12157 Background: Despite the rapidly increasing trend in incidence of prostate cancer among persons with HIV (PWH), comprehensive data outlining outcomes and treatment toxicities of prostate cancer in this population remain sparse. Notably, both HIV infection and prostate cancer treatment independently increase the risk of cardiovascular disease. We sought to quantify the risk of major cardiovascular adverse events (MACE) among a large Veterans Affairs (VA) cohort of PWH and people without HIV (PWoH). Methods: We used patient data from the VA Corporate Data Warehouse and the VA Central Cancer Registry, including demographics, laboratory data, medications administered in inpatient/outpatient pharmacies, International Classification of Diseases 9 th Edition and 10 th edition diagnoses and procedure codes. Patients were included if they had diagnosis of prostate adenocarcinoma between 1/1/2008 and 12/31/2020. Patients were excluded if they had a diagnosis with any prior invasive cancer on or prior to prostate cancer diagnosis, diagnosis with prostate cancer prior to HIV positive diagnosis, or MACE within 6 months prior to prostate cancer diagnosis. MACE was defined as having a diagnosis code of myocardial infarction, stroke, or arrhythmia, within five years of start of treatment approach for prostate cancer (defined as androgen deprivation therapy (ADT) or active surveillance). We conducted a time-to-event analysis using the Cox proportional hazards model to examine the time to first occurrence of MACE, accounting for censoring and varying follow-up times. Results: A total of 87,144 prostate cancer patients were included (654 PWH and 86,490 PWoH). About 37.5% of PWH were < 60-years-old at time of prostate cancer diagnosis (compared with 19.6% of PWoH). Among 62,259 patients with low-risk or intermediate-risk localized prostate cancer, the risk of MACE was 24% greater among PWH compared with PWoH (HR 1.24, 95% CI 1.02-1.51, p = 0.03) after controlling for age, race, and cardiovascular risk factors at time of cancer diagnosis. Among PWH with prostate cancer, receiving ADT was associated with a 3.5 fold increased risk of developing MACE vs. those not receiving ADT (HR 3.51, 95% CI 2.25-5.49, p < 0.01). Among PWoH with prostate cancer, receiving ADT had a 2.7-fold increased risk of developing MACE vs. those not receiving ADT (HR 2.72, 95% CI 2.61-2.84). Conclusions: Both HIV infection and ADT increase the risk of MACE among prostate cancer patients. Future studies are warranted to explore the mechanistic links between HIV infection, ADT, and cardiovascular health.

8070 Background: Since the widespread introduction of antiretroviral therapy (ART), people living with HIV (PWH) have experienced substantially decreased morbidity and mortality. However, PWH are at higher risk for lung cancer and have decreased cancer survival rates compared to people without HIV (PWoH). Few studies have evaluated histology-specific lung cancer survival by stage and HIV immune control. Methods: A retrospective cohort study was conducted with newly diagnosed non-small cell lung cancer (NSCLC), including PWH with PWoH, identified between 2008 and 2020 from the US Department of Veterans Affairs and Kaiser Permanente, California. Adjusted hazard ratios for 5-year survival by CD4 count (≥ 500 cells/mm3, <500 cells/mm3, ref: PwOH) were estimated using Cox models stratified by subtype (adenocarcinoma, squamous) and TNM (I, II/III, IV) stage. Results: This cohort consisted of 562 PWH (53% adenocarcinoma, 33% squamous cell) and 91,370 PWoH (52% adenocarcinoma, 33% squamous cell, 15% not specified). The PWH cohort tended to be younger (62 vs. 69 years), male (97% vs. 83%), and non-Hispanic Black race (48% vs. 14%), compared to PWoH. Among PWH, 41% had CD4 ≥500 cells/mm3, 59% had CD4 <500 cells/mm3 . The median survival in years for PWoH, PWH CD4 count ≥500 cell/mm3and <500 cells/mm3 were: 2.4 ±0.10, 2.3 ± 0.17, 2.0±0.17, respectively for adenocarcinoma, and 2.1±0.01, 2.3±0.21, 1.6±0.17 respectively for squamous cell carcinoma. The table shows the adjusted HR for all-cause mortality for Adenocarcinoma and Squamous Cell Carcinoma comparing PWH ≥500 and PWH<500 to PWoH (as reference) stratified by stage. Conclusions: Although it is well known that low CD counts (<200) are associated with poor cancer outcomes, higher CD4 counts (CD<500) at the time of lung cancer diagnosis may still play a role in the treatment outcomes of NSCLC. PWH who have CD4 counts ≥500 appear to have similar survival compared to PWoH, but CD4<500, those with (vs. without) HIV have higher rates of mortality for both adenocarcinoma and squamous cell histologies. Adjusted hazard ratios (HR)* with 95% confidence intervals (CI) for 5-year all-cause-mortality associated with HIV by CD4 count (reference: PWoH), across Adenocarcinoma and Squamous Cell Cancer histology and baseline cancer stage. [Table: see text]

