Patterns of comorbidity among persons with human immunodeficiency virus (HIV) are not well described. We compared comorbidity among veterans with and without HIV infection. The sample consisted of 33,420 HIV-infected veterans and 66,840 HIV-uninfected veterans. We identified and clustered 11 comorbid conditions using validated International Classification of Diseases, 9th Revision, Clinical Modification codes. We defined multimorbidity as the presence of conditions in all clusters. Models restricted to HIV-infected veterans were adjusted for CD4 cell count and viral load. Comorbidity was common (prevalence, 60%-63%), and prevalence varied by HIV status. Differences remained when the veterans were stratified by age. In multivariable analyses, older HIV-infected veterans were more likely to have substance use disorder and multimorbidity. Renal, vascular, and pulmonary diseases were associated with CD4 cell count <200 cells/mm3; hypertension was associated with CD4 cell count >200 cells/mm3. Comorbidity is the rule, and multimorbidity is common among veterans with HIV infection. Patterns of comorbidity differ substantially by HIV status, age, and HIV severity. Primary care guidelines require adaptation for persons with HIV infection.
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Margaret T. May;
Jorg-Janne Vehreschild;
Adam Trickey;
Niels Obel;
Peter Reiss;
Fabrice Bonnet;
Murielle Mary-Krause;
Hasina Samji;
Matthias Cavassini;
Michael John Gill;
Leah C. Shepherd;
Heidi M. Crane;
Antonella d'Arminio Monforte;
Greer A. Burkholder;
Margaret M. Johnson;
Paz Sobrino-Vegas;
Pere Domingo;
Robert Zangerle;
Amy C. Justice;
Timothy R. Sterling;
Jose M. Miro;
Jonathan A.C. Sterne;
Jodie L. Guest
Background. CD4 count at start of combination antiretroviral therapy (ART) is strongly associated with short-term survival, but its association with longer-term survival is less well characterized. Methods. We estimated mortality rates (MRs) by time since start of ART (<0.5, 0.5-0.9, 1-2.9, 3-4.9, 5-9.9, and ≥10 years) among patients from 18 European and North American cohorts who started ART during 1996-2001. Piecewise exponential models stratified by cohort were used to estimate crude and adjusted (for sex, age, transmission risk, period of starting ART [1996-1997, 1998-1999, 2000-2001], and AIDS and human immunodeficiency virus type 1 RNA at baseline) mortality rate ratios (MRRs) by CD4 count at start of ART (0-49, 50-99, 100-199, 200-349, 350-499, ≥500 cells/μL) overall and separately according to time since start of ART. Results. A total of 6344 of 37 496 patients died during 359 219 years of follow-up. The MR per 1000 person-years was 32.8 (95% confidence interval [CI], 30.2-35.5) during the first 6 months, declining to 16.0 (95% CI, 15.4-16.8) during 5-9.9 years and 14.2 (95% CI, 13.3-15.1) after 10 years' duration of ART. During the first year of ART, there was a strong inverse association of CD4 count at start of ART with mortality. This diminished over the next 4 years. The adjusted MRR per CD4 group was 0.97 (95% CI,. 94-1.00; P =. 054) and 1.02 (95% CI,. 98-1.07; P =. 32) among patients followed for 5-9.9 and ≥10 years, respectively. Conclusions. After surviving 5 years of ART, the mortality of patients who started ART with low baseline CD4 count converged with mortality of patients with intermediate and high baseline CD4 counts.
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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.
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P. Todd Korthuis;
David A. Fiellin;
Kathleen A. McGinnis;
Melissa Skanderson;
Amy C. Justice;
Adam J. Gordon;
Donna Almario Doebler;
Steven M. Asch;
Lynn E. Fiellin;
Kendall Bryant;
Cynthia L. Gibert;
Stephen Crystal;
Matthew Bidwell Goetz;
David Rimland;
Maria C. Rodriguez-Barradas;
Kevin L. Kraemer
HIV-infected patients with substance use experience suboptimal health outcomes, possibly because of variations in care. OBJECTIVES: To assess the association between substance use and the quality of HIV care (QOC) received. RESEARCH DESIGN: Retrospective cohort study. SUBJECTS: HIV-infected patients enrolled in the Veterans Aging Cohort Study. MEASURES: We collected self-report substance use data and abstracted 9 HIV quality indicators (QIs) from medical records. Independent variables were unhealthy alcohol use (AUDIT-C score ≥4) and illicit drug use (self-report of stimulants, opioids, or injection drug use in past year). Main outcome was the percentage of QIs received, if eligible. We estimated associations between substance use and QOC using multivariable linear regression. RESULTS: The majority of the 3410 patients were male (97.4%) and black (67.0%) with a mean age of 49.1 years (SD = 8.8). Overall, 25.8% reported unhealthy alcohol use, 22% illicit drug use, and participants received 81.5% (SD = 18.9) of QIs. The mean percentage of QIs received was lower for those with unhealthy alcohol use versus not (59.3% vs. 70.0%, P < 0.001) and those using illicit drugs vs. not (57.8% vs. 70.7%, P < 0.001). In multivariable models, unhealthy alcohol use (adjusted β-2.74; 95% confidence interval:-4.23 to-1.25) and illicit drug use (adjusted β-3.51; 95% CI:-4.99 to-2.02) remained inversely associated with the percentage of QIs received. CONCLUSIONS: Although the overall QOC for these HIV-infected Veteran patients was high, gaps persist for those with unhealthy alcohol and illicit drug use. Interventions that address substance use in HIV-infected patients may improve the QOC received.
