Lesley Park

All Publications

• Trends in Hepatocellular Carcinoma Incidence and Risk Among Persons With HIV in the US and Canada, 1996-2015. JAMA network open Sun, J., Althoff, K. N., Jing, Y., Horberg, M. A., Buchacz, K., Gill, M. J., Justice, A. C., Rabkin, C. S., Goedert, J. J., Sigel, K., Cachay, E., Park, L., Lim, J. K., Kim, H. N., Lo Re, V. 3., Moore, R., Sterling, T., Peters, M. G., Achenbach, C. J., Silverberg, M., Thorne, J. E., Mayor, A. M., Crane, H. M., Kitahata, M. M., Klein, M., Kirk, G. D., North American AIDS Cohort Collaboration on Research and Design of IeDEA 2021; 4 (2): e2037512

  Abstract

  Importance: People with HIV (PWH) are often coinfected with hepatitis B virus (HBV) and/or hepatitis C virus (HCV), leading to increased risk of developing hepatocellular carcinoma (HCC), but few cohort studies have had sufficient power to describe the trends of HCC incidence and risk among PWH in the combination antiretroviral therapy (cART) era.Objective: To determine the temporal trends of HCC incidence rates (IRs) and to compare rates by risk factors among PWH in the cART era.Design, Setting, and Participants: This cohort study used data from the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) study, which was conducted between 1996 and 2015. NA-ACCORD pooled individual-level data from 22 HIV clinical and interval cohorts of PWH in the US and Canada. PWH aged 18 years or older with available CD4 cell counts and HIV RNA data were enrolled. Data analyses were completed in March 2020.Exposures: HBV infection was defined as detection of either HBV surface antigen, HBV e antigen, or HBV DNA in serum or plasma any time during observation. HCV infection was defined by detection of anti-HCV seropositivity, HCV RNA, or detectable genotype in serum or plasma at any time under observation.Main Outcomes and Measures: HCC diagnoses were identified on the basis of review of medical records or cancer registry linkage.Results: Of 109?283 PWH with 723?441 person-years of follow-up, the median (interquartile range) age at baseline was 43 (36-51) years, 93?017 (85.1%) were male, 44?752 (40.9%) were White, 44?322 (40.6%) were Black, 21?343 (19.5%) had HCV coinfection, 6348 (5.8%) had HBV coinfection, and 2082 (1.9%) had triple infection; 451 individuals received a diagnosis of HCC by 2015. Between the early (1996-2000) and modern (2006-2015) cART eras, the crude HCC IR increased from 0.28 to 0.75 case per 1000 person-years. HCC IRs remained constant among HIV-monoinfected persons or those coinfected with HBV, but from 1996 to 2015, IRs increased among PWH coinfected with HCV (from 0.34 cases/1000 person-years in 1996 to 2.39 cases/1000 person-years in 2015) or those with triple infection (from 0.65 cases/1000 person-years in 1996 to 4.49 cases/1000 person-years in 2015). Recent HIV RNA levels greater than or equal to 500 copies/mL (IR ratio, 1.8; 95% CI, 1.4-2.4) and CD4 cell counts less than or equal to 500 cells/muL (IR ratio, 1.3; 95% CI, 1.0-1.6) were associated with higher HCC risk in the modern cART era. People who injected drugs had higher HCC risk compared with men who had sex with men (IR ratio, 2.0; 95% CI, 1.3-2.9), adjusted for HBV-HCV coinfection.Conclusions and Relevance: HCC rates among PWH increased significantly over time from 1996 to 2015. PWH coinfected with viral hepatitis, those with higher HIV RNA levels or lower CD4 cell counts, and those who inject drugs had higher HCC risk.

  View details for DOI 10.1001/jamanetworkopen.2020.37512

  View details for PubMedID 33595662

• Brief Report: Accuracy of FIB-4 for Cirrhosis in People Living With HIV and Hepatocellular Carcinoma. Journal of acquired immune deficiency syndromes (1999) Torgersen, J., Kallan, M. J., Carbonari, D. M., Park, L. S., Mehta, R. L., D'Addeo, K., Tate, J. P., Lim, J. K., Goetz, M. B., Rodriguez-Barradas, M. C., Brau, N., Brown, S. T., Taddei, T. H., Justice, A. C., Lo Re, V. 3. 2020; 85 (5): 530?34

  Abstract

  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 noninvasive 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 to, but within 1 year before, HCC diagnosis. Medical records were reviewed within 1 year before HCC diagnosis to determine the cirrhosis status. We evaluated the area under the receiver-operating characteristic curve and performance characteristics of FIB-4 for confirmed cirrhosis.RESULTS: Incident HCC was diagnosed in 302 PLWH. After medical record review, 203 (67.2%, 95% confidence interval: 61.6% to 72.5%) had evidence of cirrhosis. FIB-4 identified patients with cirrhosis with an area under the receiver-operating characteristic curve of 0.67 (95% confidence interval: 0.60 to 0.73). FIB-4 scores >5.0 had a positive predictive value >80% and specificity of >77%, negative predictive value of <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.

  View details for DOI 10.1097/QAI.0000000000002510

  View details for PubMedID 33185999

• RISK OF SEVERE ACUTE LIVER INJURY AMONG INITIATORS OF POTENTIALLY HEPATOTOXIC DRUGS Mezochow, A., Torgersen, J., Newcomb, C. W., Carbonari, D., Hennessy, S., Park, L. S., Mehta, R., Tate, J. P., Taddei, T. H., Justice, A. C., Lo Re, V. WILEY. 2020: 87A?88A

  View details for Web of Science ID 000574027000120

• A HISTOLOGICAL RESOURCE TO EXAMINE HIV AND AGING MECHANISMS FOR HEPATOCELLULAR CARCINOMA Park, L. S., Zhang, X., Nalbantoglu, I., Kidwai-Khan, F., Mehta, R., Carbonari, D., Torgersen, J., Lo Re, V., Justice, A. C., Taddei, T. H. WILEY. 2020: 627A

  View details for Web of Science ID 000574027002166

• Risk of acute liver injury with protease inhibitor-based antiviral therapy for hepatitis C Torgersen, J., Newcomb, C. W., Carbonari, D. M., Rentsch, C. T., Park, L. S., Mehta, R., D'Addeo, K., Taddei, T., Justice, A. C., Lo Re, V. WILEY. 2020: 614?15

  View details for Web of Science ID 000577640502092

• Patterns of COVID-19 testing and mortality by race and ethnicity among United States veterans: A nationwide cohort study. PLoS medicine Rentsch, C. T., Kidwai-Khan, F., Tate, J. P., Park, L. S., King, J. T., Skanderson, M., Hauser, R. G., Schultze, A., Jarvis, C. I., Holodniy, M., Lo Re, V., Akgün, K. M., Crothers, K., Taddei, T. H., Freiberg, M. S., Justice, A. C. 2020; 17 (9): e1003379

  Abstract

  There is growing concern that racial and ethnic minority communities around the world are experiencing a disproportionate burden of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19). We investigated racial and ethnic disparities in patterns of COVID-19 testing (i.e., who received testing and who tested positive) and subsequent mortality in the largest integrated healthcare system in the United States.This retrospective cohort study included 5,834,543 individuals receiving care in the US Department of Veterans Affairs; most (91%) were men, 74% were non-Hispanic White (White), 19% were non-Hispanic Black (Black), and 7% were Hispanic. We evaluated associations between race/ethnicity and receipt of COVID-19 testing, a positive test result, and 30-day mortality, with multivariable adjustment for a wide range of demographic and clinical characteristics including comorbid conditions, health behaviors, medication history, site of care, and urban versus rural residence. Between February 8 and July 22, 2020, 254,595 individuals were tested for COVID-19, of whom 16,317 tested positive and 1,057 died. Black individuals were more likely to be tested (rate per 1,000 individuals: 60.0, 95% CI 59.6-60.5) than Hispanic (52.7, 95% CI 52.1-53.4) and White individuals (38.6, 95% CI 38.4-38.7). While individuals from minority backgrounds were more likely to test positive (Black versus White: odds ratio [OR] 1.93, 95% CI 1.85-2.01, p < 0.001; Hispanic versus White: OR 1.84, 95% CI 1.74-1.94, p < 0.001), 30-day mortality did not differ by race/ethnicity (Black versus White: OR 0.97, 95% CI 0.80-1.17, p = 0.74; Hispanic versus White: OR 0.99, 95% CI 0.73-1.34, p = 0.94). The disparity between Black and White individuals in testing positive for COVID-19 was stronger in the Midwest (OR 2.66, 95% CI 2.41-2.95, p < 0.001) than the West (OR 1.24, 95% CI 1.11-1.39, p < 0.001). The disparity in testing positive for COVID-19 between Hispanic and White individuals was consistent across region, calendar time, and outbreak pattern. Study limitations include underrepresentation of women and a lack of detailed information on social determinants of health.In this nationwide study, we found that Black and Hispanic individuals are experiencing an excess burden of SARS-CoV-2 infection not entirely explained by underlying medical conditions or where they live or receive care. There is an urgent need to proactively tailor strategies to contain and prevent further outbreaks in racial and ethnic minority communities.

