Judith I. Tsui

Association of Opioid Agonist Therapy With Lower Incidence of Hepatitis C Virus Infection in Young Adult Injection Drug Users

IMPORTANCE Injection drug use is the primary mode of transmission for hepatitis C virus (HCV) infection. Prior studies suggest opioid agonist therapy may reduce the incidence of HCV infection among injection drug users; however, little is known about the effects of this therapy in younger users. OBJECTIVE To evaluate whether opioid agonist therapy was associated with a lower incidence of HCV infection in a cohort of young adult injection drug users. DESIGN, SETTING, AND PARTICIPANTS Observational cohort study conducted from January 3, 2000, through August 21, 2013, with quarterly interviews and blood sampling. We recruited young adult (younger than 30 years) injection drug users who were negative for anti-HCV antibody and/or HCV RNA. EXPOSURES Substance use treatment within the past 3 months, including non-opioid agonist forms of treatment, opioid agonist (methadone hydrochloride or buprenorphine hydrochloride) detoxification or maintenance therapy, or no treatment. MAIN OUTCOMES AND MEASURES Incident HCV infection documented with a new positive result for HCV RNA and/or HCV antibodies. Cumulative incidence rates (95% CI) of HCV infection were calculated assuming a Poisson distribution. Cox proportional hazards regression models were fit adjusting for age, sex, race, years of injection drug use, homelessness, and incarceration. RESULTS Baseline characteristics of the sample (n = 552) included median age of 23 (interquartile range, 20-26) years; 31.9% female; 73.1% white; 39.7% who did not graduate from high school; and 69.2% who were homeless. During the observation period of 680 person-years, 171 incident cases of HCV infection occurred (incidence rate, 25.1 [95% CI, 21.6-29.2] per 100 person-years). The rate ratio was significantly lower for participants who reported recent maintenance opioid agonist therapy (0.31 [95% CI, 0.14-0.65]; P = .001) but not for those who reported recent non-opioid agonist forms of treatment (0.63 [95% CI, 0.37-1.08]; P = .09) or opioid agonist detoxification (1.45 [95% CI, 0.80-2.69]; P = .23). After adjustment for other covariates, maintenance opioid agonist therapy was associated with lower relative hazards for acquiring HCV infection over time (adjusted hazard ratio, 0.39 [95% CI, 0.18-0.87]; P = .02). CONCLUSIONS AND RELEVANCE In this cohort of young adult injection drug users, recent maintenance opioid agonist therapy was associated with a lower incidence of HCV infection. Maintenance treatment with methadone or buprenorphine for opioid use disorders may be an important strategy to prevent the spread of HCV infection among young injection drug users.

Relationship between Hepatitis C and Chronic Kidney Disease: Results from the Third National Health and Nutrition Examination Survey

Previous research supports an association between hepatitis C virus (HCV) infection and glomerulonephritis. However, little is known about the association between HCV and chronic kidney disease. The cross-sectional association between prevalent hepatitis C seropositivity and albuminuria and estimated GFR (eGFR), respectively, was examined among 15,029 participants in the Third National Health and Nutrition Examination Survey (NHANES III). In the multivariate analysis, we noted an age-dependent association between HCV seropositivity and albuminuria (adjusted odds ratios and 95% confidence intervals 0.83, 0.39 to 1.75 for ages 20 to 39; 1.84, 1.00 to 3.37 for ages 40 to 59; 2.47, 1.27 to 4.80 for > or =60 yr of age). There was no significant association observed for hepatitis C seropositivity and low eGFR (<60 ml/min per 1.73 m(2); adjusted odds ratios and 95% confidence interval for all ages 0.89, 0.49 to 1.62). Among a representative sample of the US population, hepatitis C is independently associated with albuminuria among adults over the age of 40; however, it does not seem to be significantly associated with a low eGFR in this population-based cross-sectional analysis.