Objectives:People with HIV (PWH) may have an increased burden of penile cancer. We aimed to evaluate the risk of penile cancer in PWH compared with that of the general population.Design:We conducted a nationwide retrospective matched cohort study of penile cancer incidence among veterans with HIV (VWH) compared with veterans without HIV.Methods:We compared penile cancer incidence rates in 44 173 VWH to those of veterans without HIV (N = 159 443; 4 : 1 matched in age). We used Cox regression models to estimate hazard ratios and 95% confidence intervals (CIs) for associations with HIV infection and for penile cancer risk factors.Results:HIV positivity was associated with an increased risk of penile cancer, with adjusted hazard ratios of 2.63 (95% CI 1.64-4.23) when adjusting for age, race/ethnicity, baseline BMI, smoking and alcohol use, economic means test, and history of condyloma. The risk increased to hazard ratio = 4.25 (95% CI 2.75-6.57) when adjusting for all factors except history of condyloma. Risk factors for penile cancer in VWH included lower nadir CD4+ count, less than 50% of follow-up time with undetectable HIV viral load, and history of condyloma.Conclusion:VWH - particularly those with low CD4+ counts, detectable HIV viral loads, or history of condyloma - are at increased risk of penile cancer, suggesting the penile cancer prevention activities are needed in this population.

Background Preventing HIV infection remains a critically important tool in the continuing fight against HIV/AIDS. The primary aim is to evaluate the effect and interactions between a composite area-level social determinants of health measure and an area-level measure of residential segregation on the risk of HIV/AIDS in U.S. Veterans.Methods Using the individual-level patient data from the U.S. Department of Veterans Affairs, we constructed a case- control study of veterans living with HIV/AIDS (VLWH) and age-, sex assigned at birth-and index date-matched controls. We geocoded patient's residential address to ascertain their neighborhood and linked their information to two measures of neighborhood-level disadvantage: area deprivation index (ADI) and isolation index (ISOL). We used logistic regression to estimate the odds ratio (OR) and 95% confidence interval (CI) for comparing VLWH with matched controls. We performed analyses for the entire U.S. and separately for each U.S. Census division.Findings Overall, living in minority-segregated neighborhoods was associated with a higher risk of HIV (OR: 1.88 (95% CI: 1.79-1.97) while living in higher ADI neighborhoods was associated with a lower risk of HIV (OR: 0.88; 95% CI: 0.84-0.92). The association between living in a higher ADI neighborhood and HIV was inconsistent across divisions, while living in minority-segregated neighborhoods was consistently associated with increased risk across all divisions. In the interaction model, individuals from low ADI and high ISOL neighborhoods had a higher risk of HIV in three divisions: East South Central; West South Central, and Pacific.Interpretation Our results suggest that residential segregation may prevent people in disadvantaged neighborhoods from protecting themselves from HIV independent from access to health care. There is the need to advance knowledge about the neighborhood-level social-structural factors that influence HIV vulnerability toward developing interventions needed to achieve the goal of ending the HIV epidemic.Funding US National Cancer Institute.Copyright (c) 2023 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Background Persons living with HIV/AIDS have a higher incidence of virus‐related and tobacco/alcohol‐related cancers. This study is the first to estimate the effect of HIV versus HIV‐negative veterans on the risk of head and neck squamous cell carcinoma incidence in a large retrospective cohort study. Methods The authors constructed a retrospective cohort study using patient data from 1999 to 2016 from the National Veterans Administration Corporate Data Warehouse and the VA Central Cancer Registry. This cohort study included 45,052 veterans living with HIV/AIDS and 162,486 HIV‐negative patients matched by age, sex, and index visit (i.e., HIV diagnosis date or clinic visit date). The age‐standardized incidence rates and estimated adjusted hazard ratios were calculated with a Cox proportional hazards regression for oropharyngeal and nonoropharyngeal head and neck cancer squamous cell carcinoma (HNSCC). The authors also abstracted human papillomavirus (HPV) status from oropharyngeal HNSCC diagnosed after 2010. Results Veterans living with HIV/AIDS (VLWH) have 1.71 (95% confidence interval [CI], 1.36, 2.14) times the risk of oropharyngeal cancer and 2.06 (95% CI, 1.76, 2.42) times the hazard of nonoropharyngeal cancer compared with HIV‐negative veterans. VLWH with oropharyngeal squamous cell carcinoma (OPSCC) were more likely to be HPV‐positive ( N = 30 [81.1%]) than the HIV‐negative veterans with OPSCC ( N = 50 [67.6%]), although this difference was not significant ( p = .135). For nonoropharyngeal cancer, the increased risk of oral cavity cancer among VLWH drove the increased risk. Conclusions The study results suggest that HIV may play a role in virally mediated and nonvirally mediated HNSCC. As the HIV prevalence rises in the United States due to better survival and the incidence of HPV‐positive oropharyngeal HNSCC increases, the interaction between HPV and HIV becomes increasingly relevant.

