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1.  Managing Hepatitis C in Users of Illicit Drugs 
Current hepatitis reports  2007;6(2):60-67.
Persons who inject illicit drugs are the group most severely affected by the hepatitis C epidemic but the least likely to receive treatment. Controlling the epidemic will require developing strategies for effectively treating drug users. A growing number of reports have shown that a substantial proportion of drug users treated for hepatitis C can achieve sustained virologic responses even if they have psychiatric comorbidity and even if they continue to use drugs while receiving hepatitis C treatment. Successfully treating hepatitis C in injection drug users requires collaboration between those with expertise in hepatitis and those with expertise in caring for substance users. Careful attention to management of adverse effects and strong links with mental health services are important. Further research is needed to better define which patients can be successfully treated and the program elements that are critical for success. In the meantime, substantial progress can be made using current knowledge if appropriate resources are brought to bear.
PMCID: PMC3690289  PMID: 23801897
2.  A variant upstream of IFNL3 (IL28B) creating a novel interferon gene IFNL4 is associated with impaired clearance of hepatitis C virus 
Nature genetics  2013;45(2):164-171.
Chronic infection with hepatitis C virus (HCV) is a common cause of liver cirrhosis and cancer. We performed RNA-sequencing in primary human hepatocytes activated with synthetic dsRNA to mimic HCV infection. Upstream of IFNL3 (IL28B) on chromosome 19q13.13, we discovered a novel, transiently induced region that harbors dinucleotide variant ss469415590 (TT/ΔG), which is in high linkage disequilibrium with rs12979860, a genetic marker strongly associated with HCV clearance. ss469415590-ΔG is a frame-shift variant that creates a novel primate-specific gene, designated interferon lambda 4 (IFNL4), which encodes a protein of moderate similarity with IFNL3. Compared to rs12979860, ss469415590 is more strongly associated with HCV clearance in individuals of African ancestry, whereas it provides comparable information in Europeans and Asians. Transient over-expression of IFNL4 in a hepatoma cell line induced STAT1/STAT2 phosphorylation and expression of interferon-stimulated genes. Our findings provide new insights into the genetic regulation of HCV clearance and its clinical management.
PMCID: PMC3793390  PMID: 23291588
3.  Prevention and Treatment of Hepatitis C in Injection Drug Users 
Hepatology (Baltimore, Md.)  2002;36(5 Suppl 1):S210-S219.
Injection drug users constitute the largest group of persons infected with the hepatitis C virus (HCV) in the United States, and most new infections occur in drug users. Controlling hepatitis C in the U.S. population, therefore, will require developing, testing, and implementing effective prevention and treatment strategies for persons who inject drugs. Fortunately, a substantial body of research and clinical experience exists on the prevention and management of chronic viral diseases among injection drug users. The need to implement interventions to stop the spread of HCV among drug users is critical. The capacity of substance-use treatment programs need to be expanded to accommodate all who want and need treatment. Physicians and pharmacists should be educated in how to provide access to sterile syringes and to teach safe injection techniques, both of which are lifesaving interventions. The treatment of hepatitis C in drug users requires an interdisciplinary approach that brings together expertise in treating hepatitis and caring for drug users. Treatment decisions should be made individually by patients with their physicians, based on a balanced assessment of risks and benefits and the patient's personal values. Physicians should carefully assess, monitor, and support adherence and mental health in all patients, regardless of whether drug use is known or suspected. Research is needed to better understand how best to prevent and treat hepatitis C in substance users. In the meantime, substantial progress can be made if existing knowledge and resources are brought to bear.
PMCID: PMC1629041  PMID: 12407596
5.  Infrequent Reinfection after Successful Treatment for Hepatitis C Virus Infection in Injection Drug Users 
We followed-up 18 injection drug users for a mean of 33.8 months (range, 4–55 months) after successful treatment for hepatitis C virus (HCV) infection. Fifteen (83%) of the patients remained HCV RNA–negative, 1 patient was not tested, and 2 patients had test results positive for HCV RNA. The estimated rate of reinfection as a result of injection drug use was 0–4.1 cases per 100 person-years (cumulative incidence, 0%–12.6% at 48 months after completion of treatment). Of 50 patients originally treated, 15 (30%) were HCV RNA–negative 3 years later.
