfected patients, using time-updated FIB-4, and testing for multiplicative interaction between HIV status and FIB-4 in the prediction of HCC risk. We hypothesized that the relationship between FIB-4 and HCC risk would differ by HIV status. Methods: We tested this hypothesis in the Veterans Aging Cohort Study, an open cohort that enrolls HIV+ veterans when they begin HIV care in the Veterans Health Administration and matches two uninfected patients by age, sex, race/ethnicity, and clinical site. We used proportional hazards regression models with time-varying covariates to calculate hazard ratios (HR) and 95% confidence intervals (CI) for FIB-4, adjusted for HCC risk factors (age, sex, race, hepatitis C virus (HCV) infection, HBV infection, smoking, alcohol, BMI, and diabetes). We used the counting process to create time-updated FIB-4 intervals and examined one-, three-, and five-year lagged FIB-4. We identified incident HCC cases from the VA Central Cancer Registry and determined hepatitis C virus and hepatitis B virus status from laboratory results. We defined low (3.25) as previously established. Results: Between 2000 and 2012, among 37,158 HIV+ subjects, 202 developed HCC. Among 78,339 uninfected subjects, 207 developed HCC. There was a significant multiplicative interaction between HIV status and one-year lagged FIB-4 (interaction p = 0.0015). High FIB-4 was a stronger predictor of HCC in the uninfected than in HIV+. Among uninfected, the adjusted HR was 6.9 (95% CI: 3.4, 12.5) for intermediate FIB-4 and 40.0 (95% CI: 22.3, 71.8) for high FIB-4 compared to uninfected with low FIB-4. Among HIV+, with the same reference group (uninfected with low FIB-4), the adjusted HR was 2.1 (95% CI: 1.0, 4.4) for low FIB-4, 6.4 (95% CI: 3.5, 11.7) for intermediate FIB-4, and 23.7 (95% CI: 13.1, 42.9) for high FIB-4. There was no interaction between FIB-4 and HCV status (p = 0.92). Results were qualitatively similar using a three- or five-year lag. Conclusions: Calculated from routine, non-invasive laboratory tests, FIB-4 is a strong, independent HCC risk factor in both HIV+ and uninfected subjects after adjustment for other HCC risk factors. FiB-4 appears to be a stronger risk factor in uninfected than in HIV+. Citation Format: Lesley S. Park, Janet P. Tate, Vincent Lo Re, Adeel A. Butt, Cynthia Gibert, Matthew Bidwell Goetz, Sheldon T. Brown, Joseph Lim, David Rimland, Jennifer S. Lee, Amy C. Justice, Robert Dubrow. Multiplicative interaction between HIV infection status and FIB-4 in prediction of hepatocellular carcinoma risk. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4308.

Pneumonia, Jul 25, 2020

Background: Cohort studies identifying the incidence, complications and co-morbidities associated... more Background: Cohort studies identifying the incidence, complications and co-morbidities associated with community acquired pneumonia (CAP) are largely based on administrative datasets and rely on International Classification of Diseases (ICD) codes; however, the reliability of ICD codes for hospital admissions for CAP in people with HIV (PWH) has not been systematically assessed. Methods: We used data from the Veterans Aging Cohort Study survey sample (N = 6824; 3410 PWH and 3414 uninfected) to validate the use of electronic health records (EHR) data to identify CAP hospitalizations when compared to chart review and to compare the performance in PWH vs. uninfected patients. We used different EHR algorithms that included a broad set of CAP ICD-9 codes, a set restricted to bacterial and viral CAP codes, and algorithms that included pharmacy data and/or other ICD-9 diagnoses frequently associated with CAP. We also compared microbiologic workup and etiologic diagnosis by HIV status among those with CAP. Results: Five hundred forty-nine patients were identified as having an ICD-9 code compatible with a CAP diagnosis (13% of PWH and 4% of the uninfected, p < 0.01). The EHR algorithm with the best overall positive predictive value (82%) was obtained by using the restricted set of ICD-9 codes (480-487) in primary position or secondary only to selected codes as primary (HIV disease, respiratory failure, sepsis or bacteremia) with the addition of EHR pharmacy data; this algorithm yielded PPVs of 83% in PWH and 73% in uninfected (P = 0.1) groups. Adding aspiration pneumonia (ICD-9 code 507) to any of the ICD-9 code/pharmacy combinations increased the number of cases but decreased the overall PPV. Allowing COPD exacerbation in the primary position improved the PPV among the uninfected group only (to 76%). More PWH than uninfected patients underwent microbiologic evaluation or had respiratory samples submitted. Conclusions: ICD-9 code-based algorithms perform similarly to identify CAP in PLWH and uninfected individuals. Adding antimicrobial use data and allowing as primary diagnoses ICD-9 codes frequently used in patients with CAP improved the performance of the algorithms in both groups of patients. The algorithms consistently performed better among PWH.

