Incidence of Colon Cancer Among Medicaid Beneficiaries With or Without Human Immunodeficiency Virus Under Comparable Colorectal Cancer Screening Patterns.

Background: People with human immunodeficiency virus (HIV; PWH) in the United States have a lower incidence of colon cancer than the general population. The lower incidence may be explained by differences in receipt of screening. Thus, we sought to estimate colon cancer incidence under scenarios in which Medicaid beneficiaries, with or without HIV, followed the same screening protocols. Methods: We used data from 1.5 million Medicaid beneficiaries who were enrolled in 14 US states in 2001-2015 and aged 50-64 years; 72 747 beneficiaries had HIV. We estimated risks of colon cancer and death by age, censoring beneficiaries when they deviated from 3 screening protocols, which were based on Medicaid's coverage policy for endoscopies during the time period, with endoscopy once every 2, 4, or 10 years. We used inverse probability weights to control for baseline and time-varying confounding and informative loss to follow-up. Analyses were performed overall, by sex, and by race/ethnicity. Results: PWH had a lower incidence of colon cancer than beneficiaries without HIV. Compared with beneficiaries without HIV, the risk difference at age 65 years was -1.6% lower (95% confidence interval, -2.3% to -.7%) among PWH with the 2-year protocol and -0.8% lower (-1.3% to -.3%) with the 10-year protocol. Results were consistent across subgroup and sensitivity analyses. Conclusions: Our findings suggest that the lower risk of colon cancer that has been observed among PWH aged 50-64 years compared with those without HIV is not due to differences in receipt of lower endoscopy. Keywords: colon cancer, colorectal cancer screening, endoscopy, Medicaid, human immunodeficiency virus.

Retention in care and antiretroviral therapy adherence among Medicaid beneficiaries with HIV, 2001-2015.

Disparities in HIV care by socioeconomic status, place of residence, and race/ethnicity prevent progress toward epidemic control. No study has comprehensively characterized the HIV care cascade among people with HIV enrolled in Medicaid - an insurance source for low-income individuals in the US. We analyzed data from 246,127 people with HIV enrolled in Medicaid 2001-2015, aged 18-64, living in 14 US states. We estimated monthly prevalence of four steps of the care cascade: retained in care/adherent to ART; retained/not adherent; not retained/adherent; not retained/not adherent. Beneficiaries were retained in care if they had an outpatient care encounter every six months. Adherence was based on medication possession ratio. We estimated prevalence using a non-parametric multi-state approach, accounting for death as a competing event and for Medicaid disenrollment using inverse probability of censoring weights. Across 2001-2015, the proportion of beneficiaries with HIV who were retained/ART adherent increased, overall and in all subgroups. By 2015, approximately half of beneficiaries were retained in care, and 42% of beneficiaries were ART adherent. We saw meaningful differences by race/ethnicity and region. Our work highlights an important disparity in the HIV care cascade by insurance status during this time period.

Lower endoscopy, early-onset, and average-onset colon cancer among Medicaid beneficiaries with and without HIV.

BACKGROUND: Studies suggest a lower colorectal cancer (CRC) risk and lower or similar CRC screening among people with HIV (PWH) compared with the general population. We evaluated the incidence of lower endoscopy and average-onset (diagnosed at ≥50) and early-onset (diagnosed at <50) colon cancer by HIV status among Medicaid beneficiares with comparable sociodemographic factors and access to care. METHODS: We obtained Medicaid Analytic eXtract (MAX) data from 2001 to 2015 for 14 states. We included 41 727 243 and 42 062 552 unique individuals with at least 7 months of continuous eligibility for the endoscopy and colon cancer analysis, respectively. HIV and colon cancer diagnoses and endoscopy procedures were identified from inpatient and other nondrug claims. We used Cox proportional hazards regression models to assess endoscopy and colon cancer incidence, controlling for age, sex, race/ethnicity, calendar year and state of enrollment, and comorbidities conditions. RESULTS: Endoscopy and colon cancer incidence increased with age in both groups. Compared with beneficiaries without HIV, PWH had an increased hazard of endoscopy; this association was strongest among those 18-39 years [hazard ratio: 1.85, 95% confidence interval (95% CI) 1.77-1.92] and attenuated with age. PWH 18-39 years also had increased hazard of early-onset colon cancer (hazard ratio: 1.66, 95% CI:1.05-2.62); this association was attenuated after comorbidity adjustment. Hazard ratios were null among all beneficiaries less than 50 years of age. PWH had a lower hazard of average-onset colon cancer compared with those without HIV (hazard ratio: 0.79, 95% CI: 0.66-0.94). CONCLUSION: PWH had a higher hazard of endoscopy, particularly at younger ages. PWH had a lower hazard of average-onset colon cancer. Early-onset colon cancer was higher among the youngest PWH but not associated with HIV overall.