PMCID: PMC1510898  PMID: 15546094
7.  Genome wide association study of spontaneous resolution of hepatitis C virus infection 
Annals of internal medicine  2013;158(4):235-245.
Hepatitis C virus (HCV) infections occur worldwide and either spontaneously resolve or persist and markedly increase the person’s lifetime risk of cirrhosis and hepatocellular carcinoma. Although HCV persistence occurs more often in persons of African ancestry and in persons with a genetic variant near IL28B, the genetic basis is not well understood.
To evaluate the host genetic basis for spontaneous resolution of HCV infection.
Two-stage genome wide association study (GWAS).
13 international multicenter study sites.
919 individuals with serum HCV antibodies but no HCV RNA (spontaneous resolution) and 1482 individuals with serum HCV antibodies and RNA (persistence).
Frequencies of 792,721 SNPs.
Differences in allele frequencies between persons with spontaneous resolution and persistence were identified on chromosomes 19q13.13 and 6p21.32. On chromosome 19, allele frequency differences localized near IL28B and included rs12979860 (overall per-allele OR = 0.45, P = 2.17 × 10−30) and 10 additional SNPs spanning 55,000 bases. On chromosome 6, allele frequency differences localized near genes for class II human leukocyte antigens (HLA) and included rs4273729 (overall per-allele OR= 0.59, P = 1.71 × 10−16) near DQB1*03:01 and an additional 116 SNPs spanning 1,090,000 base pairs. The associations in chromosomes 19 and 6 were independent, additive, and explain an estimated 14.9% (95% CI: 8.5–22.6%) of the variation in HCV resolution in those of European-Ancestry, and 15.8% (95% CI:4.4–31.0%) in individuals of African-Ancestry. Replication of the chromosome 6 SNP, rs4272729 in an additional 746 individuals confirmed the findings (p=0.015).
Epigenetic effects were not studied.
IL28B and HLA class II are independently associated with spontaneous resolution of HCV infection and SNPs marking IL28B and DQB1*03:01 may explain ~15% of spontaneous resolution of HCV infection.
PMCID: PMC3638215  PMID: 23420232
8.  HCV RNA Levels in a Multi-Ethnic Cohort of Injection Drug Users: Human Genetic, Viral and Demographic Associations 
Hepatology (Baltimore, Md.)  2012;56(1):86-94.
In patients with chronic hepatitis C, the hepatitis C virus (HCV) RNA level is an important predictor of treatment response. To explore the relationship of HCV RNA with viral and demographic factors, as well as IL28B genotype, we examined viral levels in an ethnically diverse group of injection drug users (IDUs). Between 1998 and 2000, the Urban Health Study (UHS) recruited IDUs from street settings in San Francisco Bay area neighborhoods. Participants who were positive by HCV EIA were tested for HCV viremia by a bDNA assay. HCV genotype was determined by sequencing the HCV NS5B region. For a subset of participants, IL28B rs12979860 genotype was determined by Taqman. Among 1701 participants with HCV viremia, median age was 46 years and median duration of injection drug use was 26 years; 56.0% were African American and 34.0% were of European ancestry (non-Hispanic). HIV-1 prevalence was 13.9%. The overall median HCV RNA level was 6.45 log10 copies/ml. In unadjusted analyses, higher levels were found with older age, male gender, African American ancestry, HBV infection, HIV-1 infection and IL28B rs12979860-CC genotype; compared to participants infected with HCV genotype 1, HCV RNA was lower in participants with genotype 3 or genotype 4. In an adjusted analysis, age, gender, racial ancestry, HIV-1 infection, HCV genotype and IL28B rs12979860 genotype were all independently associated with HCV RNA. Conclusion: The level of HCV viremia is influenced by a large number of demographic, viral and human genetic factors.