$Research paper thumbnail of FIB-4 stage of liver fibrosis is associated with incident heart failure with preserved, but not reduced, ejection fraction among people with and without HIV or hepatitis C$

Progress in Cardiovascular Diseases, Mar 1, 2020

Background-Liver fibrosis, is independently associated with incident heart failure (HF). Investig... more Background-Liver fibrosis, is independently associated with incident heart failure (HF). Investigating the association between liver fibrosis and type of HF, specifically HF with reduced ejection fraction (EF; HFrEF) or HF with preserved ejection fraction (HFpEF), may provide mechanistic insight into this association. We sought to determine the association between liver fibrosis score (FIB-4) and type of HF, and to assess whether HIV or hepatitis C status modified this association. Methods-We included patients alive on or after 4/1/2003 from the Veterans Aging Cohort Study. We followed patients without prevalent cardiovascular disease until their first HF event, death, last clinic visit, or 9/30/2015. We defined liver fibrosis as: likely advanced fibrosis (FIB-4 > 3.25), indeterminate (FIB-4 range 1.45-3.25), unlikely advanced fibrosis (FIB-4 < 1.45). Primary outcomes were HFrEF and HFpEF (defined using ICD-9 diagnoses for HF, and EF extracted from electronic medical records using natural language processing). Cox proportional hazards models were adjusted for potential confounders and used to estimate hazard ratios (HR). Results-Among 108,708 predominantly male (96%) participants mean age was 49 years. Likely advanced fibrosis was present in 4% at baseline and was associated with an increased risk of HFpEF [HR (95% confidence interval)] [1.70 (1.3-2.3)]; and non-significantly with HFrEF [1.20 (0.9-1.7)]. These associations were not modified by HIV or hepatitis C status. Conclusion-Likely advanced fibrosis was independently associated with incident HFpEF but not HFrEF. This suggests that risk factors and/or mechanisms for liver fibrosis may have greater overlap with those for HFpEF than HFrEF.

Journal of Acquired Immune Deficiency Syndromes, Oct 1, 2016

to study design, data interpretation, and discussion and reviewed and edited the manuscript. A.J,... more to study design, data interpretation, and discussion and reviewed and edited the manuscript. A.J, is the guarantor of this work and, as such, had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Carolina Digital Repository (University of North Carolina at Chapel Hill), Dec 15, 2010

We assessed CD4 count at initial presentation for HIV care among ≥50-year-olds from 1997-2007 in ... more We assessed CD4 count at initial presentation for HIV care among ≥50-year-olds from 1997-2007 in 13 US and Canadian clinical cohorts and compared to <50-year-olds. 44,491 HIV-infected individuals in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) were included in our study. Trends in mean CD4 count (measured as cells/mm 3) and 95% confidence intervals ([,]) were determined using linear regression stratified by age category and adjusted for gender, race/ethnicity, HIV transmission risk and cohort. From 1997-2007, the proportion of individuals presenting for HIV care who were ≥50-years-old increased from 17% to 27% (p-value < 0.01). The median CD4 count among ≥50 year-olds was consistently lower than younger adults. The interaction of age group and calendar year was significant (p-value <0.01) with both age groups experiencing modest annual improvements over time (< 50-year-olds: 5[4 , 6] cells/mm 3 ; ≥50-year-olds: 7[5 , 9] cells/mm 3), after adjusting for sex, race/ethnicity, HIV transmission risk group and cohort; however, increases in the two groups were similar after 2000. A greater proportion of older individuals had an AIDS-defining diagnosis at, or within three months prior to, first presentation for HIV care compared to younger individuals (13% vs. 10%, respectively). Due to the increasing proportion, consistently lower CD4 counts, and more advanced HIV disease in adults ≥50-year-old at first presentation for HIV care, renewed HIV testing efforts are needed.

Clinical Infectious Diseases, Aug 18, 2016

Six HIV care metrics (baseline and time-updated HIV-1 RNA, viremia copy-years, time-updated CD4, ... more Six HIV care metrics (baseline and time-updated HIV-1 RNA, viremia copy-years, time-updated CD4, time-updated VACS Index, and VACS Index score-years) predicted AMI and mortality among HIV infected individuals. Time-updated VACS Index provided the best prediction for both AMI and mortality.

