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
Ionut Bebu;
Janet Tate;
David Rimland;
Octavio Mesner;
Grace E. Macalino;
Anuradha Ganesan;
Jason F. Okulicz;
Mary Bavaro;
Amy C. Weintrob;
Amy C. Justice;
Brian K. Agan
Background: The Veterans Aging Cohort Study (VACS) index is a weighted combination of age and 8 clinical variables. It has been well correlated with all-cause mortality among HIV-infected patients. The US Military HIV Natural History Study (NHS) cohort provides a different validation population profile, being younger and healthier. A significant portion of the US HIV population is similarly composed; so, evaluation of the VACS index in this population is of great interest.
Methods: NHS subjects have medical history and laboratory data collected at 6-month visits. We performed an external validation of the VACS index in the NHS evaluating correlation, discrimination, and calibration for all-cause mortality after highly active antiretroviral therapy initiation (HI). We then tested whether combining longitudinal VACS index values at different time points improves prediction of mortality.
Results: The VACS index at 1 year after HI was well correlated with all-cause mortality (Harrell c statistic 0.78), provided good discrimination (log-rank P < 0.05), and was marginally well calibrated using Brier score. Accounting for VACS index at HI and 6 months after HI significantly improved a standard model, including only the VACS index at 1 year after HI (net reclassification improvement = 25.2%, 95% CI: 10.9% to 48.9%).
Conclusions: The VACS index was well correlated and provided good discrimination with respect to all-cause mortality among highly active antiretroviral therapy initiating subjects in the NHS. Moderate overprediction of mortality in this young, healthy population suggests minor recalibration that could improve fit among similar patients. Considering VACS index at HI and 6 months improved outcome prediction and allowed earlier risk assessment.
by
E. Jennifer Edelman;
Stephen A. Maisto;
Nathan B. Hansen;
Christopher J. Cutter;
James Dziura;
Yanhong Deng;
Lynn E. Fiellin;
Patrick G. O'Connor;
Roger Bedimo;
Cynthia L. Gibert;
Vincent Marconi;
David Rimland;
Maria C. Rodriguez-Barradas;
Michael S. Simberkoff;
Janet P. Tate;
Amy C. Justice;
Kendall J. Bryant;
David A. Fiellin
Background: At-risk levels of alcohol use threaten the health of patients with HIV (PWH), yet evidence-based strategies to decrease alcohol use and improve HIV-related outcomes in this population are lacking. We examined the effectiveness of integrated stepped alcohol treatment (ISAT) on alcohol use and HIV outcomes among PWH and at-risk alcohol use. Methods: In this multi-site, randomized trial conducted between January 28, 2013 through July 14, 2017, we enrolled PWH and at-risk alcohol use [defined as alcohol consumption of ≥ 14 drinks per week or ≥ 4 drinks per occasion in men ≤ 65 years old or ≥ 7 drinks per week or ≥ 3 drinks per occasion in women or men > 65 years old]. ISAT (n = 46) involved: Step 1- Brief Negotiated Interview with telephone booster, Step 2- Motivational Enhancement Therapy, and Step 3- Addiction Physician Management. Treatment as usual (TAU) (n = 47) involved receipt of a health handout plus routine care. Analyses were conducted based on intention to treat principles. Results: Despite a multi-pronged approach, we only recruited 37% of the target population (n = 93/254). Among ISAT participants, 50% advanced to Step 2, among whom 57% advanced to Step 3. Participants randomized to ISAT and TAU had no observed difference in drinks per week over the past 30 days at week 24 (primary outcome) [least square means (Ls mean) (95% CI) = 8.8 vs. 10.6; adjusted mean difference (AMD) (95% CI) = - 0.4 (- 3.9, 3.0)]. Conclusion: An insufficient number of patients were interested in participating in the trial. Efforts to enhance motivation of PWH with at-risk alcohol use to engage in alcohol-related research and build upon ISAT are needed. Trial registration Clinicaltrials.gov: NCT01410123, First posted August 4, 2011
by
Jessica R. White;
Chung-Chou H. Chang;
Kaku A. So-Armah;
Jesse C. Stewart;
Samir Kumar Gupta;
Adeel A. Butt;
Cynthia L. Gibert;
David Rimland;
Maria C. Rodriguez-Barradas;
David A. Leaf;
Roger J. Bedimo;
John S. Gottdiener;
Willem J. Kop;
Stephen S. Gottlieb;
Matthew J. Budoff;
Tasneem Khambaty;
Hilary Tindle;
Amy C. Justice;
Matthew S. Freiberg
Background: Both HIV and depression are associated with increased heart failure (HF) risk. Depression, a common comorbidity, may further increase the risk of HF among HIV+ adults. We assessed the association between HIV, depression and incident HF.