PMCID: PMC3369001  PMID: 22331649
epidemiology; genetics; HCV; IL28B; viremia
10.  Racial/Ethnic Differences in Spontaneous HCV Clearance in HIV Infected and Uninfected Women 
Digestive diseases and sciences  2012;58(5):1341-1348.
Among individuals without human immunodeficiency virus (HIV), African Americans have lower spontaneous clearance of hepatitis C virus (HCV) than Caucasians, and women have higher clearance than men. Few studies report racial/ethnic differences in acute HCV in HIV infected, or Hispanic women. We examined racial/ethnic differences in spontaneous HCV clearance in a population of HCV mono- and co-infected women.
We conducted a cross sectional study of HCV seropositive women (897 HIV infected and 168 HIV uninfected) followed in the US multicenter, NIH-funded Women's Interagency HIV Study (WIHS), to determine the association of race/ethnicity with spontaneous HCV clearance, as defined by undetectable HCV RNA at study entry.
Among HIV and HCV seropositive women, 18.7 % were HCV RNA negative, 60.9 % were African American, 19.3 % Hispanic and 17.7 % Caucasian. HIV infected African American women were less likely to spontaneously clear HCV than Hispanic (OR 0.59, 95 % CI 0.38–0.93, p = 0.022) or Caucasian women (OR 0.57, 95 % CI 0.36–0.93, p = 0.023). Among HIV uninfected women, African Americans had less HCV clearance than Hispanics (OR 0.18, 95 % CI 0.07–0.48, p = 0.001) or Caucasians (OR 0.26, 95 % CI 0.09–0.79, p = 0.017). There were no significant differences in HCV clearance between Hispanics and Caucasians, among either HIV infected (OR 0.97, 95 % CI 0.57–1.66, p = 0.91) or uninfected (OR 1.45, 95 % CI 0.56–3.8, p = 0.45) women.
African Americans were less likely to spontaneously clear HCV than Hispanics or Caucasians, regardless of HIV status. No significant differences in spontaneous HCV clearance were observed between Caucasian and Hispanic women. Future studies incorporating IL28B genotype may further explain these observed racial/ethnic differences in spontaneous HCV clearance.
PMCID: PMC3663918  PMID: 23179159
African American; Hispanic; Acute hepatitis C; Female
11.  Spontaneous Clearance of Chronic Hepatitis C Virus Infection Is Associated With Appearance of Neutralizing Antibodies and Reversal of T-Cell Exhaustion 
The Journal of Infectious Diseases  2012;205(5):763-771.
Background. Hepatitis C virus (HCV) readily establishes chronic infection with exhaustion of HCV-specific T cells and escape from neutralizing antibodies. Spontaneous recovery from chronic infection is rare and has never to our knowledge been studied immunologically.
Methods. We prospectively studied, from prior to infection through >2 years of follow-up, cytokines, HCV-specific T cells, and antibodies, as well as viral sequence evolution in a white male who spontaneously cleared HCV genotype 1a after 65 weeks.
Results. Significant alanine aminotransferase and plasma cytokine elevation and broad HCV-specific T-cell responses did not result in HCV clearance in the acute phase. Frequency and effector function of HCV-specific T cells decreased thereafter, and HCV titers stabilized as is typical for the chronic phase. HCV clearance after 65 weeks followed the appearance of neutralizing antibodies at week 48 and was associated with reversal of HCV-specific T-cell exhaustion, as evidenced by reduced programmed death–1 (PD-1) expression and improved T-cell function. Clearance occurred without inflammation or superinfection with hepatitis B virus, human cytomegalovirus virus, influenza, and Epstein-Barr virus.
Conclusions. T-cell exhaustion is reversible at least in the first 2 years of chronic HCV infection, and this reversion in conjunction with neutralizing antibodies may clear HCV. These findings are relevant for immunotherapy of chronic infections.
PMCID: PMC3274373  PMID: 22293431
12.  IL28B rs12979860 Genotype and Spontaneous Clearance of Hepatitis C Virus in a Multi-Ethnic Cohort of Injection Drug Users: Evidence for a Supra-Additive Association 
The Journal of Infectious Diseases  2011;204(12):1843-1847.