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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
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Christopher T. Rentsch;
Janet P. Tate;
Tessa Steel;
Adeel A. Butt;
Cynthia L. Gibert;
Laurence Huang;
Margaret Pisani;
Guy W. Soo Hoo;
Stephen Crystal;
Maria C. Rodriguez-Barradas;
Sheldon T. Brown;
Matthew S. Freiberg;
Christopher J. Graber;
Joon W. Kim;
David Rimland;
Amy C. Justice;
David A. Fiellin;
Kristina A. Crothers;
Kathleen M. Akgun
Background:HIV, hepatitis C virus (HCV), and alcohol-related diagnoses (ARD) independently contribute increased risk of all-cause hospitalization. We sought to determine annual medical intensive care unit (MICU) admission rates and relative risk of MICU admission between 1997 and 2014 among people with and without HIV, HCV, and ARD, using data from the largest HIV and HCV care provider in the United States.
Setting:Veterans Health Administration.
Methods:Annual MICU admission rates were calculated among 155,550 patients in the Veterans Aging Cohort Study by HIV, HCV, and ARD status. Adjusted rate ratios and 95% confidence intervals (CIs) were estimated with Poisson regression. Significance of trends in age-adjusted admission rates were tested with generalized linear regression. Models were stratified by calendar period to identify shifts in MICU admission risk over time.Results:Compared to HIV-/HCV-/ARD- patients, relative risk of MICU admission decreased among HIV-mono-infected patients from 61% (95% CI: 1.56 to 1.65) in 1997-2009% to 21% (95% CI: 1.16 to 1.27) in 2010-2014, increased among HCV-mono-infected patients from 22% (95% CI: 1.16 to 1.29) in 1997-2009% to 54% (95% CI: 1.43 to 1.67) in 2010-2014, and remained consistent among patients with ARD only at 46% (95% CI: 1.42 to 1.50). MICU admission rates decreased by 48% among HCV-uninfected patients (P-trend <0.0001) but did not change among HCV+ patients (P-trend = 0.34).
Conclusion:HCV infection and ARD remain key contributors to MICU admission risk. The impact of each of these conditions could be mitigated with combination of treatment of HIV, HCV, and interventions targeting unhealthy alcohol use.
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
We examined the effectiveness of integrated stepped alcohol treatment (ISAT) on alcohol use and HIV outcomes among patients living with HIV (PLWH) and alcohol use disorder (AUD).
Methods
In this multi-site randomized trial conducted in five Veterans Affairs-based HIV clinics , we enrolled PLWH and AUD who were not otherwise receiving formal alcohol treatment. Using a web-based clinical trial management system, participants were randomized in a 1:1 fashion to receive ISAT or treatment as usual (TAU). ISAT involved: Step 1 - Addiction Physician Management (APM), Step 2- APM plus Motivational Enhancement Therapy (MET), and Step 3 – Specialty referral. Participants were stepped up at weeks 4 and 12 if they exceeded a priori drinking criteria. Treatment as usual (TAU) involved referral. The primary outcome was drinks per week over the past 30 days at week 24 by Timeline Followback. The trial is registered at ClinicalTrials.gov, number NCT01410123.
Findings
Between January 28, 2013 and July 14, 2017, we randomized 128 participants to receive ISAT (n=63) and TAU (n=65). Fifty-two percent (30/57) ISAT participants advanced to Step 2 and 57% (17/30) to Step 3. Fifty one percent (32/63) in ISAT vs. 26% (17/65) in TAU received at least one alcohol medication (p=0·004). Both groups decreased alcohol consumption. At week 24 (primary outcome), we did not detect a difference between the ISAT and TAU groups in drinks per week (Least square mean (Lsmean) [SD]= 10·4 [16·5] vs. 15·6 [17·6]), adjusted mean difference [AMD] [95% CI]= −4·2 [−9·4, 0·9], p=0·11)
Interpretation
ISAT increases receipt of alcohol treatments without changes in drinking at week 24. Strategies to implement and enhance ISAT are needed.
by
Kaku A. So-Armah;
Joyce Chang;
Charles Alcorn;
Vincent Lo Re;
Jason V. Baker;
Russell Tracy;
Adeel A. Butt;
David Rimland;
Brian K. Agan;
Cynthia L. Gibert;
Matthew B. Goetz;
Krisann K. Oursler;
Maria C. Rodriguez-Barradas;
Lewis H. Kuller;
Sheldon T. Brown;
James H. Stein;
Melissa Skanderson;
Amy C. Justice;
Matthew S. Freiberg
Background: HIV is associated with end-organ diseases of aging via unclear mechanisms. Longitudinally assessing how HIV infection and ART initiation affect biomarkers of end organ function/disease could clarify these mechanisms. We investigated longitudinal changes in clinical biomarkers following 1) HIV infection and 2) ART initiation with evidence of viral suppression.