  View details for DOI 10.1371/journal.pmed.1003379

  View details for PubMedID 32960880

• Trajectories of Self-Reported Opioid Use Among Patients With HIV Engaged in Care: Results From a National Cohort Study. Journal of acquired immune deficiency syndromes (1999) Edelman, E. J., Li, Y., Barry, D., Brennan Braden, J., Crystal, S., Kerns, R. D., Gaither, J. R., Gordon, K. S., Manhapra, A., Merlin, J. S., Moore, B. A., Oldfield, B. J., Park, L. S., Rentsch, C. T., Skanderson, M., Williams, E. C., Justice, A. C., Tate, J. P., Becker, W. C., Marshall, B. D. 2020; 84 (1): 26?36

  Abstract

  No prior studies have characterized long-term patterns of opioid use regardless of source or reason for use among patients with HIV (PWH). We sought to identify trajectories of self-reported opioid use and their correlates among a national sample of PWH engaged in care.Veterans Aging Cohort Study, a prospective cohort including PWH receiving care at 8 US Veterans Health Administration (VA) sites.Between 2002 and 2018, we assessed past year opioid use frequency based on self-reported "prescription painkillers" and/or heroin use at baseline and follow-up. We used group-based trajectory models to identify opioid use trajectories and multinomial logistic regression to determine baseline factors independently associated with escalating opioid use compared to stable, infrequent use.Among 3702 PWH, we identified 4 opioid use trajectories: (1) no lifetime use (25%); (2) stable, infrequent use (58%); (3) escalating use (7%); and (4) de-escalating use (11%). In bivariate analysis, anxiety; pain interference; prescribed opioids, benzodiazepines and gabapentinoids; and marijuana use were associated with escalating opioid group membership compared to stable, infrequent use. In multivariable analysis, illness severity, pain interference, receipt of prescribed benzodiazepine medications, and marijuana use were associated with escalating opioid group membership compared to stable, infrequent use.Among PWH engaged in VA care, 1 in 15 reported escalating opioid use. Future research is needed to understand the impact of psychoactive medications and marijuana use on opioid use and whether enhanced uptake of evidence-based treatment of pain and psychiatric symptoms can prevent escalating use among PWH.

  View details for DOI 10.1097/QAI.0000000000002310

  View details for PubMedID 32267658

• Covid-19 by Race and Ethnicity: A National Cohort Study of 6 Million United States Veterans. medRxiv : the preprint server for health sciences Rentsch, C. T., Kidwai-Khan, F., Tate, J. P., Park, L. S., King, J. T., Skanderson, M., Hauser, R. G., Schultze, A., Jarvis, C. I., Holodniy, M., Re, V. L., Akgün, K. M., Crothers, K., Taddei, T. H., Freiberg, M. S., Justice, A. C. 2020

  Abstract

  There is growing concern that racial and ethnic minority communities around the world are experiencing a disproportionate burden of morbidity and mortality from symptomatic SARS-Cov-2 infection or coronavirus disease 2019 (Covid-19). Most studies investigating racial and ethnic disparities to date have focused on hospitalized patients or have not characterized who received testing or those who tested positive for Covid-19.To compare patterns of testing and test results for coronavirus 2019 (Covid-19) and subsequent mortality by race and ethnicity in the largest integrated healthcare system in the United States.Retrospective cohort study.United States Department of Veterans Affairs (VA).5,834,543 individuals in care, among whom 62,098 were tested and 5,630 tested positive for Covid-19 between February 8 and May 4, 2020. Exposures: Self-reported race/ethnicity.We evaluated associations between race/ethnicity and receipt of Covid-19 testing, a positive test result, and 30-day mortality, accounting for a wide range of demographic and clinical risk factors including comorbid conditions, site of care, and urban versus rural residence.Among all individuals in care, 74% were non-Hispanic white (white), 19% non-Hispanic black (black), and 7% Hispanic. Compared with white individuals, black and Hispanic individuals were more likely to be tested for Covid-19 (tests per 1000: white=9.0, [95% CI 8.9 to 9.1]; black=16.4, [16.2 to 16.7]; and Hispanic=12.2, [11.9 to 12.5]). While individuals from minority backgrounds were more likely to test positive (black vs white: OR 1.96, 95% CI 1.81 to 2.12; Hispanic vs white: OR 1.73, 95% CI 1.53 to 1.96), 30-day mortality did not differ by race/ethnicity (black vs white: OR 0.93, 95% CI 0.64 to 1.33; Hispanic vs white: OR 1.07, 95% CI 0.61 to 1.87).Black and Hispanic individuals are experiencing an excess burden of Covid-19 not entirely explained by underlying medical conditions or where they live or receive care. While there was no observed difference in mortality by race or ethnicity, our findings may underestimate risk in the broader US population as health disparities tend to be reduced in VA.

  View details for DOI 10.1101/2020.05.12.20099135

  View details for PubMedID 32511524

  View details for PubMedCentralID PMC7273292

• Statin exposure and risk of cancer in people with and without HIV infection. AIDS (London, England) Bedimo, R. J., Park, L. S., Shebl, F., Sigel, K., Rentsch, C. T., Crothers, K., Rodriguez-Barradas, M. C., Goetz, M. B., Butt, A. A., Brown, S. T., Gibert, C., Justice, A. C., Tate, J. P. 2020

  Abstract

  To determine whether statin exposure is associated with decreased cancer and mortality risk among persons with HIV (PWH) and uninfected persons. Statins appear to have immunomodulatory and anti-inflammatory effects and may reduce cancer risk, particularly among PWH as they experience chronic inflammation and immune activation.Propensity score matched cohort of statin-exposed and unexposed patients from 2002-2017 in the Veterans Aging Cohort Study (VACS), a large cohort with cancer registry linkage and detailed pharmacy data.We calculated Cox regression hazard ratios (HRs) and 95% confidence intervals (CI) associated with statin use for all cancers, microbial cancers (associated with bacterial or oncovirus coinfection), non-microbial cancers, and mortality.The propensity score-matched sample (N?=?47,940) included 23,970 statin initiators (31% PWH). Incident cancers were diagnosed in 1,160 PWH and 2,116 uninfected patients. Death was reported in 1,667 (7.0%) statin-exposed, and 2,215 (9.2%) unexposed patients. Statin use was associated with 24% decreased risk of microbial associated cancers (HR 0.76; 95% CI 0.69-0.85), but was not associated with non-microbial cancer risk (HR 1.00; 95% CI 0.92-1.09). Statin use was associated with 33% lower risk of death overall (HR 0.67; 95% CI 0.63-0.72). Results were similar in analyses stratified by HIV status, except for non-Hodgkin lymphoma where statin use was associated with reduced risk (HR 0.56; 95% CI 0.38-0.83) for PWH, but not for uninfected (p-interaction?=?0.012).In both PWH and uninfected, statin exposure was associated with lower risk of microbial, but not non-microbial cancer incidence, and with decreased mortality.