Comparing Cancer Incidence in an Observational Cohort of Medicaid Beneficiaries With and Without HIV, 2001-2015.

BACKGROUND: Life expectancy among people with HIV (PWH) is increasing, making chronic conditions-including cancer-increasingly relevant. Among PWH, cancer burden has shifted from AIDS-defining cancers (ADCs) toward non-AIDS-defining cancers (NADCs). SETTING: We described incidence of cancer in a claims-based cohort of Medicaid beneficiaries. We included 43,426,043 Medicaid beneficiaries (180,058 with HIV) from 14 US states, aged 18-64, with >6 months of enrollment (with no dual enrollment in another insurance) and no evidence of a prveious cancer. METHODS: We estimated cumulative incidence of site-specific cancers, NADCs, and ADCs, by baseline HIV status, using age as the time scale and accounting for death as a competing risk. We compared cumulative incidence across HIV status to estimate risk differences. We examined cancer incidence overall and by sex, race/ethnicity, and calendar period. RESULTS: PWH had a higher incidence of ADCs, infection-related NADCs, and death. For NADCs such as breast, prostate, and colon cancer, incidence was similar or higher among PWH below age 50, but higher among those without HIV by age 65. Incidence of lung and head and neck cancer was always higher for female beneficiaries with HIV, whereas the curves crossed for male beneficiaries. We saw only small differences in incidence trends by race/ethnicity. CONCLUSION: Our findings suggest an increased risk of certain NADCs at younger ages among PWH, even when compared against other Medicaid beneficiaries, and highlight the importance of monitoring PWH for ADCs and NADCs. Future work should explore possible mechanisms explaining the differences in incidence for specific cancer types.

The reliability and validity of lung cancer and melanoma clinical quality survival measures.

OBJECTIVE: To develop a risk adjustment approach and test reliability and validity for oncology survival measures. DATA SOURCES AND STUDY SETTING: We used the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER)-Medicare data from 2010 to 2013, with mortality data through 2015. STUDY DESIGN: We developed 2-year risk-standardized survival rates (RSSR) for melanoma, non-small cell lung cancer (NSCLC), and small cell lung cancer (SCLC). Patients were attributed to group practices based on the plurality of visits. We identified the risk-adjustment variables via bootstrap and calculated the RSSRs. Reliability was tested via three approaches: (1) signal-to-noise ratio (SNR) reliability, (2) split-half, and (3) test-retest using bootstrap. We tested known group validity by stage at diagnosis using Cohen's d. DATA COLLECTION/EXTRACTION METHODS: We selected all patients enrolled in Medicare and linked to SEER during the measurement period with an incident first primary diagnosis of stage I-IV melanoma, NSCLC, or SCLC. We excluded patients with missing data on month and/or stage of diagnosis. PRINCIPAL FINDINGS: Results are based on patients with melanoma (n = 4344); NSCLC (n = 16,080); and SCLC (n = 2807) diagnosed between 2012 and 2013. The median (interquartile range) for the RSSRs at the group practice-level were 0.89 (0.83-0.87) for melanoma, 0.37 (0.30-0.43) for NSCLC, and 0.19 (0.11-0.25) for SCLC. C-statistics for the models ranged from 0.725 to 0.825. The reliability varied by approach with median SNR 0.20, 0.25, and 0.13; median test-retest 0.59, 0.57, and 0.56; median split-half reliability 0.21, 0.29, and 0.29 for melanoma, NSCLC, and SCLC, respectively. Cohen's d for stage I-IIIa and IIIb+ was 1.27, 0.86, 0.60 for melanoma, NSCLC, and SCLC, respectively. CONCLUSIONS: Our results suggest that these cancer survival measures demonstrated adequate test-retest reliability and expected findings for the known-group validity analysis. If data limitations and feasibility challenges can be addressed, implementation of these quality measures may provide a survival metric used for oncology quality improvement efforts.