Methods and Results: Veterans Aging Cohort Study (VACS) participants free from cardiovascular disease at baseline (N = 81,427; 26,908 HIV+, 54,519 HIV-) were categorized into four groups: HIV- without major depressive disorder (MDD) [reference]; HIV- with MDD; HIV+ without MDD; and HIV+ with MDD. ICD-9 codes from medical records were used to determine MDD and the primary outcome, HF. After 5.8 follow-up years, HF rates per 1000 person-years were highest among HIV+ participants with MDD (9.32; 95% CI, 8.20–10.6). In Cox proportional hazards models, HIV+ participants with MDD had significantly higher risk of HF [adjusted hazard ratio (aHR) = 1.68; 95% CI, 1.45–1.95] compared to HIV- participants without MDD. MDD was associated with HF in separate fully adjusted models for HIV- and HIV+ participants (aHR = 1.21; 1.06–1.37 and 1.29; 1.11–1.51, respectively). Among those with MDD, baseline antidepressant use was associated with lower risk of incident HF events (aHR = 0.76; 0.58–0.99).
Conclusions: Our study is the first to suggest MDD is an independent risk factor for HF in HIV+ adults. These results reinforce the importance of identifying and managing MDD among HIV+ patients. Future studies must clarify mechanisms linking HIV, MDD, antidepressants, and HF; and identify interventions to reduce HF morbidity and mortality in those with both HIV and MDD.
by
Vincent Lo Re;
Michael J. Kallan;
Janet P. Tate;
A. Russell Localio;
Joseph K. Lim;
Matthew Bidwell Goetz;
Marina B. Klein;
David Rimland;
Maria C. Rodriguez-Barradas;
Adeel A. Butt;
Cynthia L. Gibert;
Sheldon T. Brown;
Lesley Park;
Robert Dubrow;
K. Rajender Reddy;
Jay R. Kostman;
Brian L. Strom;
Amy C. Justice
Background: The incidence and determinants of hepatic decompensation have been incompletely examined among patients coinfected 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.
Objective: 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.
Design: Retrospective cohort study. Setting: Veterans Health Administration. Patients: 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.
Measurements: Incident hepatic decompensation, determined by diagnoses of ascites, spontaneous bacterial peritonitis, or esophageal variceal hemorrhage.
Results: 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. Limitation: Observational study of predominantly male patients.
Conclusion: Despite receiving ART, patients co-infected with HIV and HCV had higher rates of hepatic decompensation than HCVmonoinfected patients. Rates of decompensation were higher for co-infected patients with advanced liver fibrosis, severe anemia, diabetes, and nonblack race. Primary Funding Source: National Institutes of Health.
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.
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
Christopher T. Rentsch;
Emily Cartwright;
Neel Gandhi;
Sheldon T. Brown;
Maria C. Rodriguez-Barradas;
Matthew Bidwell Goetz;
Vincent Marconi;
Cynthia L. Gibert;
Vincent Lo Re, III;
David A. Fiellin;
Amy C. Justice;
Janet P. Tate
Purpose: Pharmacoepidemiologic studies using electronic health record data could serve an important role in assessing safety and effectiveness of direct-acting antiviral therapy for chronic hepatitis C virus (HCV) infection, but the validity of these data needs to be determined. We evaluated the accuracy of pharmacy fill records in the national Veterans Health Administration (VA) Corporate Data Warehouse (CDW) as compared to facility-level electronic health record. Methods: Patients prescribed a direct-acting antiviral regimen at five VA sites between 2014 and 2016 were randomly selected and reviewed. A random sample of patients with chronic HCV infection without evidence of HCV treatment during the study period also underwent chart review. We calculated positive predictive value and negative predictive value overall and by site. Results: Of the 501 patients who received a total of 2416 prescriptions, 494 were validated using data extracted from CDW 6 months after the study period, yielding a positive predictive value of 98.6% (95% confidence interval, 97.6%–99.6%). Of the 100 patients with chronic HCV infection without prescriptions for HCV treatment, 99 were confirmed not to have received antiviral treatment (negative predictive value, 99.0%; 95% confidence interval, 97.1%–100%). Conclusions: These findings provide assurance to researchers who use national VA CDW data for retrospective cohort studies that the CDW contains accurate information on HCV therapies in the modern treatment era.