  View details for DOI 10.1097/QAD.0000000000002748

  View details for PubMedID 33181533

• Development and validation of a 30-day mortality index based on pre-existing medical administrative data from 13,323 COVID-19 patients: The Veterans Health Administration COVID-19 (VACO) Index. PloS one King, J. T., Yoon, J. S., Rentsch, C. T., Tate, J. P., Park, L. S., Kidwai-Khan, F., Skanderson, M., Hauser, R. G., Jacobson, D. A., Erdos, J., Cho, K., Ramoni, R., Gagnon, D. R., Justice, A. C. 2020; 15 (11): e0241825

  Abstract

  BACKGROUND: Available COVID-19 mortality indices are limited to acute inpatient data. Using nationwide medical administrative data available prior to SARS-CoV-2 infection from the US Veterans Health Administration (VA), we developed the VA COVID-19 (VACO) 30-day mortality index and validated the index in two independent, prospective samples.METHODS AND FINDINGS: We reviewed SARS-CoV-2 testing results within the VA between February 8 and August 18, 2020. The sample was split into a development cohort (test positive between March 2 and April 15, 2020), an early validation cohort (test positive between April 16 and May 18, 2020), and a late validation cohort (test positive between May 19 and July 19, 2020). Our logistic regression model in the development cohort considered demographics (age, sex, race/ethnicity), and pre-existing medical conditions and the Charlson Comorbidity Index (CCI) derived from ICD-10 diagnosis codes. Weights were fixed to create the VACO Index that was then validated by comparing area under receiver operating characteristic curves (AUC) in the early and late validation cohorts and among important validation cohort subgroups defined by sex, race/ethnicity, and geographic region. We also evaluated calibration curves and the range of predictions generated within age categories. 13,323 individuals tested positive for SARS-CoV-2 (median age: 63 years; 91% male; 42% non-Hispanic Black). We observed 480/3,681 (13%) deaths in development, 253/2,151 (12%) deaths in the early validation cohort, and 403/7,491 (5%) deaths in the late validation cohort. Age, multimorbidity described with CCI, and a history of myocardial infarction or peripheral vascular disease were independently associated with mortality-no other individual comorbid diagnosis provided additional information. The VACO Index discriminated mortality in development (AUC = 0.79, 95% CI: 0.77-0.81), and in early (AUC = 0.81 95% CI: 0.78-0.83) and late (AUC = 0.84, 95% CI: 0.78-0.86) validation. The VACO Index allows personalized estimates of 30-day mortality after COVID-19 infection. For example, among those aged 60-64 years, overall mortality was estimated at 9% (95% CI: 6-11%). The Index further discriminated risk in this age stratum from 4% (95% CI: 3-7%) to 21% (95% CI: 12-31%), depending on sex and comorbid disease.CONCLUSION: Prior to infection, demographics and comorbid conditions can discriminate COVID-19 mortality risk overall and within age strata. The VACO Index reproducibly identified individuals at substantial risk of COVID-19 mortality who might consider continuing social distancing, despite relaxed state and local guidelines.

  View details for DOI 10.1371/journal.pone.0241825

  View details for PubMedID 33175863

• HIV RNA, CD4+ Percentage, and Risk of Hepatocellular Carcinoma by Cirrhosis Status. Journal of the National Cancer Institute Torgersen, J., Kallan, M. J., Carbonari, D. M., Park, L. S., Mehta, R. L., D'Addeo, K., Tate, J. P., Lim, J. K., Goetz, M. B., Rodriguez-Barradas, M. C., Gibert, C. L., Brau, N., Brown, S. T., Roy, J. A., Taddei, T. H., Justice, A. C., Re, V. L. 2019

  Abstract

  BACKGROUND: Despite increasing incidence of hepatocellular carcinoma (HCC) among HIV-infected patients, it remains unclear if HIV-related factors contribute to development of HCC. We examined if higher or prolonged HIV viremia and lower CD4+ cell percentage were associated with HCC.METHODS: We conducted a cohort study of HIV-infected individuals who had HIV RNA, CD4+, and CD8+ cell counts and percentages assessed in the Veterans Aging Cohort Study (1999-2015). HCC was ascertained using Veterans Health Administration cancer registries and electronic records. Cox regression was used to determine hazard ratios (HR, 95% confidence interval [CI]) of HCC associated with higher current HIV RNA, longer duration of detectable HIV viremia (?500 copies/mL), and current CD4+ cell percentage <14%, adjusting for traditional HCC risk factors. Analyses were stratified by previously validated diagnoses of cirrhosis prior to start of follow-up.RESULTS: Among 35,659 HIV-infected patients, 302 (0.8%) developed HCC over 281,441 person-years (incidence rate, 107.3/100,000 person-years). Among patients without baseline cirrhosis, higher HIV RNA (HR=1.25 [95%CI=1.12-1.40] per 1.0 log10 copies/mL) and ?12 months of detectable HIV (HR=1.47 [95%CI=1.02-2.11]) were independently associated with higher risk of HCC. CD4+ percentage <14% was not associated with HCC in any model. Hepatitis C coinfection was a statistically significant predictor of HCC regardless of baseline cirrhosis status.CONCLUSION: Among HIV-infected patients without baseline cirrhosis, higher HIV RNA and longer duration of HIV viremia increased risk of HCC, independent of traditional HCC risk factors. This is the strongest evidence to date that HIV viremia contributes to risk of HCC in this group.

  View details for DOI 10.1093/jnci/djz214

  View details for PubMedID 31687755

• HIV and cancer in the Veterans Health Administration System. Seminars in oncology Sigel, K., Park, L., Justice, A. 2019

  Abstract

  Cancer is a leading cause of death for people with HIV (PWH). The Veterans Healthcare System (VA) is the largest single institutional provider of HIV care in the United States. Cancer among Veterans with HIV is major issue and clinical research has expanded significantly during the antiretroviral therapy (ART) era providing numerous insights regarding cancer incidence, risk factors, prevention, treatment and outcomes for this unique group of patients. This work has been greatly facilitated by the availability of national VA data sources. Notably, patterns of cancer incidence have changed for Veterans with HIV during the ART era; non-AIDS defining malignancies now are the most common tumors. Despite better HIV control in the ART era, immunosuppression measured by low CD4 counts and HIV viremia have been associated with increased cancer risk. Cancer outcomes for Veterans with HIV may now be similar to uninfected Veterans, but information on outcomes and cancer treatment patterns remains limited, requiring further study to help inform prevention and treatment strategies.

  View details for DOI 10.1053/j.seminoncol.2019.09.007

  View details for PubMedID 31703932

• Differences in Pathology, Staging, and Treatment Between HIV+ and Uninfected Patients with Microscopically Confirmed Hepatocellular Carcinoma. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology Torgersen, J., Taddei, T. H., Park, L. S., Carbonari, D. M., Kallan, M. J., Mitchell Richards, K., Zhang, X., Jhala, D., Brau, N., Homer, R., D'Addeo, K., Mehta, R., Skanderson, M., Kidwai-Khan, F., Justice, A. C., Lo Re, V. 2019

  Abstract

  BACKGROUND: The incidence of hepatocellular carcinoma (HCC) is substantially higher among HIV-infected (HIV+) than uninfected persons. It remains unclear if HCC in the setting of HIV infection is morphologically distinct or more aggressive.METHODS: We evaluated differences in tumor pathology in a cohort of HIV+ and uninfected patients with microscopically confirmed HCC in the Veterans Aging Cohort Study from 2000-2015. We reviewed pathology reports and medical records to determine Barcelona Clinic Liver Cancer stage (BCLC), HCC treatment, and survival by HIV status. Multivariable Cox regression was used to determine the hazard ratio (HR [95% confidence interval]) of death associated with HIV infection after microscopic confirmation.RESULTS: Among 873 patients with HCC (399 HIV+), 140 HIV+ and 178 uninfected persons underwent liver tissue sampling and had microscopically confirmed HCC. There were no differences in histologic features of the tumor between HIV+ and uninfected patients, including tumor differentiation (well differentiated, 19% versus 28%, p=0.16) and lymphovascular invasion (6% versus 7%, p=0.17) or presence of advanced hepatic fibrosis (40% versus 39%, p=0.90). There were no differences in BCLC stage (p=0.06) or treatment (p=0.29) by HIV status. After adjustment for risk factors, risk of death was higher among HIV-infected than uninfected patients (HR, 1.37 [1.02-1.85]).CONCLUSIONS: We found no differences in HCC tumor characteristics or background hepatic parenchyma by HIV status, yet HIV was associated with poorer survival. Of note, pathology reports often omitted these characteristics.IMPACT: Systematic evaluation of HCC pathology by HIV status is needed to understand tumor characteristics associated with improved survival.

