by
Lesley S. Park;
Janet P. Tate;
Keith Sigel;
David Rimland;
Kristina Crothers;
Cynthia Gibert;
Maria C. Rodriguez-Barradas;
Matthew Bidwell Goetz;
Roger J. Bedimo;
Sheldon T. Brown;
Amy C. Justice;
Robert Dubrow
Objective: 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.
Design: Prospective cohort study.
Methods: 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 and incidence rate ratios (IRR, HIV+ versus uninfected) over four calendar periods with incidence rate and IRR period trend P values for cancer groupings and specific cancer types.
Results: We observed 3714 incident cancer diagnoses in HIV+ and 5760 in uninfected persons. The HIV+ all-cancer crude incidence rate increased between 1997–2000 and 2009–2012 (P trend = 0.0019). However, after standardization, we observed highly significant HIV+ incidence rate declines for all cancer (25% decline; P trend <0.0001), AIDS-defining cancers (55% decline; P trend <0.0001), nonAIDS-defining cancers (NADC; 15% decline; P trend = 0.0003), and nonvirus-related NADC (20% decline; P trend <0.0001); significant IRR declines for all cancer (from 2.0 to 1.6; P trend <0.0001), AIDS-defining cancers (from 19 to 5.5; P trend <0.0001), and nonvirus-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).
Conclusion: Improved HIV care resulting in improved immune function most likely contributed to the HIV+ incidence rate 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.
by
E. Jennifer Edelman;
Stephen A. Maisto;
Nathan B. Hansen;
Christopher J. Cutter;
James Dziura;
Lynn E. Fiellin;
Patrick G. O'Connor;
Roger Bedimo;
Cynthia Gibert;
Vincent Marconi;
David Rimland;
Maria C. Rodriguez-Barradas;
Michael S. Simberkoff;
Amy C. Justice;
Kendall J. Bryant;
David A. Fiellin
Unhealthy alcohol use is common among HIV-positive patients, yet effective evidence-based treatments are rarely provided in clinical settings providing HIV care. Further, given patient variability in response to initial treatments, stepped care approaches may be beneficial. We describe the rationale, aims and study design for the current Starting Treatment for Ethanol in Primary care Trials (STEP Trials); three parallel randomized controlled effectiveness trials being conducted in five Infectious Disease Clinics. Participants meeting criteria for: 1) at-risk drinking, 2) moderate alcohol use with liver disease (MALD), or 3) alcohol use disorder (AUD) are randomized to integrated stepped care versus treatment as usual. For those with at-risk drinking or MALD, integrated stepped care starts with a one session brief intervention and follow-up 2-week telephone booster. Based on pre-specified nonresponse criteria, participants may be “stepped up” at week 4 to receive four sessions of motivational enhancement therapy (MET) and “stepped up” again at week 12 for addiction physician management (APM) and consideration of alcohol pharmacotherapy. For those with AUD, integrated stepped care begins with APM. Non-responders may be “stepped up” at week 4 to receive MET and again at week 12 for a higher level of care (e.g. intensive outpatient program). The primary outcome is alcohol consumption assessed at 24 weeks, and secondary outcome is the VACS Index, a validated measure of HIV morbidity and mortality risk. Results from the STEP Trials should inform future research and the implementation of interventions to address unhealthy alcohol use among HIV-positive individuals.
by
Julie A. Womack;
Terrence E. Murphy;
Harini Bathulapalli;
Kathleen M. Akgun;
Cynthia Gibert;
Ken M. Kunisaki;
David Rimland;
Maria Rodriguez-Barradas;
H. Klar Yaggi;
Amy C. Justice;
Nancy S. Redeker
by
Keith Sigel;
Juan Wisnivesky;
Kirsha Gordon;
Robert Dubrow;
Amy Justice;
Sheldon T. Brown;
Joseph Goulet;
Adeel A. Butt;
Stephen Crystal;
David Rimland;
Maria Rodriguez-Barradas;
Cynthia Gibert;
Lesley Park;
Kristina Crothers
Background: 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. Design: 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. Methods: 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. Results: 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. Conclusion: 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.
by
Janet P. Tate;
Sheldon Brown;
Cynthia Gibert;
Matthew Goetz;
Vincent Marconi;
Kris Ann Oursler;
David Rimland;
Maria Rodriguez-Barradas;
Amy C. Justice
Background: People living with HIV frequently achieve long-term viral suppression necessitating better metrics of disease burden for clinical management and research. The Veterans Aging Cohort Study (VACS) Index predicts hospitalization, mortality, and other outcomes, using routinely available clinical data. We sought to enhance the index by evaluating whether nadir CD4, CD8, CD4/CD8 ratio, white blood count (WBC) or absolute neutrophil count (ANC), albumin, and body mass index (BMI) enhanced prediction. The original index categorized predictors for ease of understanding and calculation of a risk score. We also sought to expand categories and develop a continuous variable model, suitable for use with automated calculation, to provide higher resolution. Methods: VACS, includes all HIV infected patients in VA Care. Among those who initiated ART 1996–2013, (excluding any treated for HCV infection), we obtained laboratory values from a randomly selected visit 2000–2014, at least one year after ART initiation. Patients were followed for 5-year, all cause mortality until September 30, 2016. We fit Cox models starting with currently used predictors (age, CD4, HIV-1 RNA, hemoglobin, FIB4, eGFR and HCV status) and decided to include new variables based on model fit, chi-square, strength and significance of individual levels and c-statistic. Functional form for continuous variables was determined graphically. Adequacy of final models was assessed with Kaplan-Meier plots by deciles of risk. Results: Among 28,390 patients there were 7,293 deaths (7.2 per 100 person-years) in median 4.1 years of follow-up. Nadir CD4, CD8, CD4:CD8 did not improve prediction. WBC and ANC performed equally but WBC was more widely available. C-statistics improved from 0.776 for the original VACS Index (in this sample) to 0.805. Conclusion: Addition of WBC, albumin, and BM enhances utility of the VACS Index as a measure of overall severity of disease both as an outcome for research and for patient monitoring in the clinical setting. Validation in external cohorts is in progress.
by
Lesley S. Park;
Janet P. Tate;
Maria C. Rodriguez-Barradas;
David Rimland;
Matthew B. Goetz;
Cynthia Gibert;
Sheldon T. Brown;
Michael J. Kelley;
Amy C. Justice;
Robert Dubrow
Background: 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.
Methods: 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.
Results: 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.
Conclusions: 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.