Buprenorphine Treatment for Hospitalized, Opioid-Dependent Patients: A Randomized Clinical Trial

IMPORTANCE Buprenorphine opioid agonist treatment (OAT) has established efficacy for treating opioid dependency among persons seeking addiction treatment. However, effectiveness for out-of-treatment, hospitalized patients is not known. OBJECTIVE To determine whether buprenorphine administration during medical hospitalization and linkage to office-based buprenorphine OAT after discharge increase entry into office-based OAT, increase sustained engagement in OAT, and decrease illicit opioid use at 6 months after hospitalization. DESIGN, SETTING, AND PARTICIPANTS From August 1, 2009, through October 31, 2012, a total of 663 hospitalized, opioid-dependent patients in a general medical hospital were identified. Of these, 369 did not meet eligibility criteria. A total of 145 eligible patients consented to participation in the randomized clinical trial. Of these, 139 completed the baseline interview and were assigned to the detoxification (n = 67) or linkage (n = 72) group. INTERVENTIONS Five-day buprenorphine detoxification protocol or buprenorphine induction, intrahospital dose stabilization, and postdischarge transition to maintenance buprenorphine OAT affiliated with the hospitals primary care clinic (linkage). MAIN OUTCOMES AND MEASURES Entry and sustained engagement with buprenorphine OAT at 1, 3, and 6 months (medical record verified) and prior 30-day use of illicit opioids (self-report). RESULTS During follow-up, linkage participants were more likely to enter buprenorphine OAT than those in the detoxification group (52 [72.2%] vs 8 [11.9%], P < .001). At 6 months, 12 linkage participants (16.7%) and 2 detoxification participants (3.0%) were receiving buprenorphine OAT (P = .007). Compared with those in the detoxification group, participants randomized to the linkage group reported less illicit opioid use in the 30 days before the 6-month interview (incidence rate ratio, 0.60; 95% CI, 0.46-0.73; P < .01) in an intent-to-treat analysis. CONCLUSIONS AND RELEVANCE Compared with an inpatient detoxification protocol, initiation of and linkage to buprenorphine treatment is an effective means for engaging medically hospitalized patients who are not seeking addiction treatment and reduces illicit opioid use 6 months after hospitalization. However, maintaining engagement in treatment remains a challenge. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00987961.

Association of Hepatitis C Virus Seropositivity With Inflammatory Markers and Heart Failure in Persons With Coronary Heart Disease: Data From the Heart and Soul Study

BACKGROUND How hepatitis C virus (HCV) affects coronary heart disease (CHD) risk factors and outcomes is largely unknown. METHODS AND RESULTS Among a cohort of patients with stable CHD, we examined the association between HCV seropositivity and levels of inflammatory markers (C-reactive protein [CRP], fibrinogen, interleukin-6, and tumor necrosis factor [TNF]-alpha) and risk for the following outcomes: death, cardiovascular (CV) events, and heart failure events. A total of 84 (8.6%) participants were found to be seropositive for HCV. HCV-seropositive patients were found to have significantly lower adjusted mean levels of CRP (2.6 vs. 4.4; P < .01) and fibrinogen (340 vs. 398; P < .01), but higher levels of TNF-alpha (7.1 vs. 4.8; P < .01). Age-adjusted rates for HCV seropositive vs. seronegative were as follows: death 93 vs. 42/1,000p-y (P < .01), CV events 62 vs. 40 (P=.13), and heart failure 76 vs. 29 (P < .01). After adjustment for demographic and clinical factors, HCV remained significantly associated with an increased risk for heart failure events (HR=2.13; 95% CI: 1.19-3.80). CONCLUSIONS In this cohort with CHD, HCV seropositive participants had higher rates of death, CV events, and heart failure hospitalizations during follow-up. After adjustment for CV risk factors, HCV seropositivity remained independently associated with risk for heart failure events.

Prevalence and Long-Term Effects of Occult Hepatitis B Virus Infection in HIV-Infected Women

Occult hepatitis B virus (HBV) infection is of concern in human immunodeficiency virus (HIV)-infected persons. We observed that 2% of 400 HIV-infected women with antibodies to hepatitis B core antigen alone had occult HBV infection (i.e., detectable HBV DNA in the absence of HBV surface antigen). CD4 cell counts of <200 cells/mm3 were more common among occult HBV-infected women than among those without occult HBV infection. Aminotransferase levels did not appear to be associated with being positive for HBV DNA.