Among 1369 Urban Health Study participants, we evaluated genetic models for the association of IL28B genotype (rs12979860 and rs8099917) with hepatitis C virus (HCV) clearance. For rs12979860, adjusted odds ratios for spontaneous HCV clearance were as follows: IL28B-CC, 3.88 (P < .001); IL28B-CT, 1.48 (P = .08). On the basis of Akaike information criteria values and χ2 tests, a supra-additive (quadratic) model fit these data best. Models based on rs8099917 provided poorer fit. Evidence that a supra-additive rs12979860-based model best fits the association of IL28B-genotype with HCV clearance may improve clinical prediction models and foster a better understanding of functional mechanisms underlying this association.
PMCID: PMC3209810  PMID: 22013224
13.  Induction of CXCR3- and CCR5-associated Chemokines during Acute Hepatitis C Virus Infection 
Journal of hepatology  2011;55(3):545-553.
Background and Aims
Characterization of inflammatory mediators, such as chemokines, during acute hepatitis C virus (HCV) infection might shed some light on viral clearance mechanisms.
Plasma levels of CXCR3 (CXCL9-11)- and CCR5 (CCL3-4)-associated chemokines, ALT and HCV RNA were measured in nine injection drug users (median 26 samples/patient) before and during ten acute (eight primary and two secondary) HCV infections. Using functional data analysis, we estimated smooth long-term trends in chemokine expression levels to obtain the magnitude and timing of over-all changes. Residuals were analyzed to characterize short-term fluctuations.
CXCL9-11 induction began 38–53 days and peaked 72–83 days after virus acquisition. Increases in ALT levels followed a similar pattern. Substantial negative autocorrelations of chemokine levels at one week lags suggested substantial week-to-week oscillations. Significant correlations were observed between CXCL10 and HCV RNA as well as ALT and CXCR3-associated chemokines measured in the preceding week, CCL3-4 expression levels did not change appreciably during acute HCV infection.
Elevation of CXCR3-associated chemokines late during acute HCV infection suggests a role for cellular immune responses in chemokine induction. Week-to-week oscillations of HCV RNA, chemokines, and ALT suggest frequent, repeated cycles of gain and loss of immune control during acute hepatitis C.
PMCID: PMC3094733  PMID: 21256906
CXCL9; CXCL10; CXCL11; CCL3; CCL4; inflammation
14.  Genetic Variation in CLDN1 and Susceptibility to Hepatitis C Virus Infection 
Journal of viral hepatitis  2009;17(3):192-200.
Claudin-1 is a recently discovered co-receptor for hepatitis C virus (HCV) that is required for late-stage binding of the virus. Because variants in the gene that encodes claudin-1 (CLDN1) could play a role in HCV infection, we conducted a ‘whole gene association study’ among injection drug users (IDUs) to examine whether CLDN1 genetic variants were associated with the risk of HCV infection or with viral clearance. In a cross sectional study, we examined genotype results for 50 single nucleotide polymorphisms (SNPs) across the CLDN1 gene region, comparing genotypes among participants with chronic HCV (n=658) to those in IDUs who had cleared HCV (n=199) or remained HCV-uninfected (n=68). Analyses were controlled for racial ancestry (African American or European American) by stratification and logistic regression modeling. We found that participants who remained uninfected more often carried CLDN1 promoter region SNPs -15312C [odds ratio (OR), 1.72; 95% confidence interval (CI) 1.00-2.94; p=0.048], -7153A (OR, 2.13; 95% CI, 1.25-3.62; p=0.006) and -5414C (OR, 1.78; 95% CI, 1.06-3.00; p=0.03). HCV-uninfected participants less often carried CLDN1 IVS1-2983C (OR, 0.55; 95% CI, 0.31-0.97; p=0.04), which lies in intron 1. CLDN1 -15312C, -7153A and -5414C formed a haplotype in both the African American and European American participants and a haplotype analysis supported the association of CLDN1 -7153A in the HCV-uninfected participants. The analyses of HCV clearance revealed no associations with any SNP. These results indicate that genetic variants in regulatory regions of CLDN1 may alter susceptibility to HCV infection.