OBJECTIVE:People living with HIV have high rates of obesity and obesity-related comorbidities. Our study sought to evaluate weight trajectory in a retrospective cohort of people living with HIV and matched HIV-negative veterans (controls) and to evaluate risk factors for weight gain.METHODS:This was a retrospective database analysis of data extracted from the VA Corporate Data Warehouse that included people living with HIV (n = 22 421) and age-matched HIV-negative controls (n = 63 072). The main outcomes were baseline body weight and weight change from baseline at 1, 2, and 5 years after diagnosis (baseline visit for controls).RESULTS:Body weight at baseline was lower in people living with HIV than in controls. People living with HIV on antiretroviral therapy (ART) gained more weight than did controls. In a sub-analysis of ART-exposed people living with HIV, age >50 years, African American race, body mass index (BMI) <25, CD4 ≤200, and HIV diagnosis year after 2000 were associated with more weight gain at year 1. Nucleoside reverse transcriptase inhibitors (NRTI) plus non-NRTIs (NNRTIs) were associated with less weight gain than NRTIs plus protease inhibitors, NRTIs plus integrase inhibitors, or NRTIs plus other agents at year 1.CONCLUSIONS:Among US veterans, those living with HIV had lower rates of obesity than age-matched HIV-negative controls; however, primarily in the first 2 years after starting ART, people living with HIV gained more weight than did controls.

Background: Preventing HIV infection remains a critically important tool in the continuing fight against HIV/AIDS. The primary aim of this analysis is to evaluate the effect and interactions between a composite area-level social determinants of health measure and an area-level measure of residential segregation on the risk of HIV/AIDS in U.S. Veterans.Methods: Using the individual-level patient data from the U.S. Department of Veterans Affairs, we constructed a case-control study of veterans living with HIV/AIDS (VLWH) and age-, gender- and index date-matched controls. We geocoded patient’s residential address to ascertain their neighborhood and linked their information to two measures of neighborhood-level disadvantage: area deprivation index (ADI) and isolation index (ISOL). We used logistic regression to estimate the odds ratio (OR) and 95% confidence interval (CI) for comparing VLWH with matched controls. We performed analyses for the entire U.S. and separately for each U.S. Census division.Findings: Overall, living in minority-segregated neighborhoods was associated with a higher risk of HIV (OR: 1.88 (95% CI: 1.79-1.97) while living in higher ADI neighborhoods was associated with a lower risk of HIV (OR: 0.88; 95% CI: 0.84-0.92). The association between living in a higher ADI neighborhood and HIV was inconsistent across divisions, while living in minority-segregated neighborhoods was consistently associated with increased risk across all divisions. In the interaction model, individuals from low ADI and high ISOL neighborhoods had a higher risk of HIV in three divisions: East South Central; West South Central, and Pacific.Interpretation: Our results suggest that residential segregation may prevent people in disadvantaged neighborhoods from protecting themselves from HIV independent from access to health care. There is the need to advance knowledge about the neighborhood-level social-structural factors that influence HIV vulnerability toward developing interventions needed to achieve the goal of ending the HIV epidemic.Funding: This study was funded and supported by grant R01CA206476 (Drs Chiao and Kramer; P.I.s) from the National Cancer Institute. Grant CIN13-413 from the Houston Veterans Affairs Health Services Research and Development Center of Innovations. Grant P30 CA125123 from the Baylor College of Medicine Dan L. Duncan Cancer Center. Grant K01MD013897 (Dr. Mazul) from the National Institute of Minority Health and Health Disparities. Dr. Oluyomi’s effort was supported in part by grant P30ES030285 (Dr. Walker; P.I.) from the National Institute of Environmental Health. Declaration of Interest: Conflict of Interest Disclosures: None reported.Ethical Approval: The Institutional Review Board of Baylor College of Medicine and the Michael E. DeBakey VA Medical Center approved this study.