Journal of Acquired Immune Deficiency Syndromes, Dec 15, 2020

Background:Hepatocellular carcinoma (HCC) may develop in the absence of cirrhosis in HIV, and det... more Background:Hepatocellular carcinoma (HCC) may develop in the absence of cirrhosis in HIV, and determining how often this occurs can provide insights into mechanisms of carcinogenesis. Studies evaluating the prevalence of cirrhosis in the setting of HCC among people living with HIV (PLWH) often rely on non-invasive markers, such as the Fibrosis-4 Index for Hepatic Fibrosis (FIB-4). However, the accuracy of FIB-4 for cirrhosis in the setting of HCC has not been determined among PLWH.Methods:We conducted a cross-sectional study among PLWH in the Veterans Aging Cohort Study with VA cancer registry-confirmed HCC diagnosed between 1999 and 2015. FIB-4 was calculated using the age, alanine aminotransferase, aspartate aminotransferase, and platelet count obtained closest, but within one year prior, to HCC diagnosis. Medical records were reviewed within one year prior to HCC diagnosis to determine cirrhosis status. We evaluated the area under the receiver-operating characteristic curve (AUROC) and performance characteristics of FIB-4 for confirmed cirrhosisResults:Incident HCC was diagnosed in 302 PLWH. After medical record review, 203 (67.2%, 95% [confidence interval] CI, 61.6–72.5%) had evidence of cirrhosis. FIB-4 identified patients with cirrhosis with an AUROC of 0.67 (95% CI, 0.60–0.73). FIB-4 scores >5.0 had a positive predictive value >80% and specificity of >77%, negative predictive value <41% and sensitivity of <45%.Conclusion:The accuracy of FIB-4 for cirrhosis in the setting of HIV and HCC is modest and may result in misclassification of cirrhosis in this population.

European Respiratory Journal

BackgroundDexamethasone decreases mortality in coronavirus disease 2019 (COVID-19) patients on in... more BackgroundDexamethasone decreases mortality in coronavirus disease 2019 (COVID-19) patients on intensive respiratory support (IRS) but is of uncertain benefit if less severely ill. We determined whether early (within 48 h) dexamethasone was associated with mortality in patients hospitalised with COVID-19 not on IRS.MethodsWe included patients admitted to US Veterans Affairs hospitals between 7 June 2020 and 31 May 2021 within 14 days after a positive test for severe acute respiratory syndrome coronavirus 2. Exclusions included recent prior corticosteroids and IRS within 48 h. We used inverse probability of treatment weighting (IPTW) to balance exposed and unexposed groups, and Cox proportional hazards models to determine 90-day all-cause mortality.ResultsOf 19 973 total patients (95% men, median age 71 years, 27% black), 15 404 (77%) were without IRS within 48 h. Of these, 3514 out of 9450 (34%) patients on no oxygen received dexamethasone and 1042 (11%) died; 4472 out of 5954 (75%)...

JAIDS Journal of Acquired Immune Deficiency Syndromes, 2017

Although sleep disturbance has been observed at all stages of HIV infection, 1-4 the nature of th... more Although sleep disturbance has been observed at all stages of HIV infection, 1-4 the nature of the association between HIV and sleep disturbance has not been rigorously evaluated in the current treatment era. We explored the longitudinal associations between HIV status and self-reported occurrence or severity of sleep disturbance, with adjustment for demographics, comorbidities, and polypharmacy. We used the Veterans Aging Cohort Study (VACS), a longitudinal, prospective observational study of HIV infected and uninfected Veterans enrolled at eight Veterans Health Administration (VHA) medical centers: Atlanta, Baltimore, Brooklyn and Manhattan, Bronx, Houston, Los Angeles, Pittsburgh, and Washington DC. HIV infected Veterans were matched one to one with uninfected Veterans by age, race/ethnicity, site of clinical care, and sex. 5 Data for this analysis included electronic health-record (EHR) data and self-report questionnaires completed by participants at enrollment (baseline) (June 2002 through August 2012) and through six years of follow-up.