PMCID: PMC2921226  PMID: 19674288
claudin-1; epidemiology; genetic; susceptibility; viral receptor
15.  HCV-Specific T-Cell Immune Responses in Seronegative Injection Drug Users 
Journal of viral hepatitis  2008;16(1):10-20.
T-cell responses to HCV antigens have been reported in high-risk HCV seronegative persons, suggesting that an effective cellular immune response might be able to clear infection without the development of antibodies. Such findings, however, could be explained by waning antibody or cross-reactivity to other antigens. To address these issues, we assessed T-cell responses in high-risk, seronegative, young IDUs to multiple peptide mixes spanning the entire HCV genome.
We evaluated HCV-specific T-cell responses in 26 young (age 18-33 years) aviremic, seronegative IDUs (median duration of injection, 6 years) by interferon-γ ELISpot assay using 429 overlapping HCV peptides pooled in 21 mixes. Seventeen aviremic, seropositive IDUs (spontaneous resolvers) and 15 healthy people were used as positive and negative controls, respectively.
The percentage of patients with HCV-specific cellular immune responses was similar in seronegative and seropositive aviremic IDUs (46% versus 59%, p=0.4), while these responses were not detected in any of the negative controls. Among the seronegative IDUs, 6 (23%) had intermediate to very strong responses to 10-20 peptide mixes and another 6 (23%) had moderately strong responses to 2 to 6 mixes. The 12 seronegative IDUs with HCV-specific T-cell responses had higher demographic and behavioral risk profiles than the 14 IDUs without T-cell responses (estimated risk of HCV infection, 0.47 vs. 0.26, p <0.01).
HCV-specific T-cell responses are common among high-risk, seronegative IDUs. The responses are broad and are associated with risk factors for HCV exposure, suggesting that they reflect true exposure to HCV in seronegative persons.
PMCID: PMC2997348  PMID: 18647233
16.  Hepatitis C Patients' Self-reported Adherence to Pegylated Interferon and Ribavirin 
Prior research on adherence to Hepatitis C treatment has documented rates of dose reductions and early treatment discontinuation, but little is known about patients' dose-taking adherence.
To assess the prevalence of missed doses of pegylated interferon and ribavirin and examine the correlates of dose-taking adherence in clinic settings.
180 patients on treatment for Hepatitis C (23% co-infected with HIV) completed a cross-sectional survey at the site of their Hepatitis C care.
Seven percent of patients reported missing at least one injection of pegylated interferon in the last four weeks and 21% reported missing at least one dose of ribavirin in the last 7 days. Dose-taking adherence was not associated with HCV viral load.
Self-reported dose nonadherence to Hepatitis C treatment occurs frequently. Further studies of dose nonadherence (assessed by method other than self-report) and its relationship to HCV virologic outcome are warranted.
PMCID: PMC2891196  PMID: 19086329
Adherence; HCV; HIV; co-infection; interferon; ribavirin
17.  Naturally occurring dominant resistance mutations to HCV protease and polymerase inhibitors in treatment-naïve patients 
Hepatology (Baltimore, Md.)  2008;48(6):1769-1778.
Resistance mutations to HCV NS3 protease inhibitors in <1% of the viral quasispecies may still allow >1000-fold viral load reductions upon treatment, consistent with their reported reduced replicative fitness in vitro. Recently, however, an R155K protease mutation was reported as the dominant quasispecies in a treatment-naïve individual, raising concerns about possible full drug resistance. To investigate the prevalence of dominant STAT-C resistance mutations in the population we analyzed HCV genome sequences from 507 treatment-naïve HCV genotype 1 infected patients from the US, Germany and Switzerland. Phylogenetic sequence analysis and viral load data were used to identify the possible spread of replication competent, drug resistant viral strains in the population and to infer the consequences of these mutations upon viral replication in vivo. Mutations described to confer resistance to the protease inhibitors Telaprevir, BILN2061, ITMN-191, SCH6 and Boceprevir, the NS5B polymerase inhibitor AG-021541, and to the NS4A antagonist ACH-806 were observed mostly as sporadic, unrelated cases, at frequencies between 0.3% and 2.8% in the population, including two patients with possible multi-drug resistance. Collectively, however, 8.6% of the genotype 1a and 1.4% of the genotype 1b infected patients carried at least one dominant resistance mutation. Viral loads were high in the majority of these patients, suggesting that drug resistant viral strains might achieve replication levels comparable to non-resistant viruses in vivo.