A comparison of cancer stage at diagnosis and treatment initiation between enrollees in an urban HIV clinic and SEER.

PURPOSE: A comparison of stage at cancer diagnosis and cancer treatment rates between people with HIV (PWH) and the general US population is needed to identify any disparities by HIV status. METHODS: We compared 236 PWH in clinical care diagnosed with cancer from 1997 to 2014 to a sample from NCI's Surveillance, Epidemiology and End Results (SEER) Program, presumed to be HIV negative. We performed G-computation using random forest methods to estimate stage and treatment percent differences (PD) by HIV. We conducted sensitivity analyses among non-AIDS-defining cancers (NADC), by sex and by CD4 ≤ 200 or > 200 cells/mm3. RESULTS: PWH were less likely to be diagnosed at localized stage (PD = - 16%; 95% CI - 21, - 11) and more likely to be diagnosed at regional stage (PD = 14%; 95% CI 8, 19) than those in SEER. Cancer treatment rates were 13% lower among PWH as compared to SEER (95% CI - 18, - 8). The difference in percent receiving cancer treatment was more pronounced for those with lower CD4 at cancer diagnosis (PD -15%; 95% CI - 27, - 6). Lower treatment rates were observed among NADC, males, and women with CD4 ≤ 200. CONCLUSION: Cancer care for PWH could be improved by diagnosis at earlier stages and increasing rates of cancer treatment.

Immune Status and Associated Mortality After Cancer Treatment Among Individuals With HIV in the Antiretroviral Therapy Era.

Importance: Immunologic decline associated with cancer treatment in people with HIV is not well characterized. Quantifying excess mortality associated with cancer treatment-related immunosuppression may help inform cancer treatment guidelines for persons with HIV. Objective: To estimate the association between cancer treatment and CD4 count and HIV RNA level in persons with HIV and between posttreatment CD4 count and HIV RNA trajectories and all-cause mortality. Design, Setting, and Participants: This observational cohort study included 196 adults with HIV who had an incident first cancer and available cancer treatment data while in the care of The Johns Hopkins HIV Clinic from January 1, 1997, through March 1, 2016. The study hypothesized that chemotherapy and/or radiotherapy in people with HIV would increase HIV RNA levels owing to treatment tolerability issues and would be associated with a larger initial decline in CD4 count and slower CD4 recovery compared with surgery or other treatment. An additional hypothesis was that these CD4 count declines would be associated with higher mortality independent of baseline CD4 count, antiretroviral therapy use, and risk due to the underlying cancer. Data were analyzed from December 1, 2017, through April 1, 2018. Exposures: Initial cancer treatment category (chemotherapy and/or radiotherapy vs surgery or other treatment). Main Outcomes and Measures: Post-cancer treatment longitudinal CD4 count, longitudinal HIV RNA level, and all-cause mortality. Results: Among the 196 participants (135 [68.9%] male; median age, 50 [interquartile range, 43-55] years), chemotherapy and/or radiotherapy decreased initial CD4 count by 203 cells/µL (95% CI, 92-306 cells/µL) among those with a baseline CD4 count of greater than 500 cells/µL. The decline for those with a baseline CD4 count of no greater than 350 cells/µL was 45 cells/µL (interaction estimate, 158 cells/µL; 95% CI, 31-276 cells/µL). Chemotherapy and/or radiotherapy had no detrimental association with HIV RNA levels. After initial cancer treatment, every 100 cells/µL decrease in CD4 count resulted in a 27% increase in mortality (hazard ratio, 1.27; 95% CI, 1.08-1.53), adjusting for HIV RNA level. No significant increase in mortality was associated with a unit increase in log10 HIV RNA after adjusting for CD4 count (hazard ratio, 1.24; 95% CI, 0.94-1.65). Conclusions and Relevance: In this study, chemotherapy and/or radiotherapy was associated with significantly reduced initial CD4 count in adults with HIV compared with surgery or other treatment. Lower CD4 count after cancer treatment was associated with an increased hazard of mortality. Further research is necessary on the immunosuppressive effects of cancer treatment in adults with HIV and whether health care professionals must consider the balance of cancer treatment efficacy against the potential cost of further immunosuppression. Monitoring of immune status may also be helpful given the decrease in CD4 count after treatment and the already immunocompromised state of patients with HIV.