Oropharyngeal squamous cell carcinoma (OPSCC) epidemiology has not been examined previously in the nationwide Veterans Affairs (VA) population.

Background People living with HIV/AIDS (PLWH) have an excess risk for head and neck squamous cell carcinoma (HNSCC) compared to the general U.S. population, but little is known about HIV-specific risk factors associated with the incidence and outcomes HNSCC. We aim to identify clinical and HIV-specific risk factors associated with oropharyngeal and non-oropharyngeal HNSCC incidence and outcomes separately. Methods We constructed a retrospective cohort study of 45,052 PLWH aged 18 or above from the national Veteran Affairs (VA) Corporate Data from 1999 to 2015. We extracted demographic data and risk factor information, including history of alcohol abuse, smoking, CD4 count (cells/mu l), and percent of follow-up time with undetectable HIV viral load as time-updated variables. We calculated the age-standardized incidence rates of oropharyngeal and non-oropharyngeal HNSCC and estimated adjusted hazard ratios (HR). We also examined overall survival using Kaplan-Meier curves and adjusted HR. Results The standardized incidence rate of oropharyngeal and non-oropharyngeal HNSCC in this veteran cohort of PLWH is 23.0 (95% confidence intervals (CIs): 17.1-28.9) and 55.4 (95% CI: 46.5-64.3) per 100,000 person-years, respectively. Nadir CD4 count <= 200 was associated with an increased risk of non-oropharyngeal HNSCC (HR: 1.78; 95% CI: 1.31-2.30 vs >200). Five-year overall survival of OPSCC (37.0%) was significantly lower than non-oropharyngeal HNSCC (49.1%). Conclusions PLWH who receive care in the VA had higher age-adjusted HNSCC incidence rates than reported in the general population, suggesting that HIV and immunosuppression play a role. Additional studies should be conducted to study the interaction between HPV and HIV.

Among people living with HIV (PWH), there has been an increasing incidence of non-small cell lung cancer (NSCLC) and metabolic abnormalities, including dyslipidemia, which can modulate NSCLC risk. In this article, we evaluate which metabolic risk factors are associated with incident risk among PWH who smoke. This is done through a retrospective cohort study, using data of HIV+ veterans who smoke from the nationwide Veterans Affairs (VA) healthcare system. Data on diagnostic codes, medication, and laboratory values of 33,351 veterans were obtained using the VA’s Corporate Data Warehouse and Central Cancer Registry. We calculated NSCLC incidence and utilized Cox regression to determine metabolic factors associated with NSCLC risk. HIV+ cohort was 97.4% male; median age = 47 years and 20,050 (60.1%) well-controlled (≥80% follow-up time undetectable viral load). Crude incidence rates were lower in well-controlled PWH (1.46 vs. 2.06/1000 PY). Metabolic factors associated with incident NSCLC risk included lower BMI at HIV diagnosis and cachexia history in both groups, while HDL and triglycerides were significant in non-well-controlled smokers only. Our findings that lower BMI at HIV diagnosis, history of cachexia among individuals with well-controlled HIV, and cachexia presence at diagnosis are associated with increased risk of developing NSCLC in PWH with a history of smoking have important implications.