Conclusion: Naturally occurring dominant STAT-C resistance mutations are common in HCV genotype 1 infected treatment-naïve patients. Their influence on treatment outcome should further be characterized to evaluate possible benefits of drug resistance testing for individual tailoring of drug combinations when treatment options are limited due to previous non-response to peginterferon and ribavirin.
PMCID: PMC2645896  PMID: 19026009
NS3 protease inhibitor; NS5B polymerase inhibitor; Telaprevir; Boceprevir
18.  Hepatitis C Virus (HCV)–Specific Immune Responses of Long-Term Injection Drug Users Frequently Exposed to HCV 
The Journal of infectious diseases  2008;198(2):203-212.
Injection drug users (IDUs) who successfully clear hepatitis C virus (HCV) have a reduced risk of developing chronic reinfection, despite their continuing exposure to the virus. To identify immunological correlates for this apparent protection, we studied HCV-specific immune responses in long-term IDUs (duration, >10 years).
HCV-specific T cell responses were assessed in proliferation, enzyme-linked immunospot (ELISPOT), interferon (IFN)–γ secretion, and cytotoxicity assays, whereas HCV-specific antibodies were assessed in enzyme immunoassays (EIAs), chemiluminescent assays, and in vitro neutralization assays.
HCV-specific T cell proliferation and IFN-γ production were more common in nonviremic EIA-positive IDUs (16 [94%] of 17 IDUs) than in viremic EIA-positive IDUs (9 [45%] of 20 IDUs) (P = .003). They were also noted in 16 (62%) of 26 nonviremic EIA-negative IDUs. In contrast, 19 (90%) of 21 viremic IDUs displayed neutralizing antibodies (nAbs), compared with 9 (56%) of 16 nonviremic EIA-positive IDUs (P = .04) and 0 of 24 nonviremic EIA-negative IDUs. Nonviremic IDUs with nAbs were older (P = .0115) than those without nAbs, but these groups did not differ in terms of either injection drug use duration or HCV-specific T cell responses.
The reduced risk of HCV persistence in IDUs previously recovered from HCV infection correlated with T cell responses, and prolonged antigenic stimulation appears to be required to maintain humoral responses.
PMCID: PMC2699613  PMID: 18505381
19.  Naloxone Distribution and Cardiopulmonary Resuscitation Training for Injection Drug Users to Prevent Heroin Overdose Death: A Pilot Intervention Study 
Fatal heroin overdose has become a leading cause of death among injection drug users (IDUs). Several recent feasibility studies have concluded that naloxone distribution programs for heroin injectors should be implemented to decrease heroin overdose deaths, but there have been no prospective trials of such programs in North America. This pilot study was undertaken to investigate the safety and feasibility of training injection drug using partners to perform cardiopulmonary resuscitation (CPR) and administer naloxone in the event of heroin overdose. During May and June 2001, 24 IDUs (12 pairs of injection partners) were recruited from street settings in San Francisco. Participants took part in 8-hour training in heroin overdose prevention, CPR, and the use of naloxone. Following the intervention, participants were prospectively followed for 6 months to determine the number and outcomes of witnessed heroin overdoses, outcomes of participant interventions, and changes in participants’ knowledge of overdose and drug use behavior. Study participants witnessed 20 heroin overdose events during 6 months follow-up. They performed CPR in 16 (80%) events, administered naloxone in 15 (75%) and did one or the other in 19 (95%). All overdose victims survived. Knowledge about heroin overdose management increased, whereas heroin use decreased. IDUs can be trained to respond to heroin overdose emergencies by performing CPR and administering naloxone. Future research is needed to evaluate the effectiveness of this peer intervention to prevent fatal heroin overdose.