  View details for DOI 10.1158/1055-9965.EPI-19-0503

  View details for PubMedID 31575557

• Short-term outcomes for lung cancer resection surgery in HIV infection AIDS Sigel, K. M., Stone, K., Wisnivesky, J. P., Park, L. S., Kong, C., Silverberg, M. J., Brown, S., Goetz, M., Rodriguez-Barradas, M. C., Gibert, C., Shebl, F., Bedimo, R., Wadia, R., King, J., Crother, K. 2019; 33 (8): 1353?60

  View details for DOI 10.1097/QAD.0000000000002200

  View details for Web of Science ID 000480702500009

• Short-term outcomes for lung cancer resection surgery in HIV infection. AIDS (London, England) Sigel, K. M., Stone, K., Wisnivesky, J. P., Park, L. S., Kong, C. Y., Silverberg, M. J., Brown, S., Goetz, M., Rodriguez-Barradas, M. C., Gibert, C., Shebl, F., Bedimo, R., Wadia, R., King, J. J., Crothers, K. 2019

  Abstract

  OBJECTIVE: Lung cancer is the leading cause of cancer death in people living with HIV (PWH). Surgical resection is a key component of potentially curative treatment regimens for early-stage lung cancers, but its safety is unclear in the setting of HIV. From a national cohort, we assessed potential differences in the risk of major lung cancer surgery complications by HIV status.DESIGN: We linked clinical and cancer data from the Veterans Aging Cohort Study (VACS) and Veterans Affairs Corporate Data Warehouse to outcomes from the Veterans Affairs Surgical Quality Improvement Program (VASQIP) and identified 8371 patients (137 PWH, 8234 uninfected) who underwent lung cancer surgeries between 2000 and 2016.METHODS: We compared rates of 15 major short-term surgical complications by HIV status.RESULTS: Use of surgical resection for early-stage lung cancer did not differ by HIV status. Lung cancer surgery postoperative (30-day) mortality was 2.0% for PWH and did not differ by HIV status (P=0.9). Pneumonia was the most common complication for both PWH and uninfected veterans, but did not differ significantly in prevalence between groups (11.0% for PWH versus 9.4%; P=0.5). The frequency of complications did not differ by HIV status for any complication (all P>0.3). There were no significant predictors of postoperative complications for PWH.CONCLUSIONS: In a national antiretroviral-era cohort of lung cancer patients undergoing surgical lung resection, short-term outcomes after surgery did not differ significantly by HIV status. Concerns regarding short-term surgical complications should have limited influence on treatment decisions for PWH with lung cancer.

  View details for PubMedID 30889013

• Association of immunosuppression and HIV viraemia with non-Hodgkin lymphoma risk overall and by subtype in people living with HIV in Canada and the USA: a multicentre cohort study. The lancet. HIV Hernandez-Ramirez, R. U., Qin, L., Lin, H., Leyden, W., Neugebauer, R. S., Althoff, K. N., Achenbach, C. J., Hessol, N. A., D'Souza, G., Gebo, K. A., Gill, M. J., Grover, S., Horberg, M. A., Li, J., Mathews, W. C., Mayor, A. M., Park, L. S., Rabkin, C. S., Salters, K., Justice, A. C., Moore, R. D., Engels, E. A., Silverberg, M. J., Dubrow, R., North American AIDS Cohort Collaboration on Research and Design of the International Epidemiologic Databases to Evaluate AIDS, Betts, A., Brooks, J. T., Freeman, A. M., Van Rompaey, S. E., Burchell, A., Yip, B., You, B., Hogan, B., Grasso, C., Hogg, R. S., Benson, C. A., Drozd, D. R., Sterling, T. R., Haas, D., Humes, E., Crane, H. M., Willig, J., Eron, J. J., Martin, J. N., Saag, M. S., Jing, J., Zhang, J., Lindsay, J., Hunter-Mellado, R. F., Deeks, S. G., Zhu, J., Montaner, J. S., McReynolds, J., Gabler, K., Buchacz, K., Rodriguez, B., Thorne, J. E., Margolick, J. B., Anastos, K., Jacobson, L. P., Klein, M. B., Kroch, A., Morton, L., Turner, M., Fiellin, D., Gange, S. J., Mugavero, M. J., Harrigan, P. R., Rebeiro, P., Bosch, R. J., Kirk, G. D., Mayer, K. H., McKaig, R. G., Coburn, S., Napravnik, S., Kitahata, M. M., Lober, W. B., Lee, J. S. 2019

  Abstract

  BACKGROUND: Research is needed to better understand relations between immunosuppression and HIV viraemia and risk for non-Hodgkin lymphoma, a common cancer in people living with HIV. We aimed to identify key CD4 count and HIV RNA (viral load) predictors of risk for non-Hodgkin lymphoma, overall and by subtype.METHODS: We studied people living with HIV during 1996-2014 from 21 Canadian and US cohorts participating in the North American AIDS Cohort Collaboration on Research and Design. To determine key independent predictors of risk for non-Hodgkin lymphoma, we assessed associations with time-updated recent, past, cumulative, and nadir or peak measures of CD4 count and viral load, using demographics-adjusted, cohort-stratified Cox models, and we compared models using Akaike's information criterion.FINDINGS: Of 102?131 people living with HIV during the study period, 712 people developed non-Hodgkin lymphoma. The key independent predictors of risk for overall non-Hodgkin lymphoma were recent CD4 count (ie, lagged by 6 months; <50 cells per muL vs ?500 cells per muL, hazard ratio [HR] 3·2, 95% CI 2·2-4·7) and average viral load during a 3-year window lagged by 6 months (a cumulative measure; ?100?000 copies per mL vs ?500 copies per mL, HR 9·6, 95% CI 6·5-14·0). These measures were also the key predictors of risk for diffuse large B-cell lymphoma (recent CD4 count <50 cells per muL vs ?500 cells per muL, HR 2·4, 95% CI 1·4-4·2; average viral load ?100?000 copies per mL vs ?500 copies per mL, HR 7·5, 95% CI 4·5-12·7). However, recent CD4 count was the sole key predictor of risk for CNS non-Hodgkin lymphoma (<50 cells per muL vs ?500 cells per muL, HR 426·3, 95% CI 58·1-3126·4), and proportion of time viral load was greater than 500 copies per mL during the 3-year window (a cumulative measure) was the sole key predictor for Burkitt lymphoma (100% vs 0%, HR 41·1, 95% CI 9·1-186·6).INTERPRETATION: Both recent immunosuppression and prolonged HIV viraemia have important independent roles in the development of non-Hodgkin lymphoma, with likely subtype heterogeneity. Early and sustained antiretroviral therapy to decrease HIV replication, dampen B-cell activation, and restore overall immune function is crucial for preventing non-Hodgkin lymphoma.FUNDING: National Institutes of Health, Centers for Disease Control and Prevention, US Agency for Healthcare Research and Quality, US Health Resources and Services Administration, Canadian Institutes of Health Research, Ontario Ministry of Health and Long Term Care, and the Government of Alberta.

  View details for PubMedID 30826282

• Association of Viral Suppression With Lower AIDS-Defining and Non-AIDS-Defining Cancer Incidence in HIV-Infected Veterans: A Prospective Cohort Study. Annals of internal medicine Park, L. S., Tate, J. P., Sigel, K., Brown, S. T., Crothers, K., Gibert, C., Goetz, M. B., Rimland, D., Rodriguez-Barradas, M. C., Bedimo, R. J., Justice, A. C., Dubrow, R. 2018

  Abstract

  Background: Viral suppression is a primary marker of HIV treatment success. Persons with HIV are at increased risk for AIDS-defining cancer (ADC) and several types of non-AIDS-defining cancer (NADC), some of which are caused by oncogenic viruses.Objective: To determine whether viral suppression is associated with decreased cancer risk.Design: Prospective cohort.Setting: Department of Veterans Affairs.Participants: HIV-positive veterans (n= 42441) and demographically matched uninfected veterans (n= 104712) from 1999 to 2015.Measurements: Standardized cancer incidence rates and Poisson regression rate ratios (RRs; HIV-positive vs. uninfected persons) by viral suppression status (unsuppressed: person-time with HIV RNA levels ?500 copies/mL; early suppression: initial 2 years with HIV RNA levels <500 copies/mL; long-term suppression: person-time after early suppression with HIV RNA levels <500 copies/mL).Results: Cancer incidence for HIV-positive versus uninfected persons was highest for unsuppressed persons (RR, 2.35 [95% CI, 2.19 to 2.51]), lower among persons with early suppression (RR, 1.99 [CI, 1.87 to 2.12]), and lowest among persons with long-term suppression (RR, 1.52 [CI, 1.44 to 1.61]). This trend was strongest for ADC (unsuppressed: RR, 22.73 [CI, 19.01 to 27.19]; early suppression: RR, 9.48 [CI, 7.78 to 11.55]; long-term suppression: RR, 2.22 [CI, 1.69 to 2.93]), much weaker for NADC caused by viruses (unsuppressed: RR, 3.82 [CI, 3.24 to 4.49]; early suppression: RR, 3.42 [CI, 2.95 to 3.97]; long-term suppression: RR, 3.17 [CI, 2.78 to 3.62]), and absent for NADC not caused by viruses.Limitation: Lower viral suppression thresholds, duration of long-term suppression, and effects of CD4+ and CD8+ T-cell counts were not thoroughly evaluated.Conclusion: Antiretroviral therapy resulting in long-term viral suppression may contribute to cancer prevention, to a greater degree for ADC than for NADC. Patients with long-term viral suppression still had excess cancer risk.Primary Funding Source: National Cancer Institute and National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health.

