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
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.
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.
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
Matthew S. Freiberg;
Ionut Bebu;
Russell Tracy;
Kaku So-Armah;
Jason Okulicz;
Anuradha Ganesan;
Adam Armstrong;
Thomas O'Bryan;
David Rimland;
Amy C. Justice;
Brian K. Agan;
Infectious Disease Clinical Research Program HIV Working Group
The mechanism underlying the excess risk of non-AIDS diseases among HIV infected people is unclear. HIV associated inflammation/hypercoagulability likely plays a role. While antiretroviral therapy (ART) may return this process to pre-HIV levels, this has not been directly demonstrated. We analyzed data/specimens on 249 HIV+ participants from the US Military HIV Natural History Study, a prospective, multicenter observational cohort of >5600 active duty military personnel and beneficiaries living with HIV. We used stored blood specimens to measure D-dimerand Interleukin-6 (IL-6) at three time points: pre-HIV seroconversion, ≥6 months post-HIV seroconversion but prior to ART initiation, and ≥6 months post-ART with documented HIV viral suppression on two successive evaluations. We evaluated the changes in biomarker levels between time points, and the association between these biomarker changes and future non-AIDS events. During a median follow-up of 3.7 years, there were 28 incident non-AIDS diseases. At ART initiation, the median CD4 count was 361 cells/mm3; median duration of documented HIV infection 392 days; median time on ART was 354 days. Adjusted mean percent increase in D-dimer levels from pre-seroconversion to post-ART was 75.1% (95% confidence interval 24.6-148.0, p = 0.002). This increase in D-dimer was associated with a significant 22% increase risk of future non-AIDS events (p = 0.03). Changes in IL-6 levels across time points were small and not associated with future non-AIDS events. In conclusion, ART initiation and HIV viral suppression does not eliminate HIV associated elevation in D-dimer levels. This residual pathology is associated with an increased risk of future non-AIDS diseases.
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
Vincent Lo Re III;
Micheal J. Kallan;
Janet P. Tate;
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 S. Park;
Robert Dubrow;
K. Rajender Reddy;
Jay R. Kostman;
Amy C. Justice;
A. Russell Localio
Background. End-stage liver disease (ESLD) is an important cause of morbidity among human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients. Quantifying the risk of this outcome over time could help determine which coinfected patients should be targeted for risk factor modification and HCV treatment. We evaluated demographic, clinical, and laboratory variables to predict risk of ESLD in HIV/HCV-coinfected patients receiving antiretroviral therapy (ART).
Methods. We conducted a retrospective cohort study among 6016 HIV/HCV-coinfected patients who received ART within the Veterans Health Administration between 1997 and 2010. The main outcome was incident ESLD, defined by hepatic decompensation, hepatocellular carcinoma, or liver-related death. Cox regression was used to develop prognostic models based on baseline demographic, clinical, and laboratory variables, including FIB-4 and aspartate aminotransferase-to-platelet ratio index, previously validated markers of hepatic fibrosis. Model performance was assessed by discrimination and decision curve analysis.
Results. Among 6016 HIV/HCV patients, 532 (8.8%) developed ESLD over a median of 6.6 years. A model comprising FIB-4 and race had modest discrimination for ESLD (c-statistic, 0.73) and higher net benefit than alternative strategies of treating no or all coinfected patients at relevant risk thresholds. For FIB-4 >3.25, ESLD risk ranged from 7.9% at 1 year to 26.0% at 5 years among non-blacks and from 2.4% at 1 year to 14.0% at 5 years among blacks.
Conclusions. Race and FIB-4 provided important predictive information on ESLD risk among HIV/HCV patients. Estimating risk of ESLD using these variables could help direct HCV treatment decisions among HIV/HCV-coinfected patients.
by
Oluwatosin A. Badejo;
Chung-Chou Chang;
Kaku A. So-Armah;
Russell P. Tracy;
Jason V. Baker;
David Rimland;
Adeel A. Butt;
Adam J. Gordon;
Charles R. Rinaldo;
Kevin Kraemer;
Jeffrey H. Samet;
Hilary A. Tindle;
Matthew B. Goetz;
Maria C. Rodriguez-Barradas;
Roger Bedimo;
Cynthia L. Gibert;
David A. Leaf;
Lewis H. Kuller;
Steven G. Deeks;
Amy C. Justice;
Matthew S. Freiberg
Human Immunodeficiency Virus- (HIV-) infected persons have a higher risk for acute myocardial infarction (AMI) than HIV-uninfected persons. Earlier studies suggest that HIV viral load, CD4+ T-cell count, and antiretroviral therapy are associated with cardiovascular disease (CVD) risk. Whether CD8+ T-cell count is associated with CVD risk is not clear. We investigated the association between CD8+ T-cell count and incident AMI in a cohort of 73,398 people (of which 97.3% were men) enrolled in the U.S. Veterans Aging Cohort Study-Virtual Cohort (VACS-VC). Compared to uninfected people, HIV-infected people with high baseline CD8+ T-cell counts (>1065 cells/mm3) had increased AMI risk (adjusted HR=1.82, P<0.001, 95% CI: 1.46 to 2.28). There was evidence that the effect of CD8+ T-cell tertiles on AMI risk differed by CD4+ T-cell level: compared to uninfected people, HIV-infected people with CD4+ T-cell counts ≥200 cells/mm3 had increased AMI risk with high CD8+ T-cell count, while those with CD4+ T-cell counts <200 cells/mm3 had increased AMI risk with low CD8+ T-cell count. CD8+ T-cell counts may add additional AMI risk stratification information beyond that provided by CD4+ T-cell counts alone.
by
Kirsha S. Gordon;
E. Jennifer Edelman;
Amy C. Justice;
David A. Fiellin;
KAthleen Akgun;
Stephen Crystal;
Mona Duggal;
Joseph L. Goulet;
David Rimland;
Kendall J. Bryant
Black and Hispanic (minority) MSM have a higher incidence of HIV than white MSM. Multiple sexual partners, being under the influence of drugs and/or alcohol during sex, having a detectable HIV-1 RNA, and non-condom use are factors associated with HIV transmission. Using data from the Veterans Aging Cohort Study, we consider minority status and sexual orientation jointly to characterize and compare these factors. White non-MSM had the lowest prevalence of these factors (p < 0.001) and were used as the comparator group in calculating odds ratios (OR). Both MSM groups were more likely to report multiple sex partners (white MSM OR 7.50; 95 % CI 5.26, 10.71; minority MSM OR 10.24; 95 % CI 7.44, 14.08), and more likely to be under the influence during sex (white MSM OR 2.15; 95 % CI 1.49, 3.11; minority MSM OR 2.94; 95 % CI 2.16, 4.01). Only minority MSM were more likely to have detectable HIV-1 RNA (OR 1.87; 95 % CI 1.12, 3.11). Both MSM groups were more likely to use condoms than white non-MSM. These analyses suggest that tailored interventions to prevent HIV transmission among minority MSM are needed, with awareness of the potential co-occurrence of risk factors.
by
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.