(a) Although prostate cancer is projected to be one of the most frequently diagnosed cancers in HIV-infected men overall, little is known about its risk in the sub-group with well-controlled HIV-infection. (b) We performed a retrospective cohort study to determine age-adjusted incidence of prostate adenocarcinoma in HIV-positive male veterans utilizing Veterans Administration (VA) healthcare between 10/01/1999 and 12/31/2016. HIV infection and prostate adenocarcinoma diagnosis as well as related clinical, sociodemographic, and lifestyle risk factors were obtained using extant VA administrative healthcare databases, the VA cancer registry, and augmented prostate cancer diagnosis with direct electronic medical record (EMR) review. We defined well controlled HIV as >60% of time with an undetectable HIV viral load and limited our analyses to those with a minimum of 90 days between HIV and prostate diagnosis, death, their last recorded health care encounter, or study end. We employed time-varying Cox proportional hazard regression models and used backward elimination to identify risk factors associated with incident prostate adenocarcinoma; effects are reported as Hazard ratios (HR) and 95% confidence intervals (CI). (c) During an average 10.26 years of follow-up, we identified 587 incident prostate adenocarcinomas among our cohort of 19,079 HIV positive men with well-controlled infection (age-adjusted incidence rate [IR] = 83.31 per 100,000-person years, 95% CI: 76.83-90.33); with a significant increasing trend over time. We identified several factors associated with significant increased risk of incident prostate adenocarcinoma, after adjusting for HIV medication use, in our well-controlled HIV-positive cohort including substance abuse (HR=1.68, 95% CI: 1.27-2.24, p=0.0003), age at HIV diagnosis (HR=1.73, 95% CI: 1.25-2.39, p=0.0010), and black race (HR=2.07, 95% CI: 1.58-2.72, p<.0001). History of alcohol abuse (HR=0.54, 95% CI: 0.39-0.75, p=0.0002), longer time with well-controlled infection (HR=0.63, 95% CI: 0.59-0.67, p<.0001), and receiving integrase inhibitors (HR=0.64, 95% CI: 0.45-0.92, p=0.041) were associated with reduced risk. Several risk factors included in the multivariable model, such as PSA testing, testosterone levels, and maximum BMI, were not found to be significantly associated with or protective for prostate cancer. (d) Further research is needed to confirm our findings and to better identify sub-groups of well-controlled HIV-positive men at greatest increased prostate cancer risk. Citation Format: Kathryn E. Royse, Jose M. Garcia, Donna L. White, Jennifer R. Kramer, Yongquan Dong, Suchismita Raychaudhury, Peter A. Richardson, Christine Hartman, Elizabeth Y. Chiao. Prostate adenocarcinoma incidence and risk factors in Veterans with well controlled HIV infection [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5044.

Obesity has reached epidemic proportions in the U.S. and is more prevalent in Veterans. Obesity and obesity-related comorbidities are also very common in HIV-infected individuals and HIV- and antiretroviral therapy (ART)-specific factors may contribute to obesity and to the excess morbidity and mortality seen in this population. Our objective was to evaluate the weight trajectory in a retrospective cohort of HIV-infected and HIV-uninfected veterans. We also sought to establish the role of ART in this setting. HIV-infected (n=31,015, 97% male, 36% Caucasian, 52% African American, age 48±11 years) and HIV-uninfected veterans (controls, n=105,801, 96% male, 63% Caucasian, 19% African American, age 48±12 years) were included in the analyses. Variables of interest including body weight, weight change at 1, 2 and 5 years after diagnosis (or corresponding baseline visit for controls), ART use and other covariates (age, race, gender). Data were extracted from the VA Corporate Data Warehouse using laboratory values, medications, vital signs and ICD codes. Body weight at baseline was lower in HIV-infected veterans compared to controls (80±17.7 vs. 92.2±19.9 Kg respectively, p<0.01), and the prevalence of overweight (BMI 25-29.9) and obesity (BMI≥30) was higher in controls (34% and 17% in HIV-infected, 38% and 41% in controls respectively). HIV-infected individuals with a BMI <25 gained more weight at 1, 2 and 5 years post-index date compared to controls with most of these gains taking place at year 1 (3.4±7.8 vs. 2.2±7.1 Kg, 3.9±8.6 vs. 3±8 Kg, 4.4±9.8 vs. 4±9.1 Kg change from baseline at 1, 2 and 5 years respectively, all p<0.01). Although this trend was reversed in overweight individuals at 5 years (1.1±7.1 vs. 0.9±5.6 Kg, p=0.06; 1.3±8.1 vs. 1.4±6.5 Kg, p=0.22; 1.7±9.7 vs. 2.3±8.4 Kg, p<0.01 respectively) and in obese individuals at 2 and 5 years (-0.15±9.7 vs. -0.14±8.2 Kg, p>0.9; -0.29±11.2 vs. 0.19±9.2 Kg, p<0.01; -0.03±13 vs. 1.06±11.6 Kg, p<0.01 respectively). Among HIV-infected individuals, those on ART (n=16,028) gained more weight compared to those not on ART (n=4,392) 1, 2 and 5 years after diagnosis (2.3±8.2 vs. 0.88±7.5 Kg, 2.5±9.1 vs. 1.03±8.9 Kg, 2.8±10.6 vs. 1.65±10.2 Kg, respectively, all p<0.01). The weight increase at 1 year was 2.3±8.2 Kg for those exposed to nucleoside reverse-transcriptase inhibitors (NRTI, n=15,853), 2.2±8 Kg for non-NRTI (n=9,237), 2.7±8.6 Kg for protease inhibitors (n=6,961), 2.8±8.2 Kg for integrase inhibitors (n=1895), 0.01±7.1 Kg for fusion inhibitors (n=50), 2.1±8.4 Kg for CCR5 antagonists (n=63) and 2.4±8.8 Kg for pharmacokinetic enhancers (n=499). HIV infection in veterans is associated with lower rates of obesity at diagnosis and significant weight gain for those with a BMI<25 post-diagnosis. Our data also suggest that exposure to ART (perhaps with the exception of fusion inhibitors) is likely to mediate the increase in body weight seen in this setting.