  View details for PubMedID 29893768

• HIV and Age Do Not Synergistically Affect Age-Related T-Cell Markers. Journal of acquired immune deficiency syndromes (1999) Farhadian, S., Jalbert, E., Deng, Y., Goetz, M. B., Park, L. S., Justice, A. C., Dubrow, R., Emu, B. 2018; 77 (3): 337?44

  Abstract

  Despite major progress in controlling HIV disease through antiretroviral therapy, changes in immune phenotype and function persist in individuals with chronic HIV, raising questions about accelerated aging of the immune system.We conducted a cross-sectional study (2005-2007) of HIV-infected (n = 111) and uninfected (n = 114) men from the Veterans Aging Cohort Study. All HIV-infected subjects were on antiretroviral therapy with VL <400 copies/mL for at least 3 years. T-cell markers were examined using flow cytometry. We evaluated the impact of HIV serostatus and age on T-cell phenotypes (expressed as percentages of the total CD4 and CD8 T-cell population) using multivariate linear regression, adjusted for smoking, alcohol, and race/ethnicity. We tested for interactions between HIV and age by including interaction terms.Among both HIV-infected and uninfected subjects, increasing age was associated with a decreased proportion of naive CD4 T cells (P = 0.014) and CD8 T cells (P < 0.0001). Both HIV infection and increasing age were associated with higher proportions of effector memory CD4 T cells (P < 0.0001 for HIV; P = 0.04 for age) and CD8 T cells (P = 0.0001 for HIV; P = 0.0004 for age). HIV infection, but not age, was associated with a higher proportion of activated CD8 T cells (P < 0.0001). For all T-cell subsets tested, there were no significant interactions between HIV infection and age.Age and HIV status independently altered the immune system, but we found no conclusive evidence that HIV infection and advancing age synergistically result in accelerated changes in age-associated T-cell markers among virally suppressed individuals.

  View details for PubMedID 29140874

  View details for PubMedCentralID PMC5807137

• Impact of HIV and Chronic HCV Status on Advanced HCC Stage in Veterans Torgersen, J., Carbonari, D. M., Kallan, M., Mitchell-Richards, K., Zhang, X., D'Addeo, K., Mehta, R., Park, L. S., Kidwai-Khan, F., Taddei, T., Justice, A. C., Re, V. WILEY. 2017: 764A

  View details for Web of Science ID 000412089801567

• Cancer-Attributable Mortality Among People With Treated Human Immunodeficiency Virus Infection in North America CLINICAL INFECTIOUS DISEASES Engels, E. A., Yanik, E. L., Wheeler, W., Gill, M., Shiels, M. S., Dubrow, R., Althoff, K. N., Silverberg, M. J., Brooks, J. T., Kitahata, M. M., Goedert, J. J., Grover, S., Mayor, A. M., Moore, R. D., Park, L. S., Rachlis, A., Sigel, K., Sterling, T. R., Thorne, J. E., Pfeiffer, R. M., North Amer AIDS Cohort 2017; 65 (4): 636?43

  View details for DOI 10.1093/cid/cix392

  View details for Web of Science ID 000406670800016

• AGE AND HIV DO NOT SYNERGISTICALLY IMPACT T CELL SUBSETS Farhadian, S., Jalbert, E., Deng, Y., Goetz, M., Park, L., Justice, A., Dubrow, R., Emu, B. WILEY. 2017: S122

  View details for Web of Science ID 000402876300348

• Immunological and infectious risk factors for lung cancer in US veterans with HIV: a longitudinal cohort study LANCET HIV Sigel, K., Wisnivesky, J., Crothers, K., Gordon, K., Brown, S. T., Rimland, D., Rodriguez-Barradas, M. C., Gibert, C., Goetz, M. B., Bedimo, R., Park, L. S., Dubrow, R. 2017; 4 (2): E67-E73

  Abstract

  HIV infection is independently associated with risk of lung cancer, but few data exist for the relation between longitudinal measurements of immune function and lung-cancer risk in people living with HIV.We followed up participants with HIV from the Veterans Aging Cohort Study for a minimum of 3 years between Jan 1, 1998, and Dec 31, 2012, and used cancer registry data to identify incident cases of lung cancer. The index date for each patient was the later of the date HIV care began or Jan 1, 1998. We excluded patients with less than 3 years' follow-up, prevalent diagnoses of lung cancer, or incomplete laboratory data. We used Cox regression models to investigate the relation between different time-updated lagged and cumulative exposures (CD4 cell count, CD8 cell count, CD4/CD8 ratio, HIV RNA, and bacterial pneumonia) and risk of lung cancer. Models were adjusted for age, race or ethnicity, smoking, hepatitis C virus infection, alcohol use disorders, drug use disorders, and history of chronic obstructive pulmonary disease and occupational lung disease.We identified 277 cases of incident lung cancer in 21?666 participants with HIV. In separate models for each time-updated 12 month lagged, 24 month simple moving average cumulative exposure, increased risk of lung cancer was associated with low CD4 cell count (p trend=0·001), low CD4/CD8 ratio (p trend=0·0001), high HIV RNA concentration (p=0·004), and more cumulative bacterial pneumonia episodes (12 month lag only; p trend=0·0004). In a mutually adjusted model including these factors, CD4/CD8 ratio and cumulative bacterial pneumonia episodes remained significant (p trends 0·003 and 0·004, respectively).In our large HIV cohort in the antiretroviral therapy era, we found evidence that dysfunctional immune activation and chronic inflammation contribute to the development of lung cancer in the setting of HIV infection. These findings could be used to target lung-cancer prevention measures to high-risk groups.US National Institutes of Health.

  View details for DOI 10.1016/S2352-3018(16)30215-6

  View details for Web of Science ID 000397266500008

  View details for PubMedID 27916584

  View details for PubMedCentralID PMC5444465

• Does radiotherapy still have a role in unresected biliary tract cancer? Cancer medicine Pollom, E. L., Alagappan, M., Park, L. S., Whittemore, A. S., Koong, A. C., Chang, D. T. 2017; 6 (1): 129-141

  Abstract

  The benefits of radiotherapy for inoperable biliary tract cancer remain unclear due to the lack of randomized data. We evaluated the impact of radiotherapy on survival in elderly patients using the SEER-Medicare database. Patients in the SEER-Medicare database with inoperable biliary tract tumors diagnosed between 1998 and 2011 were included. We used multivariate logistic regression to evaluate factors associated with treatment selection, and multivariate Cox regression and propensity score matching to evaluate treatment selection in relation to subsequent survival. Of the 2343 patients included, 451 (19%) received radiotherapy within 4 months of diagnosis. The use of radiotherapy declined over time, and was influenced by receipt of chemotherapy and patient age, race, marital status, poverty status, and tumor stage and type. Median survival was 9.3 (95% CI 8.7-9.7) months among patients who did not receive radiation and 10.0 (95% CI 9.1-11.3) months among those who received radiation, conditional on having survived 4 months. In patients who received chemotherapy (n = 1053), receipt of radiation was associated with improved survival, with an adjusted hazard ratio of 0.82 (95% 0.70-0.97, P = 0.02). In patients who did not receive chemotherapy (n = 1290), receipt of radiation was not associated with improved survival, with an adjusted hazard ratio of 1.09 (95% 0.91-1.30, P = 0.34). Propensity-scored matched analyses showed similar results. Despite the survival benefit associated with the addition of radiotherapy to chemotherapy, the use of radiation for unresectable biliary tract cancers has declined over time.

  View details for DOI 10.1002/cam4.975

  View details for PubMedID 27891822

• Prevalence of non-HIV cancer risk factors in persons living with HIV/AIDS: a meta-analysis AIDS Park, L. S., Hernandez-Ramirez, R. U., Silverberg, M. J., Crothers, K., Dubrow, R. 2016; 30 (2): 273-291

  Abstract

  The burden of cancer among persons living with HIV/AIDS (PLWHA) is substantial and increasing. We assessed the prevalence of modifiable cancer risk factors among adult PLWHA in Western high-income countries since 2000.Meta-analysis.We searched PubMed to identify articles published in 2011-2013 reporting prevalence of smoking, alcohol consumption, overweight/obesity, and infection with human papillomavirus (HPV), hepatitis C virus (HCV) and hepatitis B virus (HBV) among PLWHA. We conducted random effects meta-analyses of prevalence for each risk factor, including estimation of overall, sex-specific, and HIV-transmission-group-specific prevalence. We compared prevalence in PLWHA with published prevalence estimates in US adults.The meta-analysis included 113 publications. Overall summary prevalence estimates were current smoking, 54% [95% confidence interval (CI) 49-59%] versus 20-23% in US adults; cervical high-risk HPV infection, 46% (95% CI 34-58%) versus 29% in US females; oral high-risk HPV infection, 16% (95% CI 10-23%) versus 4% in US adults; anal high-risk HPV infection (men who have sex with men), 68% (95% CI 57-79%), with no comparison estimate available; chronic HCV infection, 26% (95% CI 21-30%) versus 0.9% in US adults; and HBV infection, 5% (95% CI 4-5%) versus 0.3% in US adults. Overweight/obesity prevalence (53%; 95% CI 46-59%) was below that of US adults (68%). Meta-analysis of alcohol consumption prevalence was impeded by varying assessment methods. Overall, we observed considerable study heterogeneity in prevalence estimates.Prevalence of smoking and oncogenic virus infections continues to be extraordinarily high among PLWHA, indicating a vital need for risk factor reduction efforts.