by
Andrew Boulle;
Michael Schomaker;
Margaret T. May;
Robert S. Hogg;
Bryan E. Shepherd;
Susana Monge;
Olivia Keiser;
Fiona C. Lampe;
Janet Giddy;
James Ndirangu;
Daniela Garone;
Matthew Fox;
Suzanne M. Ingle;
Peter Reiss;
Francois Dabis;
Dominique Costagliola;
Antonella Castagna;
Kathrin Ehren;
Colin Campbell;
M. John Gill;
Michael Saag;
Amy C. Justice;
Jodie L. Guest;
Heidi M. Crane;
Matthias Egger;
Jonathan A. C. Sterne
After accounting for under-ascertainment of mortality, with increasing duration on ART, the mortality rate on HIV treatment in South Africa declines to levels comparable to or below those described in participating North American cohorts, while substantially narrowing the differential with the European cohorts.Please see later in the article for the Editors' Summary.High early mortality in patients with HIV-1 starting antiretroviral therapy (ART) in sub-Saharan Africa, compared to Europe and North America, is well documented. Longer-term comparisons between settings have been limited by poor ascertainment of mortality in high burden African settings. This study aimed to compare mortality up to four years on ART between South Africa, Europe, and North America.Data from four South African cohorts in which patients lost to follow-up (LTF) could be linked to the national population register to determine vital status were combined with data from Europe and North America. Cumulative mortality, crude and adjusted (for characteristics at ART initiation) mortality rate ratios (relative to South Africa), and predicted mortality rates were described by region at 0–3, 3–6, 6–12, 12–24, and 24–48 months on ART for the period 2001–2010. Of the adults included (30,467 [South Africa], 29,727 [Europe], and 7,160 [North America]), 20,306 (67%), 9,961 (34%), and 824 (12%) were women. Patients began treatment with markedly more advanced disease in South Africa (median CD4 count 102, 213, and 172 cells/µl in South Africa, Europe, and North America, respectively). High early mortality after starting ART in South Africa occurred mainly in patients starting ART with CD4 count <50 cells/µl. Cumulative mortality at 4 years was 16.6%, 4.7%, and 15.3% in South Africa, Europe, and North America, respectively. Mortality was initially much lower in Europe and North America than South Africa, but the differences were reduced or reversed (North America) at longer durations on ART (adjusted rate ratios 0.46, 95% CI 0.37–0.58, and 1.62, 95% CI 1.27–2.05 between 24 and 48 months on ART comparing Europe and North America to South Africa). While bias due to under-ascertainment of mortality was minimised through death registry linkage, residual bias could still be present due to differing approaches to and frequency of linkage.
by
Jeanette M. Tetrault;
Janet P. Tate;
E. Jennifer Edelman;
Adam J. Gordon;
Vincent Lo Re;
Joseph K. Lim;
David Rimland;
Joseph Goulet;
Stephen Crystal;
Julie R. Gaither;
Cynthia L. Gibert;
Maria C. Rodriguez-Barradas;
Lynn E. Fiellin;
Kendall Bryant;
Amy C. Justice;
David A. Fiellin
Introduction: Individuals with HIV and hepatitis C (HCV) infection, alcohol use disorder, or who are prescribed potentially hepatotoxic medications may be at increased risk for buprenorphine (BUP) associated hepatotoxicity. Materials and methods: We examined a cohort of HIV-infected and uninfected patients receiving an initial BUP prescription between 2003 and 2012. We compared changes in alanine and aspartate aminotransferases (ALT and AST) and total bilirubin (TB) stratified by HIV status. We identified cases of liver enzyme elevation (LEE), TB elevation (TBE), and conducted chart review to assess for cases of drug induced liver injury (DILI) and death. We examined associations between age, sex, race, HIV-infection, HCV-infection, alcohol use disorder, and prescription of other potentially heptatotoxic medications with the composite endpoint of LEE, TBE, and DILI. Results: Of 666 patients prescribed BUP, 36% were HIV-infected, 98% were male, 60% had RNA-confirmed HCV infection, 50% had a recent diagnosis of alcohol use disorder, and 64% were prescribed other potentially hepatotoxic medications. No clinically significant changes were observed in median ALT, AST and TB and these changes did not differ between HIV-infected and uninfected patients. Compared with uninfected patients, HIV-infected (OR 7.3, 95% CI 2.1–26.1, p = 0.002), HCV-infected (OR 4.9 95% CI 1.6–15.2, p = 0.007) or HIV/HCV co-infected patients (OR 6.9, 95%CI 2.1–22.2, p = 0.001) were more likely to have the composite endpoint of LEE, TB elevation or DILI, in analyses that excluded 60 patients with evidence of pre-existing liver injury. 31 patients had LEE, 14/187 HIV-infected and 17/340 uninfected (p = 0.25); 11 had TBE, including 9/186 HIV-infected and 2/329 uninfected (p = 0.002); 8 experienced DILI, 4/202 HIV-infected and 4/204 uninfected (p = 0.45). There were no significant associations with alcohol use disorder or prescription of other potentially hepatotoxic medications after adjustment for HIV/HCV status. Conclusions: Liver enzymes and TB are rarely elevated in HIV-infected and uninfected patients receiving BUP. Risk of hepatotoxicity was greater in individuals infected with HIV, HCV, or HIV/HCV co-infection, who may benefit from increased monitoring.