Background: To evaluate the risks of esophageal and stomach carcinomas in people living with HIV (PLWH) compared with the general population and risk factors for these cancers in PLWH. Setting: Retrospective cohort study in the Veterans Health Administration. Methods: We compared incidence rates for esophageal and stomach cancers in 44,075 HIV-infected male veterans with those in a matched HIV-uninfected cohort (N = 157,705; 4:1 matched on age and HIV-index date). We used Cox regression models to estimate Hazard ratios (HRs) and 95% confidence intervals (CIs) for associations with HIV infection and for cancer risk factors in PLWH. Results: In unadjusted models, HIV infection was associated with increased risks of esophageal squamous cell carcinoma (ESCC; HR, 2.21; 95% CI: 1.47 to 3.13) and gastric cardia cancer (HR, 1.69; 95% CI: 1.00 to 2.85) but associated with lower risk of esophageal adenocarcinoma (EAC; HR, 0.48; 95% CI: 0.31 to 0.74). After adjusting for age, race/ethnicity, smoking and alcohol use, HIV infection remained statistically significantly associated with elevated risk for ESCC [adjusted hazard ratio (aHR), 1.58; 95% CI: 1.02 to 2.47], especially among HIV-infected patients with CD4 count ≤200 (aHR, 2.20; 95% CI: 1.35 to 3.60). HIV infection was not associated with risks of EAC (aHR, 0.82; 95% CI: 0.53 to 1.26), gastric cardia (aHR, 0.80; 95% CI: 0.33 to 1.94), or noncardia (aHR, 1.06; 95% CI: 0.61 to 1.84) cancers. Risk factors for these cancers in HIV-infected patients were otherwise similar to those in general population (eg, Helicobacter pylori for gastric noncardia cancer). Conclusion: HIV-infected individuals with low CD4 count are at highest risk for ESCC, but HIV infection was not independently associated with EAC or gastric cancer after adjusting for confounders.

Nivolumab is a standard treatment option in several advanced malignancies, but safety and efficacy are still unknown in patients with human immunodeficiency virus (HIV) infection. We describe a case series of people living with HIV (PLWH) receiving nivolumab in the Veterans Health Administration (VA) and report responses and toxicities. We identified all PLWH who received nivolumab at any VA facility since 2000 in the Corporate Data Warehouse (CDW), which provides nationwide research access to VA electronic medical records. We identified 16 HIV-infected nivolumab recipients. The median number of nivolumab doses received was 6 (range, 1-32). Changes in CD4 count during therapy were variable, with 70% (7/10) of patients experiencing increases. Half of PLWH were treated for non-small-cell lung cancer; 2 for Hodgkin lymphoma (HL), 2 for renal cell carcinoma, and 4 for off-label cancers. For non-small-cell lung cancer, 7 patients had evaluable responses. Although 5 of 7 patients immediately progressed, 1 had a partial response and 1 had stable disease, which were both durable. Two of 16 (14%) PLWH had complete responses; both with HL (2/2 HL, 100%). The prevalence of immune-related adverse effects was 40% overall (6/15); 27% (4/15) had pneumonitis. To our knowledge, this is the largest case series reporting outcomes with nivolumab in PLWH. Outcomes were comparable with those seen in studies of HIV-uninfected patients, and particularly interesting for HL. The reason for the high proportions of immune-related adverse effects is unclear, but needs to be confirmed in larger studies.