Hepatitis C Seropositivity and Kidney Function Decline Among Women With HIV: Data From the Women's Interagency HIV Study

BACKGROUND How coinfection with hepatitis C virus (HCV) impacts on the trajectory of kidney function in human immunodeficiency virus (HIV)-infected patients is unclear. This study examined the effect of HCV infection on kidney function over time in women infected with HIV. STUDY DESIGN Retrospective observational cohort. SETTING & PARTICIPANTS Study sample included participants from the Womens Interagency HIV Study who were HIV infected and had undergone HCV antibody testing and serum creatinine measurement at baseline. PREDICTOR HCV seropositivity. OUTCOMES & MEASUREMENT Estimated glomerular filtration rate (eGFR) calculated from semi-annual serum creatinine measurements using the 4-variable Modification of Diet in Renal Diseases (MDRD) Study equation. Linear mixed models were used to evaluate the independent effect of HCV seropositivity on eGFR over time, adjusting for demographic factors, comorbid conditions, illicit drug use, measures of HIV disease status, use of medications, and interactions with baseline low eGFR (<60 mL/min/1.73 m(2)). RESULTS Of 2,684 HIV-infected women, 952 (35%) were found to be HCV seropositive. In 180 women with chronic kidney disease (CKD) at baseline (eGFR < 60 mL/min/1.73 m(2)), HCV seropositivity was independently associated with a fully adjusted net decrease in eGFR of approximately 5% per year (95% confidence interval, 3.2 to 7.2) relative to women who were seronegative. In contrast, HCV infection was not independently associated with a decrease in eGFR in women without low eGFR at baseline (P < 0.001 for interaction). LIMITATIONS The MDRD Study equation has not been validated as a measure of GFR in persons with HIV or HCV infection. Proteinuria was not included in the study analysis. Because the study is observational, effects of residual confounding cannot be excluded. CONCLUSIONS In HIV-infected women with CKD, coinfection with HCV is associated with a modest, but statistically significant, decrease in eGFR over time. More careful monitoring of kidney function may be warranted for HIV-infected patients with CKD who are also coinfected with HCV.

Awareness of Hepatitis C Diagnosis is Associated with Less Alcohol Use Among Persons Co-Infected with HIV

BACKGROUND AND OBJECTIVEIt is unknown whether testing HIV-infected individuals for hepatitis C virus (HCV) and informing them of their HCV status impacts subsequent alcohol use. We hypothesized that HIV-infected individuals with current or past alcohol problems who reported being told they had HCV were more likely to 1) abstain from alcohol and 2) not drink unhealthy amounts compared to individuals who had not been told.DESIGN, PARTICIPANTS, AND MEASUREMENTSData from a prospective, observational cohort study (HIV-Longitudinal Interrelationships of Viruses and Ethanol) were used to assess the association between awareness of having HCV at baseline and subsequent abstinence and not drinking unhealthy amounts as reported at 6-month follow-up intervals. General estimating equations logistic regression was used to account for the correlation from using repeated observations from the same subject over time. We adjusted for age, sex, race, homelessness, injection drug use, depressive symptoms, and having abnormal liver tests.RESULTSParticipants who reported being told they had HCV were more likely to report abstaining from alcohol (AOR = 1.60; 95% CI: 1.13 to 2.27) and not drinking unhealthy amounts (AOR = 1.46; 95% CI: 1.01 to 2.11).CONCLUSIONSAmong patients infected with HIV who had a history of alcohol problems, reporting being told one had HCV was associated with greater abstinence from alcohol and less unhealthy amounts of drinking.