HIV Medicine, 2016

ObjectivesCertain prescribed opioids have immunosuppressive properties, yet their impact on clini... more ObjectivesCertain prescribed opioids have immunosuppressive properties, yet their impact on clinically relevant outcomes, including antiretroviral therapy (ART) response among HIV‐infected patients, remains understudied.MethodsUsing the Veterans Aging Cohort Study data, we conducted a longitudinal analysis of 4358 HIV‐infected patients initiating ART between 2002 and 2010 and then followed them for 24 months. The primary independent variable was prescribed opioid duration, categorized using pharmacy data as none prescribed, short‐term (< 90 days) and long‐term (≥ 90 days). Outcomes included CD4 cell count over time. Analyses adjusted for demographics, comorbid conditions, ART type and year of initiation, and overall disease severity [ascertained with the Veterans Aging Cohort Study (VACS) Index]. Sensitivity analyses examined whether effects varied according to baseline CD4 cell count, achievement of viral load suppression, and opioid properties (i.e. dose and known immunosuppres...

JAIDS Journal of Acquired Immune Deficiency Syndromes, 2016

Background-FRAX® is a validated, computer-based clinical fracture risk calculator that estimates ... more Background-FRAX® is a validated, computer-based clinical fracture risk calculator that estimates 10-year risk of major osteoporotic (clinical spine, forearm, hip or shoulder) fracture, and hip fracture alone. It is widely used for decision-making in fracture prevention, but may underestimate risk in HIV-infected individuals. Some experts recommend considering HIV a cause of secondary osteoporosis when calculating FRAX in HIV-infected individuals. Methods-From the Veterans Aging Study Virtual Cohort (VACS-VC), we included 24451 HIV-infected and uninfected 50-70 year old men with complete data in year 2000 to approximate all but two factors (i.e. history of secondary osteoporosis and parental hip fracture) for modified-FRAX calculation without bone density and 10-year observational data for incident fragility fracture. Accuracy of the modified-FRAX calculation was compared by observed/estimated (O/E) ratios of fracture by HIV status. Results-Accuracy of modified-FRAX was less for HIV-infected (O/E=1.62, 95%CI: 1.45, 1.81) than uninfected men (O/E=1.29, 95%CI: 1.19, 1.40), but improved when HIV was included as a cause of secondary osteoporosis (O/E=1.20, 95%CI: 1.08, 1.34). However, only 3-6% of men

HIV Medicine, 2015

Objectives-Outcomes of community-acquired pneumonia (CAP) among HIV-infected older adults are unc... more Objectives-Outcomes of community-acquired pneumonia (CAP) among HIV-infected older adults are unclear. Methods-Associations between HIV infection and three CAP outcomes (30-day mortality, readmission within 30 days post-discharge, and hospital length of stay [LOS]) were examined in the Veterans Aging Cohort Study (VACS) of male Veterans, age ≥ 50 years, hospitalized for CAP from 10/1/2002 through 08/31/2010. Associations between the VACS Index and CAP outcomes were assessed in multivariable models. Results-Among 117 557 Veterans (36 922 HIV-infected and 80 635 uninfected), 1203 met our eligibility criteria. The 30-day mortality rate was 5.3%, the mean LOS was 7.3 days, and 13.2% were readmitted within 30 days of discharge. In unadjusted analyses, there were no significant differences between HIV-infected and uninfected participants regarding the three CAP outcomes (P > 0.2). A higher VACS Index was associated with increased 30-day mortality, readmission, and LOS in both HIV-infected and uninfected groups. Generic organ system components of the VACS Index were associated with adverse CAP outcomes; HIV-specific components were not. Among HIV-infected participants, those not on antiretroviral therapy (ART) had a higher 30-day mortality

D105. LUNG COMPLICATIONS OF CHRONIC HIV INFECTION: PREVALENCE, PATHOGENESIS, AND PHYSIOLOGY, 2011

Page 1. / Poster D105 LUNG COMPLICATIONS OF CHRONIC HIV INFECTION: PREVALENCE, PATHOGENESIS, AND ... more Page 1. / Poster D105 LUNG COMPLICATIONS OF CHRONIC HIV INFECTION: PREVALENCE, PATHOGENESIS, AND PHYSIOLOGY Discussion Session / Wednesday, May 18/2:00 PM-4:30 PM / Korbel Ballroom 1C-1D (Lower Level), Colorado Convention Center ...

C104. HIV ASSOCIATED LUNG DISEASE INCLUDING PNEUMOCYSTIS, 2010

B23. OUTCOMES, HEALTH SERVICES AND PATIENT-CENTERED RESEARCH IN THE INTENSIVE CARE UNIT, 2012