Abstract The objective of this study was to compare the efficacy and safety of nivolumab in the HIV-infected and HIV-uninfected veteran populations. WHAT IS NEW: Most clinical trials highlighting checkpoint inhibitors excluded people living with HIV (PLWH). This is the first study to report equivalent nivolumab tumor response rates in PLWH, but higher rates of pneumonitis.METHODS: We searched the Corporate Data Warehouse (CDW) to identify all HIV-positive patients who used the Veterans Health Administration (VA) between 2000 and 2016. For this cohort of 46,916 PLWH, we obtained a 4:1 age-matched HIV-negative control cohort. We used pharmacy database to identify all nivolumab recipients through July 26, 2017. We reviewed patients' electronic medical records using Compensation and Pension Records Interchange (CAPRI) to obtain age, sex, geographic location, cancer type, number of nivolumab doses received, previous cancer therapy, adverse events, and response to therapy. We calculated summary descriptive measures for both groups and compared the proportion of patients experiencing adverse event or pneumonitis in groups by HIV status, using chi-square or Fisher's exact test. RESULTS: Sixteen PLWH and 68 HIV-negative controls received nivolumab during the study period. Only 51 controls had accessible data. Median age at nivolumab initiation was 65 years in both groups (range, 47-85 [IQR, 59-68] in PLWH; range, 42-79 [IQR 59-68] in controls); all patients were male. Overall, 63% received nivolumab for non-small cell lung cancer (NSCLC): 8/16 (50%) in PLWH, 34/51 (67%) in controls. Other indications in PLWH included renal cell carcinoma (RCC) (2/16 [13%]), Hodgkin lymphoma (HL) (2/16 [13%]), hepatocellular carcinoma (HCC) (2/16 [13%]). Other indications in controls were RCC (9/51 [18%]), melanoma (5/51, [10%]), and head and neck squamous cell carcinoma (3/51 [6%]).Regardless of HIV status, the median number of prior lines of therapy was 1, median number of nivolumab doses received was 6, and median progression-free survival (PFS) in NSCLC was 2.75 months. Half of each NSCLC group received radiation; fewer PLWH had COPD (50%, vs. 82% of controls). PLWH had a trend towards more adverse events (AEs) (6/15 [40%], vs. 13/51 [26%] of controls, p=0.28). A significantly higher proportion of PLWH experienced pneumonitis (4/15 [27%], vs. 2/51 [4%] of controls, p=0.007).Other AEs among PLWH were rash, hypothyroidism, and autoimmune diabetes mellitus. Other AEs among controls were fatigue, colitis, rash, hypothyroidism, arthritis, and hepatitis (1-3 patients each). CONCLUSION: Among veteran PLWH, rates of nivolumab administration, and PFS in NSCLC, were comparable to those of HIV-uninfected counterparts. Pneumonitis was significantly more frequent in PLWH. Further studies should investigate the mechanism of pneumonitis in this population, confirm the high frequency in larger cohorts of PLWH, and identify clinical risk factors for pneumonitis. Citation Format: Elaine Chang, Aaron P. Thrift, Donna L. White, Jennifer Kramer, Anita L. Sabichi, Christine Hartman, Kathryn E. Royse, Peter A. Richardson, Elizabeth Y. Chiao. Nivolumab efficacy and safety in veterans with and without HIV infection [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 617.

Objectives: Veterans have an increased risk of laryngeal cancer, yet their oncologic and functional outcomes remain understudied. We sought to determine the longitudinal impact of tracheoesophageal puncture and voice prosthesis on quality-of-life measures in veterans following total laryngectomy (TL). Methods: We performed a cross-sectional analysis of TL patients (n = 68) treated at the Michael E. DeBakey Veterans Affairs Medical Center using the Voice Handicap Index (VHI), MD Anderson Dysphagia Index (MDADI), and University of Washington Quality of Life Index (UW-QOL). Results: Using tracheoesophageal (TE) speech was associated with significantly better VHI, MDADI, and UW-QOL scores compared to other forms of communication. The association between TE speech use on VHI, MDADI, and UQ-QOL persisted even when the analysis was limited to patients with >5-year follow-up and was maintained on multivariate analysis that accounted for a history of radiation and laryngectomy for recurrent laryngeal cancer. Conclusions: Using tracheoesophageal speech after total laryngectomy is associated with durable improvements in quality of life and functional outcomes in veterans. Tracheoesophageal voice restoration should be attempted whenever technically feasible in patients that meet the complex psychosocial and physical requirements to appropriately utilize TE speech.