Methods: Cohort: Veterans Aging Cohort Study Virtual Cohort (VACS VC). VACS VC is a longitudinal cohort of HIV infected (HIV+) and race-ethnicity, sex, age, and clinical site-matched uninfected Veterans enrolled in the same calendar year. Inclusion criteria: a negative and successively positive (>six months) HIV antibody test. We used Wilcoxon signedrank tests to analyze 1) the effect of HIV infection on lipids, renal, hepatic and hematologic/cardiovascular biomarkers and 2)whether ART initiation with HIV-1 RNA<500 cpm reverts any changes back to pre-HIV levels
Results: 422 Veterans had at least 1 biomarker measurement available prior to HIV infection and prior to ART initiation. 297 had at least 1 biomarker measurement available prior to HIV infection and after ART initiation with evidence of viral suppression. Mean age prior to HIV infection was 43 years. HIV infection was associated with reduction in total cholesterol, HDL cholesterol, LDL cholesterol, serum albumin, ALT, platelet count, hemoglobin and elevation of FIB-4 score and triglycerides. These changes occurred without significant changes in BMI. ART initiation (with HIV-1 RNA<500cpm) did not reverse alteration in triglycerides, LDL cholesterol, hemoglobin, or FIB-4 to pre-HIV infection levels.
Conclusions: HIV infection is associated with longitudinal changes in serum levels of several biomarkers of end-organ function/disease and mortality. Multiple biomarkers (triglycerides, LDL cholesterol, hemoglobin, and FIB-4) remain altered from levels prior to HIV infection levels even following inititiation of ART and evidence of viral suppression. These results give insights into underlying mechanisms of increased risk for aging-related chronic diseases in the context of HIV infection.
by
Michael T. Yin;
Stephanie Shiau;
David Rimland;
Cynthia L. Gibert;
Roger J. Bedimo;
Maria C. Rodriguez-Barradas;
Katherine Harwood;
Josh Aschheim;
Amy C. Justice;
Julie A. Womack
Background: FRAX is a validated, computer-based clinical fracture risk calculator that estimates the 10-year risk of major osteoporotic (clinical spine, forearm, hip, or shoulder) fracture, and hip fracture alone. It is widely used for decision making in fracture prevention, but it may underestimate the risk in HIV-infected individuals. Some experts recommend considering HIV as a cause of secondary osteoporosis when calculating FRAX in HIV-infected individuals. Methods: From the Veterans Aging Cohort Study Virtual Cohort, we included 24,451 HIV-infected and uninfected men aged 50-70 years with complete data in the year 2000 to approximate all but 2 factors (ie, history of secondary osteoporosis and parental hip fracture) for modified-FRAX calculation without bone density and 10-year observational data for incident fragility fracture. The accuracy of the modified-FRAX calculation was compared by the observed/estimated (O/E) ratios of fracture by HIV status. Results: The accuracy of modified-FRAX was less for HIV-infected [O/E 1.62, 95% confidence interval (CI) 1.45 to 1.81] than uninfected men (O/E 1.29, 95% CI: 1.19 to 1.40), but improved when HIV was included as a cause of secondary osteoporosis (O/E 1.20, 95% CI: 1.08 to 1.34). However, only 3%-6% of men with incident fractures were correctly identified by the modified-FRAX using accepted FRAX thresholds for pharmacologic therapy. Conclusions: Modified-FRAX underestimated the fracture rates more in older HIV-infected than in otherwise similar uninfected men. The accuracy improved when HIV was included as a cause of secondary osteoporosis, but it still performed poorly for case finding. Further studies are necessary to determine how to use FRAX or define an HIV-specific index to risk stratify for screening and treatment in older HIV-infected individuals.
by
Debika Bhattacharya;
Chi-hong Tseng;
Janet P. Tate;
Vincent Lo Re;
Cynthia L. Gibert;
Adeel A. Butt;
Sheldon T. Brown;
Joseph K. Lim;
Maria C. Rodriguez-Barradas;
David Rimland;
Erica Kaufman;
Amy C. Justice;
Matthew Bidwell Goetz
HIV+/HCV+ persons with isolated HBcAb have a higher prevalence of advanced fibrosis than persons who are non-immune to HBV, who have resolved HBV, or who are HbsAb+ only.