PMCID: PMC2570543  PMID: 15872192
Heroin; Heroin-related deaths; Injection drug use; Overdose; Prevention
20.  Community Characteristics Associated with HIV Risk among Injection Drug Users in the San Francisco Bay Area: A Multilevel Analysis 
Community characteristics have been associated with racial and ethnic health disparities for a wide range of ailments and conditions. Previous research has found that rates of AIDS cases among injection drug users (IDUs) vary by community characteristics. However, few studies have examined whether community characteristics are associated with HIV risk behaviors among IDUs. To address this gap in the literature, we examined the associations between census-tract-level community characteristics and injection-related and sex-related HIV risk behaviors among IDUs in the San Francisco Bay Area. Individual HIV risk behaviors were collected from 4,956 IDUs between 1998 and 2002. Using 2000 US census data, we constructed four census-level community measures: percent African American, percent male unemployment, percent of households that receive public assistance, and median household income. All community variables were measured continuously. Multilevel modeling was used to determine if community characteristics were associated with recent (in the last 6 months) receptive and distributive syringe sharing, multiple sex partners, and unprotected sex risk while controlling for potential individual-level confounders. In bivariate analysis, most of the census-tract-level community characteristics were significantly associated with injection-related HIV risk, while no community characteristics were associated with sex-related risk. However, results from multivariate multilevel models indicate that only percent African American in a census tract was associated with receptive [adjusted odds ratio (AOR) = 0.93; 95% confidence interval (CI) = 0.89, 0.99] and distributive syringe sharing (AOR = 0.94; 95% CI = 0.92, 0.99), net of individual-level characteristics. Accounting for individual-level factors in the multivariate model in the sex-related risk models revealed a significant inverse relationship between percent African American and propensity to engage in unprotected sex (AOR = 0.95; 95% CI = 0.92, 0.99); community-level characteristics remained unassociated with multiple sex partners. In this exploratory analysis, percent African American in a census tract was inversely associated with injection-related risk. The census-tract-level community characteristics we examined seem to exert little influence on individual risk among long-term chronic IDUs. More research is needed examining the influence of other community characteristics that were unmeasured in this paper but might be related to sex and drug risk among IDUs such as shooting galleries, crack houses, drug markets, and availability of preventive HIV services.
PMCID: PMC1988782  PMID: 17657607
Census data; Drug use; HIV/AIDS; Neighborhood; Risk factors
21.  Testing Strategy To Identify Cases of Acute Hepatitis C Virus (HCV) Infection and To Project HCV Incidence Rates▿  
Journal of Clinical Microbiology  2007;46(2):499-506.
Surveillance for hepatitis C virus (HCV) is limited by the challenge of differentiating between acute and chronic infections. In this study, we evaluate a cross-sectional testing strategy that identifies individuals with acute HCV infection and we estimate HCV incidence. Anti-HCV-negative persons from four populations with various risks, i.e., blood donors, Veterans Administration (VA) patients, young injection drug users (IDU), and older IDU, were screened for HCV RNA by minipool or individual sample nucleic acid testing (NAT). The number of detected viremic seronegative infections was combined with the duration of the preseroconversion NAT-positive window period (derived from analysis of frequent serial samples from plasma donors followed from NAT detection to seroconversion) to estimate annual HCV incidence rates. Projected incidence rates were compared to observed incidence rates. Projected HCV incidence rates per 100 person-years were 0.0042 (95% confidence interval [95% CI], 0.0025 to 0.007) for blood donors, 0.86 (95% CI, 0.02 to 0.71) for VA patients, 39.8 (95% CI, 25.9 to 53.7) for young IDU, and 53.7 (95% CI, 23.4 to 108.8) for older IDU. Projected rates were most similar to observed incidence rates for young IDU (33.4; 95% CI, 28.0 to 39.9). This study demonstrates the value of applying a cross-sectional screening strategy to detect acute HCV infections and to estimate HCV incidence.