  View details for DOI 10.1097/QAD.0000000000000922

  View details for Web of Science ID 000368013400001

  View details for PubMedID 26691548

  View details for PubMedCentralID PMC4689318

• Time trends in cancer incidence in persons living with HIV/AIDS in the antiretroviral therapy era: 1997-2012. AIDS (London, England) Park, L. S., Tate, J. P., Sigel, K., Rimland, D., Crothers, K., Gibert, C., Rodriguez-Barradas, M. C., Goetz, M. B., Bedimo, R. J., Brown, S. T., Justice, A. C., Dubrow, R. 2016

  Abstract

  Utilizing the Veterans Aging Cohort Study, the largest HIV cohort in North America, we conducted one of the few comprehensive comparisons of cancer incidence time trends in HIV-infected (HIV+) versus uninfected persons during the antiretroviral therapy (ART) era.Prospective cohort study.We followed 44,787 HIV+ and 96,852 demographically-matched uninfected persons during 1997-2012. We calculated age-, sex-, and race/ethnicity-standardized incidence rates (IR) and incidence rate ratios (IRR, HIV+ versus uninfected) over four calendar periods with IR and IRR period trend p-values for cancer groupings and specific cancer types.We observed 3,714 incident cancer diagnoses in HIV+ and 5,760 in uninfected persons. The HIV+ all cancer crude IR increased between 1997-2000 and 2009-2012 (p-trend?=?0.0019). However, after standardization, we observed highly significant HIV+ IR declines for all cancer (25% decline; p-trend<0.0001), AIDS-defining cancers (ADC; 55% decline; p-trend<0.0001), non-AIDS-defining cancers (NADC; 15% decline; p-trend?=?0.0003), and non-virus-related NADC (20% decline; p-trend<0.0001); significant IRR declines for all cancer (from 2.0 to 1.6; p-trend<0.0001), ADC (from 19 to 5.5; p-trend<0.0001), and non-virus-related NADC (from 1.4 to 1.2; p-trend?=?0.049); and borderline significant IRR declines for NADC (from 1.6 to 1.4; p-trend?=?0.078) and virus-related NADC (from 4.9 to 3.5; p-trend?=?0.071).Improved HIV care resulting in improved immune function most likely contributed to the HIV+ IR and the IRR declines. Further promotion of early and sustained ART, improved ART regimens, reduction of traditional cancer risk factor (e.g., smoking) prevalence, and evidence-based screening could contribute to future cancer incidence declines among HIV+ persons.

  View details for PubMedID 27064994

• Comparison of risk and age at diagnosis of myocardial infarction, end-stage renal disease, and non-AIDS-defining cancer in HIV-infected versus uninfected adults. Clinical infectious diseases Althoff, K. N., McGinnis, K. A., Wyatt, C. M., Freiberg, M. S., Gilbert, C., Oursler, K. K., Rimland, D., Rodriguez-Barradas, M. C., Dubrow, R., Park, L. S., Skanderson, M., Shiels, M. S., Gange, S. J., Gebo, K. A., Justice, A. C. 2015; 60 (4): 627-638

  Abstract

  Although it has been shown that human immunodeficiency virus (HIV)-infected adults are at greater risk for aging-associated events, it remains unclear as to whether these events happen at similar, or younger ages, in HIV-infected compared with uninfected adults. The objective of this study was to compare the median age at, and risk of, incident diagnosis of 3 age-associated diseases in HIV-infected and demographically similar uninfected adults.The study was nested in the clinical prospective Veterans Aging Cohort Study of HIV-infected and demographically matched uninfected veterans, from 1 April 2003 to 31 December 2010. The outcomes were validated diagnoses of myocardial infarction (MI), end-stage renal disease (ESRD), and non-AIDS-defining cancer (NADC). Differences in mean age at, and risk of, diagnosis by HIV status were estimated using multivariate linear regression models and Cox proportional hazards models, respectively.A total of 98 687 (31% HIV-infected and 69% uninfected) adults contributed >450 000 person-years and 689 MI, 1135 ESRD, and 4179 NADC incident diagnoses. Mean age at MI (adjusted mean difference, -0.11; 95% confidence interval [CI], -.59 to .37 years) and NADC (adjusted mean difference, -0.10 [95% CI, -.30 to .10] years) did not differ by HIV status. HIV-infected adults were diagnosed with ESRD at an average age of 5.5 months younger than uninfected adults (adjusted mean difference, -0.46 [95% CI, -.86 to -.07] years). HIV-infected adults had a greater risk of all 3 outcomes compared with uninfected adults after accounting for important confounders.HIV-infected adults had a higher risk of these age-associated events, but they occurred at similar ages than those without HIV.

  View details for DOI 10.1093/cid/ciu869

  View details for PubMedID 25362204

• Predicting Risk of End-Stage Liver Disease in Antiretroviral-Treated Human Immunodeficiency Virus/Hepatitis C Virus-Coinfected Patients. Open forum infectious diseases Lo Re, V., Kallan, M. J., Tate, J. P., Lim, J. K., Goetz, M. B., Klein, M. B., Rimland, D., Rodriguez-Barradas, M. C., Butt, A. A., Gibert, C. L., Brown, S. T., Park, L. S., Dubrow, R., Reddy, K. R., Kostman, J. R., Justice, A. C., Localio, A. R. 2015; 2 (3): ofv109

  Abstract

  Background. ?End-stage liver disease (ESLD) is an important cause of morbidity among human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients. Quantifying the risk of this outcome over time could help determine which coinfected patients should be targeted for risk factor modification and HCV treatment. We evaluated demographic, clinical, and laboratory variables to predict risk of ESLD in HIV/HCV-coinfected patients receiving antiretroviral therapy (ART). Methods. ?We conducted a retrospective cohort study among 6016 HIV/HCV-coinfected patients who received ART within the Veterans Health Administration between 1997 and 2010. The main outcome was incident ESLD, defined by hepatic decompensation, hepatocellular carcinoma, or liver-related death. Cox regression was used to develop prognostic models based on baseline demographic, clinical, and laboratory variables, including FIB-4 and aspartate aminotransferase-to-platelet ratio index, previously validated markers of hepatic fibrosis. Model performance was assessed by discrimination and decision curve analysis. Results. ?Among 6016 HIV/HCV patients, 532 (8.8%) developed ESLD over a median of 6.6 years. A model comprising FIB-4 and race had modest discrimination for ESLD (c-statistic, 0.73) and higher net benefit than alternative strategies of treating no or all coinfected patients at relevant risk thresholds. For FIB-4 >3.25, ESLD risk ranged from 7.9% at 1 year to 26.0% at 5 years among non-blacks and from 2.4% at 1 year to 14.0% at 5 years among blacks. Conclusions. ?Race and FIB-4 provided important predictive information on ESLD risk among HIV/HCV patients. Estimating risk of ESLD using these variables could help direct HCV treatment decisions among HIV/HCV-coinfected patients.