OBJECTIVE:To evaluate HIV-related and other clinical risk factors associated with oropharynx cancer (OPSCC) in HIV-infected U.S. Veterans. METHODS:Retrospective cohort study utilizing Veterans Affairs HIV Clinical Case Registry (CCR) data from 1985 to 2010. Outcome was incident OPSCC as indicated by 1 inpatient or 2 outpatient ICD-9 codes. Cox proportional hazard models were used to determine hazard ratios (HR) and 95% confidence intervals (CI) for each risk factor on the time to OPSCC diagnosis. RESULTS:A total of 40,996 HIV-infected male veterans were included in the cohort with 97 cases of OPSCC. The age adjusted incidence rate was 23.2/100,000 [95% CI 17.8-29.2]. Age>50 (aHR=3.8, 95% CI 1.9-7.8), recent CD4<200 (aHR=3.8, 95% CI 2.0-7.3), and undetectable HIV viral loads 40-79% of the time (aHR=1.8, 95% CI 1.1-3.0) were associated with an increased risk of OPSCC. Era of HIV diagnosis, utilization of cART, nadir CD4 count, race, smoking history, and previous risk of HPV disease, including condyloma or invasive squamous cell carcinoma of the anus (SCCA) were not associated with increased risk of OPSCC. CONCLUSION:Patients who were older at beginning of follow up, had lower CD4 counts around the time of OPSCC diagnosis, and moderate HIV viral control during follow-up had an increased risk of OPSCC. Other HPV-related diseases such as SCCA and condyloma did not increase the risk for OPSCC.

Background: The hospital setting provides an opportunity to re-engage people living with HIV (PLWH) in HIV care. We developed and implemented a protocol to identify PLWH in a hospital setting. The aim of the current study was to report on our strategy to recruit hospitalized HIV patients into an intervention study, and to report on lessons learned for future studies.Methods: Our protocol was developed based on experience of our research staff in recruiting HIV patients as well as clinical input from providers and administrators on delivering care in hospitalized settings. We identified hospitalized PLWH between 2010 and 2013 who were potentially eligible for an intervention study. Patients were identified by review of electronic medical records and clinician referral, followed by in-person screening to confirm eligibility. We examined factors related to identifying and enrolling hospitalized patients, and documented lessons learned.Results: Key strategies included systematic medical record review followed by in-person screening, collaboration with staff, and flexibility in recruitment logistics. We identified 1801 PLWH hospitalized during the 3-year study period. Eighty-four percent (n=1514) met the met the inclusion criteria based on medical record review. Of these, 48% (n=733) were ineligible. Among eligible patients, 59% (n=460) were enrolled. Only 3% (n=23) of eligible patients declined; 84% (n=321) were not enrolled because they were discharged before enrollment. Lessons learned included (1) needing to identify patients and deliver the intervention before hospital discharge, (2) limiting the complexity of the intervention, and (3) having research staff available on weekends and after hours.Conclusions: Targeted recruitment of hospitalized populations is a feasible and productive approach for finding and engaging PLWH who are newly diagnosed or out of routine care.

OBJECTIVE:Geographic and racial disparities may contribute to variation in the incidence and outcomes of HIV-associated cancers in the United States.METHOD:Using the Surveillance, Epidemiology, and End Results (SEER) database, we analyzed Kaposi sarcoma (KS) incidence and survival by race and geographic region during the combined antiretroviral therapy era. Reported cases of KS in men from 2000 to 2013 were obtained from 17 SEER cancer registries. Overall and age-standardized KS incidence rates were calculated and stratified by race and geographic region. We evaluated incidence trends using joinpoint analyses and calculated adjusted hazard ratios (aHR) for overall and KS-specific mortality using multivariable Cox proportional hazards models.RESULTS:Of 4,455 KS cases identified in men younger than 55 years (median age 40 years), the annual percent change (APC) for KS incidence significantly decreased for white men between 2001 and 2013 (APC -4.52, p = 0.02). The APC for AA men demonstrated a non-significant decrease from 2000-2013 (APC -1.84, p = 0.09). Among AA men in the South, however, APC has significantly increased between 2000 and 2013 (+3.0, p = 0.03). In addition, compared with white men diagnosed with KS during the same time period, AA men were also more likely to die from all causes and KS cancer-specific causes (aHR 1.52, 95% CI 1.34-1.72, aHR 1.49, 95% CI 1.30-1.72 respectively).CONCLUSION:Although overall KS incidence has decreased in the U.S., geographic and racial disparities in KS incidence and survival exist.