PMCID: PMC2238141  PMID: 18032621
22.  MBL2 and Hepatitis C Virus Infection among Injection Drug Users 
Genetic variations in MBL2 that reduce circulating levels and alter functional properties of the mannose binding lectin (MBL) have been associated with many autoimmune and infectious diseases. We examined whether MBL2 variants influence the outcome of hepatitis C virus (HCV) infection.
Participants were enrolled in the Urban Health Study of San Francisco Bay area injection drug users (IDU) during 1998 through 2000. Study subjects who had a positive test for HCV antibody were eligible for the current study. Participants who were positive for HCV RNA were frequency matched to those who were negative for HCV RNA on the basis of ethnicity and duration of IDU. Genotyping was performed for 15 single nucleotide polymorphisms in MBL2. Statistical analyses of European American and African American participants were conducted separately.
The analysis included 198 study subjects who were positive for HCV antibody, but negative for HCV RNA, and 654 IDUs who were positive for both antibody and virus. There was no significant association between any of the genetic variants that cause MBL deficiency and the presence of HCV RNA. Unexpectedly, the MBL2 -289X promoter genotype, which causes MBL deficiency, was over-represented among European Americans who were HCV RNA negative (OR = 1.65, 95% CI 1.05–2.58), although not among the African Americans.
This study found no association between genetic variants that cause MBL deficiency and the presence of HCV RNA. The observation that MBL2 -289X was associated with the absence of HCV RNA in European Americans requires validation.
PMCID: PMC2413243  PMID: 18452612
Syringe exchange programs (SEPs) have been shown to be highly effective in reducing HIV transmission among injection drug users (IDUs). Despite this evidence, SEPs have not been implemented in many communities experiencing HIV epidemics among IDUs. We interviewed 17 key informants in nine U.S. cities to identify factors and conditions that facilitated or deterred the adoption of SEPs. Cities were selected to represent diversity in size, geographic location, AIDS incidence rates, and SEP implementation. Key informants included HIV prevention providers, political leaders, community activists, substance use and AIDS researchers, and health department directors. SEPs were established by one or more of three types of implementation models: (a) broad community coalition support, (b) community activist initiative, and (c) top-down decision making by government authorities. In each model, coalition building and community consultation were critical steps for the acceptance and sustainability of SEPs. When others were not prepared to act, community activists spearheaded SEP development, taking risks in the face of opposition, but often lacked the resources to sustain their efforts. Leadership from politicians and public health officials provided needed authority, clout, and access to resources. Researchers and scientific findings lent force and legitimacy to the effort. Rather than adopting adversarial positions, successful SEP implementers worked with or avoided the opposition. Fear of repercussions and lack of leadership were the greatest barriers to implementing SEPs. Communities that successfully implemented SEPs were those with activists willing to push the agenda, public officials willing to exercise leadership, researchers able to present authoritative findings, and proponents who effectively mobilized resources and worked to build community coalitions, using persistent but nonadversarial advocacy.
PMCID: PMC1510902  PMID: 15843111
24.  Written in Response to Scott LD: Treating Hepatitis C in Active Injection Drug Users 
PMCID: PMC1510900  PMID: 16128962
25.  Overcoming Barriers to Prevention, Care, and Treatment of Hepatitis C in Illicit Drug Users 
Injection drug use accounts for most of the incident infections with hepatitis C virus (HCV) in the United States and other developed countries. HCV infection is a complex and challenging medical condition in injection drug users (IDUs). Elements of care for hepatitis C in illicit drug users include prevention counseling and education; screening for transmission risk behavior; testing for HCV and human immunodeficiency virus infection; vaccination against hepatitis A and B viruses; evaluation for comorbidities; coordination of substance-abuse treatment services, psychiatric care, and social support; evaluation of liver disease; and interferon-based treatment for HCV infection. Caring for patients who use illicit drugs presents challenges to the health-care team that require patience, experience, and an understanding of the dynamics of substance use and addiction. Nonetheless, programs are successfully integrating hepatitis C care for IDUs into health-care settings, including primary care, methadone treatment and other substance-abuse treatment programs, infectious disease clinics, and clinics in correctional facilities.
PMCID: PMC1510897  PMID: 15768335

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