Short Communication: Differences in 5-Year Survival After Cancer Diagnosis Between HIV Clinic Enrollees and the General U.S. Population.

A total of 236 people with HIV (PWH) with cancer diagnosed between 1997 and 2014 in the Johns Hopkins HIV Clinical Cohort (JHHCC) were compared with a sample from NCI's Surveillance, Epidemiology, and End Results (SEER) Program, presumed to be HIV negative. Using G-computation with random survival forest methods, we estimated 5-year restricted mean survival time (RMST) differences by HIV status. Sensitivity analyses were performed among non-AIDS defining cancers, males, females, and stratifying PWH by CD4 ≤ 200 or >200 cells/mm3 at cancer diagnosis. PWH with CD4 ≤ 200 cells/mm3 had decreased survival compared with those in SEER (-7 months; 95% CI = -13 to -2). Women with HIV and CD4 ≤ 200 cells/mm3 at cancer diagnosis had lower survival than SEER women (-10 months; 95% CI = -18 to -2). In the total population, there was no significant difference in 5-year RMST; however, women with HIV and low CD4 had higher mortality despite accounting for stage at diagnosis and first course of cancer treatment.

Do Symptoms of Depression Interact with Substance Use to Affect HIV Continuum of Care Outcomes?

Few studies examine how depression and substance use interact to affect HIV control. In 14,380 persons with HIV (PWH), we used logistic regression and generalized estimating equations to evaluate how symptoms of depression interact with alcohol, cocaine, opioid, and methamphetamine use to affect subsequent retention in care, maintaining an active prescription for ART, and consistent virologic suppression. Among PWH with no or mild depressive symptoms, heavy alcohol use had no association with virologic suppression (OR 1.00 [0.95-1.06]); among those with moderate or severe symptoms, it was associated with reduced viral suppression (OR 0.80 [0.74-0.87]). We found no interactions with heavy alcohol use on retention in care or maintaining ART prescription or with other substances for any outcome. These results highlight the importance of treating moderate or severe depression in PWH, especially with comorbid heavy alcohol use, and support multifaceted interventions targeting alcohol use and depression.

An application of restricted mean survival time in a competing risks setting: comparing time to ART initiation by injection drug use.

BACKGROUND: Restricted mean survival time (RMST) is an underutilized estimand in time-to-event analyses. Herein, we highlight its strengths by comparing time to (1) all-cause mortality and (2) initiation of antiretroviral therapy (ART) for HIV-infected persons who inject drugs (PWID) and persons who do not inject drugs. METHODS: RMST to death was determined by integrating the Kaplan-Meier survival curve to 5 years of follow-up. To account for the competing risks of death and loss-to-clinic when estimating time to ART, we calculated RMST to ART initiation by estimating the area between the survival curve for ART initiation and the cumulative incidence curve for death or loss-to-clinic. We standardized all curves using inverse probability of exposure weights. RESULTS: We followed 3044 HIV-positive, ART-naive persons from enrollment into the Johns Hopkins HIV Clinical Cohort from 1996 to 2014. PWID had a - 0.19 year (95% confidence interval (CI): - 0.29, - 0.10) difference in survival over 5 years of follow-up compared to persons who did not inject drugs. There was no difference between the two groups in time not on ART while alive and in clinic (RMST difference = 0.08, 95% CI: -0.10, 0.36). CONCLUSIONS: PWID have similar expected time to ART initiation after properly accounting for their greater risk of death and loss-to-clinic.