  View details for PubMedID 26284259

• Hepatic decompensation in antiretroviral-treated patients co-infected with HIV and hepatitis C virus compared with hepatitis C virus-monoinfected patients: a cohort study. Annals of internal medicine Lo Re, V., Kallan, M. J., Tate, J. P., Localio, A. R., Lim, J. K., Goetz, M. B., Klein, M. B., Rimland, D., Rodriguez-Barradas, M. C., Butt, A. A., Gibert, C. L., Brown, S. T., Park, L., Dubrow, R., Reddy, K. R., Kostman, J. R., Strom, B. L., Justice, A. C. 2014; 160 (6): 369-379

  Abstract

  The incidence and determinants of hepatic decompensation have been incompletely examined among patients co-infected with HIV and hepatitis C virus (HCV) in the antiretroviral therapy (ART) era, and few studies have compared outcome rates with those of patients with chronic HCV alone.To compare the incidence of hepatic decompensation between antiretroviral-treated patients co-infected with HIV and HCV and HCV-monoinfected patients and to evaluate factors associated with decompensation among co-infected patients receiving ART.Retrospective cohort study.Veterans Health Administration.4280 co-infected patients who initiated ART and 6079 HCV-monoinfected patients receiving care between 1997 and 2010. All patients had detectable HCV RNA and were HCV treatment-naive.Incident hepatic decompensation, determined by diagnoses of ascites, spontaneous bacterial peritonitis, or esophageal variceal hemorrhage.The incidence of hepatic decompensation was greater among co-infected than monoinfected patients (7.4% vs. 4.8% at 10 years; P < 0.001). Compared with HCV-monoinfected patients, co-infected patients had a higher rate of hepatic decompensation (hazard ratio [HR] accounting for competing risks, 1.56 [95% CI, 1.31 to 1.86]). Co-infected patients who maintained HIV RNA levels less than 1000 copies/mL still had higher rates of decompensation than HCV-monoinfected patients (HR, 1.44 [CI, 1.05 to 1.99]). Baseline advanced hepatic fibrosis (FIB-4 score >3.25) (HR, 5.45 [CI, 3.79 to 7.84]), baseline hemoglobin level less than 100 g/L (HR, 2.24 [CI, 1.20 to 4.20]), diabetes mellitus (HR, 1.88 [CI, 1.38 to 2.56]), and nonblack race (HR, 2.12 [CI, 1.65 to 2.72]) were each associated with higher rates of decompensation among co-infected patients.Observational study of predominantly male patients.Despite receiving ART, patients co-infected with HIV and HCV had higher rates of hepatic decompensation than HCV-monoinfected patients. Rates of decompensation were higher for co-infected patients with advanced liver fibrosis, severe anemia, diabetes, and nonblack race.National Institutes of Health.

  View details for DOI 10.7326/M13-1829

  View details for PubMedID 24723077

• Cancer Incidence in HIV-Infected Versus Uninfected Veterans: Comparison of Cancer Registry and ICD-9 Code Diagnoses. Journal of AIDS & clinical research Park, L. S., Tate, J. P., Rodriguez-Barradas, M. C., Rimland, D., Goetz, M. B., Gibert, C., Brown, S. T., Kelley, M. J., Justice, A. C., Dubrow, R. 2014; 5 (7): 1000318

  Abstract

  Given the growing interest in the cancer burden in persons living with HIV/AIDS, we examined the validity of data sources for cancer diagnoses (cancer registry versus International Classification of Diseases, Ninth Revision [ICD-9 codes]) and compared the association between HIV status and cancer risk using each data source in the Veterans Aging Cohort Study (VACS), a prospective cohort of HIV-infected and uninfected veterans from 1996 to 2008.We reviewed charts to confirm potential incident cancers at four VACS sites. In the entire cohort, we calculated cancer-type-specific age-, sex-, race/ethnicity-, and calendar-period-standardized incidence rates and incidence rate ratios (IRR) (HIV-infected versus uninfected). We calculated standardized incidence ratios (SIR) to compare VACS and Surveillance, Epidemiology, and End Results rates.Compared to chart review, both Veterans Affairs Central Cancer Registry (VACCR) and ICD-9 diagnoses had approximately 90% sensitivity; however, VACCR had higher positive predictive value (96% versus 63%). There were 6,010 VACCR and 13,386 ICD-9 incident cancers among 116,072 veterans. Although ICD-9 rates tended to be double VACCR rates, most IRRs were in the same direction and of similar magnitude, regardless of data source. Using either source, all cancers combined, most viral-infection-related cancers, lung cancer, melanoma, and leukemia had significantly elevated IRRs. Using ICD-9, eight additional IRRs were significantly elevated, most likely due to false positive diagnoses. Most ICD-9 SIRs were significantly elevated and all were higher than the corresponding VACCR SIR.ICD-9 may be used with caution for estimating IRRs, but should be avoided when estimating incidence or SIRs. Elevated cancer risk based on VACCR diagnoses among HIV-infected veterans was consistent with other studies.

  View details for DOI 10.4172/2155-6113.1000318

  View details for PubMedID 25580366

  View details for PubMedCentralID PMC4285627

• Time trends in glioblastoma multiforme survival: the role of temozolomide NEURO-ONCOLOGY Dubrow, R., Darefsky, A. S., Jacobs, D. I., Park, L. S., Rose, M. G., Laurans, M. S., King, J. T. 2013; 15 (12): 1750-1761

  Abstract

  In 2005, maximum safe surgical resection, followed by radiotherapy with concomitant temozolomide (TMZ), followed by adjuvant TMZ became the standard of care for glioblastoma (GBM). Furthermore, a modest, but meaningful, population-based survival improvement for GBM patients occurred in the US between 1999 (when TMZ was first introduced) and 2008. We hypothesized that TMZ usage explained this GBM survival improvement.We used national Veterans Health Administration (VHA) databases to construct a cohort of GBM patients, with detailed treatment information, diagnosed 1997-2008 (n = 1645). We compared survival across 3 periods of diagnosis (1997-2000, 2001-2004, and 2005-2008) using Kaplan-Meier curves. We used proportional hazards models to calculate period hazard rate ratios (HRs) and 95% confidence intervals (CIs), adjusted for demographic, clinical, and treatment covariates.Survival increased over calendar time (stratified log-rank P < .0001). After adjusting for age and Charlson comorbidity score, for cases diagnosed in 2005-2008 versus 1997-2000, the HR was 0.72 (95% CI, 0.64-0.82; p-trend < .0001). Sequentially adding non-TMZ treatment variables (ie, surgery, radiotherapy, non-TMZ chemotherapy) to the model did not change this result. However, adding TMZ to the model containing age, Charlson comorbidity score, and all non-TMZ treatments eliminated the period effect entirely (HR = 1.01; 95% CI, 0.86-1.19; p-trend = 0.84).The observed survival improvement among GBM patients diagnosed in the VHA system between 1997 and 2008 was completely explained by TMZ. Similar studies in other populations are warranted to test the generalizability of our finding to other patient cohorts and health care settings.

  View details for DOI 10.1093/neuonc/not122

  View details for Web of Science ID 000327455600017

  View details for PubMedID 24046259

• HIV infection, aging, and immune function: implications for cancer risk and prevention CURRENT OPINION IN ONCOLOGY Dubrow, R., Silverberg, M. J., Park, L. S., Crothers, K., Justice, A. C. 2012; 24 (5): 506-516

  Abstract

  Combination antiretroviral therapy (ART) has turned HIV infection into a complex chronic disease. This article documents cancer risk among HIV-infected persons, reviews immune system effects of HIV infection in relation to cancer risk, discusses implications for cancer prevention, and suggests future research directions.There has been a shift in the cancer spectrum from AIDS-defining cancers (ADC) to non-ADC, although the burden of ADC remains high. Although a high prevalence of non-HIV cancer risk factors among HIV-infected persons contributes to cancer risk, substantial evidence has accumulated in favor of an independent association between HIV-induced immunodeficiency and elevated risk of many specific cancer types, most of viral cause, although further work is needed to disentangle immunodeficiency and smoking effects for lung cancer, and immunodeficiency and hepatitis virus effects for liver cancer. Relationships between cancer risk and two other immune system hallmarks of HIV infection, chronic inflammation, and immune dysfunction/senescence, remain poorly understood.Early, sustained ART is a crucial component of cancer prevention. Continued epidemiologic monitoring is needed to detect possible effects on cancer risk of specific ART classes or medications, long-term exposure to systemic inflammation or immune dysfunction, or earlier or more effective ART.

  View details for DOI 10.1097/CCO.0b013e328355e131

  View details for Web of Science ID 000307681500007

  View details for PubMedID 22759737

• HIV as an independent risk factor for incident lung cancer AIDS Sigel, K., Wisnivesky, J., Gordon, K., Dubrow, R., Justice, A., Brown, S. T., Goulet, J., Butt, A. A., Crystal, S., Rimland, D., Rodriguez-Barradas, M., Gibert, C., Park, L. S., Crothers, K. 2012; 26 (8): 1017-1025

  Abstract

  It is unclear whether the elevated rate of lung cancer among HIV-infected persons is due to biological effects of HIV, surveillance bias, or excess smoking. We compared the incidence of lung cancer between HIV-infected and demographically similar HIV-uninfected patients, accounting for smoking and stage of lung cancer at diagnosis.Data from the Veterans Aging Cohort Study Virtual Cohort were linked to data from the Veterans Affairs Central Cancer Registry, resulting in an analytic cohort of 37,294 HIV-infected patients and 75,750 uninfected patients.We calculated incidence rates of pathologically confirmed lung cancer by dividing numbers of cases by numbers of person-years at risk. We used Poisson regression to determine incidence rate ratios (IRRs), adjusting for age, sex, race/ethnicity, smoking prevalence, previous bacterial pneumonia, and chronic obstructive pulmonary disease.The incidence rate of lung cancer in HIV-infected patients was 204 cases per 100,000 person-years [95% confidence interval (CI) 167-249] and among uninfected patients was 119 cases per 100,000 person-years (95% CI 110-129). The IRR of lung cancer associated with HIV infection remained significant after multivariable adjustment (IRR 1.7; 95% CI 1.5-1.9). Lung cancer stage at presentation did not differ between HIV-infected and uninfected patients.In our cohort of demographically similar HIV-infected and uninfected patients, HIV infection was an independent risk factor for lung cancer after controlling for potential confounders including smoking. The similar stage distribution between the two groups indicated that surveillance bias was an unlikely explanation for this finding.