The Impact of Chronic Hepatitis C on Health-Related Quality of Life in Homeless and Marginally Housed Individuals with HIV

Although infection with Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV) frequently co-exist, there has been little research to determine the effects of HIV/HCV co-infection on health-related quality of life (HRQOL). We performed a cross-sectional analysis of baseline data from 216 participants enrolled in a community based study of HIV-infected homeless and marginally housed individuals, using multivariable linear regression analysis to determine if co-infection with HCV was independently associated with lower short-form 36 (SF-36) questionnaire scores. We found that individuals with HCV had significantly lower mean SF-36 scores in the domains of physical functioning, bodily pain, social functioning and role limitation due to emotional health, and that HIV/HCV co-infection was independently associated with a lower physical component score but not a lower mental component score after controlling for numerous covariates. These results suggest that co-infection with HCV may have an adverse effect on HRQOL among homeless and marginally housed individuals with HIV.

Risk behaviors after hepatitis C virus seroconversion in young injection drug users in San Francisco.

BACKGROUND The rationale for screening populations at risk for hepatitis C virus infection (HCV) includes the possibility of altering risk behaviors that impact disease progression and transmission. This study prospectively examined young injection drug users (IDU) to determine if behaviors changed after they were made aware of HCV seroconversion. METHODS We estimated the effects of HCV seroconversion coupled with post-test counseling on risk behaviors (alcohol use, non-injection and injection drug use, lending and sharing injecting equipment, and having sex without a condom) and depression symptoms using conditional logistic regression, fitting odds-ratios for immediately after disclosure and 6 and 12 months later, and adjusting for secular effects. RESULTS 112 participants met inclusion criteria, i.e. they were documented HCV seronegative at study onset and subsequently seroconverted during the follow-up period, with infection confirmed by HCV RNA testing. HCV seroconversion was independently associated with a decreased likelihood of consuming alcohol (OR=0.52; 95% CI: 0.27-1.00, p=0.05) and using non-injection drugs (OR=0.40; 95% CI: 0.20-0.81, p=0.01) immediately after disclosure, however, results were not sustained over time. There were significant (p<0.05) declines in the use of alcohol, injection and non-injection drugs, and sharing equipment associated with time that were independent from the effect of seroconversion. CONCLUSIONS Making young IDU aware of their HCV seroconversion may have a modest effect on alcohol and non-injection drug use that is not sustained over time.

Inflammatory cytokines and mortality in a cohort of HIV-infected adults with alcohol problems.

Background:HIV infection leads to chronic inflammation and alterations in levels of inflammatory cytokines. The association between cytokine levels and mortality in HIV infection is not fully understood. Methods:We analyzed data from a cohort of HIV-infected adults with alcohol problems who were recruited in 2001–2003, and were prospectively followed until 2010 for mortality using the National Death Index. The main independent variables were inflammatory biomarkers [interleukin-6 (IL-6), IL-10, tumor necrosis factor-&agr;, C-reactive protein, serum amyloid A, monocyte chemotactic protein-1, and cystatin-C], measured at baseline in peripheral blood and categorized as high (defined as being in the highest quartile) vs. low. A secondary analysis was conducted using inflammatory burden score, defined as the number of biomarkers in the highest quartile (0, 1, 2 or ≥3). Cox models were used to assess the association between both biomarker levels and inflammatory burden with mortality adjusting for potential confounders. Results:Four hundred HIV-infected patients were included (74.8% men, mean age 42 years, 50% hepatitis C virus-infected). As of 31 December 2009, 85 patients had died. In individual multivariable analyses for each biomarker, high levels of IL-6 and C-reactive protein were significantly associated with mortality [hazard ratio = 2.49 (1.69–5.12), P <0.01] and [hazard ratio = 1.87 (1.11–3.15), P = 0.02], respectively. There was also a significant association between inflammatory burden score and mortality [hazard ratio = 2.18 (1.29–3.66) for ≥3 vs. 0, P = 0.04]. In the fully adjusted multivariable analysis, high levels of IL-6 remained independently associated with mortality [hazard ratio = 2.57 (1.58–4.82), P <0.01]. Conclusion:High IL-6 levels and inflammatory burden score were associated with mortality in a cohort of HIV-infected adults with alcohol problems.