Influence of Injection Drug Use-Related HIV Acquisition on CD4 Response to First Antiretroviral Therapy Regimen Among Virally Suppressed Individuals.

BACKGROUND: The inflammatory effects of injection drug use (IDU) may result in an impaired immune response to antiretroviral therapy (ART). We examined CD4 response to first ART regimen among individuals in routine HIV care, stratified by IDU-related HIV acquisition. SETTING: Cohort study including patients who initiated ART between 2000 and 2015 in the Johns Hopkins HIV Clinic. METHODS: We followed individuals from ART initiation until death, loss to follow-up, loss of viral load suppression (<500 copies/mL), or administrative censoring. We described CD4 trajectories after ART initiation using inverse probability weighted quantile regression models with restricted cubic splines for time. Weights accounted for differences in baseline characteristics of persons comparing those with IDU-related HIV acquisition to those with other HIV acquisition risks (non-IDU) and possible nondifferential censoring due to death, loss to follow-up, or loss of viral load suppression. We also examined CD4 response by strata of CD4 at ART initiation (≤200, 201-350, >350). RESULTS: Of 1244 patients initiating ART, 30.4% were IDU. Absolute CD4 cell difference at the 50th percentile comparing IDU with non-IDU was -25 cells [95% confidence interval (CI): -63 to 35], -66 cells (95% CI: -141 to 16), and -91 cells (95% CI: -190 to -5) at 2, 4, and 6 years after ART initiation, respectively. Results were similar (non-IDU with slightly higher CD4 count, but not statistically significant differences) at other percentiles and stratified by baseline CD4. CONCLUSIONS: CD4 recovery after ART initiation was similar for IDU and non-IDU, conditional on consistent viral load suppression.

Race-based differences in length of stay among patients undergoing pancreatoduodenectomy.

BACKGROUND: Race-based disparities in operative morbidity and mortality have been demonstrated for various procedures, including pancreatoduodenectomy (PD). Race-based differences in hospital length-of-stay (LOS), especially related to provider volume at the surgeon and hospital level, remain poorly defined. METHODS: Using the 2003-2009 Nationwide Inpatient Sample, we determined year-specific PD volumes for surgeons and hospitals and grouped them into terciles. Patient race (white, black, or Hispanic), age, sex, and comorbidities were examined. Median length of stay was calculated, and multivariable logistic regression was used to examine factors associated with increased LOS. RESULTS: Among 4,319 eligible individuals, 3,502 (81.1%) were white, 423 (9.8%) were black, and 394 (9.1%) were Hispanic. Overall median LOS was 12 days (range, 0-234). Median annual surgeon volume was 8 (interquartile range [IQR], 2-19; range, 1-54). Annual hospital volume ranged from 1 to 129 (median, 19; IQR, 7-55). White patients were more likely to have been treated at medium- to high-volume hospitals (odds ratio [OR] 1.53, P < .001) and by medium- to high-volume surgeons (OR 1.62, P < .001) than black or Hispanic patients. After PD, white, black, and Hispanic patients demonstrated similar in-hospital mortality (5.1%, 5.7% and 7.2% respectively P = .250). After adjustment, black (OR 1.36, P = .010) and Hispanic (OR 1.68, P < .001) patients were more likely to have a greater LOS after PD. CONCLUSION: Black and Hispanic PD patients were less likely than white patients to be treated at higher-volume hospitals and by higher-volume surgeons. Proportional mortality and LOS after PD were greater among black and Hispanic patients.