  View details for DOI 10.1097/QAD.0b013e328352d1ad

  View details for Web of Science ID 000303656000013

  View details for PubMedID 22382152

• FIB-4 Index Is Associated with Hepatocellular Carcinoma Risk in HIV-Infected Patients CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Park, L. S., Tate, J. P., Justice, A. C., Lo Re, V., Lim, J. K., Braeu, N., Brown, S. T., Butt, A. A., Gibert, C., Goetz, M. B., Rimland, D., Rodriguez-Barradas, M. C., Dubrow, R. 2011; 20 (12): 2512-2517

  Abstract

  Chronic inflammation caused by hepatitis B virus infection, hepatitis C virus infection, and/or heavy alcohol use can lead to fibrosis, cirrhosis, and eventually hepatocellular carcinoma (HCC). FIB-4 is an index score calculated from platelet count, alanine transaminase, aspartate transaminase, and age that predicts fibrosis and cirrhosis. We hypothesized that high FIB-4 would be associated with development of HCC in HIV-infected persons, who are at high risk due to high prevalence of viral hepatitis and alcohol consumption, and possibly due to HIV infection itself.Using proportional hazards models, we tested this hypothesis among 22,980 HIV-infected men from the Veterans Aging Cohort Study. We identified incident HCC cases from the Veterans Affairs Central Cancer Registry.During follow-up, there were 112 incident HCC diagnoses. The age- and race/ethnic group-adjusted HR was 4.2 [95% confidence interval (CI), 2.4-7.4] for intermediate FIB-4 and 13.0 (95% CI, 7.2-23.4) for high FIB-4, compared with low FIB-4. After further adjustment for enrollment year, CD4 count, HIV-1 RNA level, antiretroviral therapy use, hepatitis B and C virus infection, alcohol abuse/dependency, and diabetes, FIB-4 remained a strong, significant, independent risk factor for HCC. The multivariate-adjusted HR was 3.6 (95% CI, 2.1-6.4) for intermediate FIB-4 and 9.6 (95% CI, 5.2-17.4) for high FIB-4.Calculated from routine, noninvasive laboratory tests, FIB-4 is a strong, independent HCC risk factor in HIV-infected patients.FIB-4 might prove valuable as an easily measured index to identify those at highest risk for HCC, even prior to development of clinical cirrhosis.

  View details for DOI 10.1158/1055-9965.EPI-11-0582

  View details for Web of Science ID 000298234900006

  View details for PubMedID 22028407

• Rehospitalization among Elderly Patients with Thyroid Cancer after Thyroidectomy are Prevalent and Costly ANNALS OF SURGICAL ONCOLOGY Tuggle, C. T., Park, L. S., Roman, S., Udelsman, R., Sosa, J. A. 2010; 17 (11): 2816-2823

  Abstract

  Thyroid cancer increases in incidence and aggressiveness with age. The elderly are the fastest growing segment of the U.S. population. Reducing rates of rehospitalization would lower cost and improve quality of care. This is the first study to report population-level information characterizing rehospitalization after thyroidectomy among the elderly.The Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked database was used to identify patients older than aged 65 years with thyroid cancer who underwent thyroidectomy from 1997-2002. Patient and hospital characteristics were studied to predict the risk of rehospitalization. Outcomes were 30-day unplanned rehospitalization rate, cost, and length of stay (LOS) of readmission.Of 2,127 patients identified, 69% were women, 84% had differentiated thyroid cancer, and 52% underwent total thyroidectomy. Mean age was 74 years. A total of 171 patients (8%) underwent 30-day unplanned rehospitalization. Rehospitalization was associated with increased comorbidity, advanced stage, number of lymph nodes examined, increased LOS of index admission, and small hospital size (all P < 0.05). Patients with a complication during index hospital stay were more likely to be readmitted (P < 0.001), whereas patients who saw an outpatient medical provider after index discharge returned less frequently (P < 0.001). Forty-seven percent of readmissions were for endocrine-related causes. Mean LOS and cost of rehospitalization were 3.5 days and $5,921, respectively. Unplanned rehospitalization was associated with death at 1 year compared with nonrehospitalized patients (18% vs. 6%; P < 0.001).Rehospitalization among Medicare beneficiaries with thyroid cancer after thyroidectomy is prevalent and costly. Further study of predictors could identify high-risk patients for whom enhanced preoperative triage, improved discharge planning, and increased outpatient support might prove cost-effective.

  View details for DOI 10.1245/s10434-010-1144-7

  View details for Web of Science ID 000283400900003

  View details for PubMedID 20552406

• HIV Transmission Rates in Thailand: Evidence of HIV Prevention and Transmission Decline JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES Park, L. S., Siraprapasiri, T., Peerapatanapokin, W., Manne, J., Niccolai, L., Kunanusont, C. 2010; 54 (4): 430-436

  Abstract

  Analysis of HIV transmission rates has provided insight into the impacts of HIV-related prevention programming and policies in the United States by providing timely information beyond incidence or prevalence alone. The purpose of this analysis is to use transmission rates to assess past prevention efforts and explore trends of the epidemic in subpopulations within Thailand.Asian Epidemic Model HIV incidence and prevalence were used to calculate transmission rates over time nationally and among high-risk populations.A national HIV/AIDS program implemented in Thailand in the 1990s that targeted sex workers and the general population was correlated with a decrease in new cases despite high prevalence. The turning point of the epidemic was in 1991 when the national transmission rate was 32%. By the late 1990s, the rate dropped to less than 4%. All subpopulations experienced a rate decline; however, sex workers still experienced higher transmission rates.The declining trend in HIV transmission rates despite ever-growing prevalence indicates prevention success correlated with the national HIV/AIDS program. Data from subgroup analyses provide stronger evidence of prevention success than incidence alone, as this measure demonstrates the effect of efforts and accounts for the burden of disease in the population.

  View details for DOI 10.1097/QAI.0b013e3181dc5dad

  View details for Web of Science ID 000280013600014

  View details for PubMedID 20418773

• Effects of active HCV replication on neurologic status in HIV RNA virally suppressed patients NEUROLOGY Clifford, D. B., Smurzynski, M., Park, L. S., Yeh, T., Zhao, Y., Blair, L., Arens, M., Evans, S. R. 2009; 73 (4): 309-314

  Abstract

  Hepatitis C virus (HCV) is a frequent copathogen with HIV. Both viruses appear to replicate in the brain and both are implicated in neurocognitive and peripheral neuropathy syndromes. Interaction of the viruses is likely to be complicated and better understanding of the contributions of each virus will be necessary to make evidence-based therapeutic decisions.This study was designed to determine if active HCV infection, identified by quantitative HCV RNA determination, is associated with increased neurocognitive deficits or excess development of distal sensory peripheral neuropathy in HIV coinfected patients with stable HIV viral suppression. The AIDS Clinical Trials Group Longitudinal Linked Randomized Trials (ALLRT) study was the source of subjects with known HIV treatment status, neurocognitive and neuropathy evaluations, and HCV status. Subjects were selected based on HCV antibody status (249 positive; 310 negative).HCV RNA viral loads were detectable in 172 participants with controlled HIV infection and available neurologic evaluations in the ALLRT. These participants were compared with 345 participants with undetectable HCV viral load and the same inclusion criteria from the same cohort. Neurocognitive performance measured by Trail-Making A or B and digit symbol testing was not dissimilar between the 2 groups. In addition, there was no significant association between active HCV replication and distal sensory neuropathy.Clinically significant neurocognitive dysfunction and peripheral neuropathy were not exacerbated by active hepatitis C virus infection in the setting of optimally treated HIV infection.

  View details for DOI 10.1212/WNL.0b013e3181af7a10

  View details for Web of Science ID 000268356500010

  View details for PubMedID 19636051