Hepatitis C virus reinfection in injection drug users

Spontaneous clearance of hepatitis C (HCV) may provide protection against reinfection. In a large community-based cohort study of 3,553 inner-city residents (mainly injection drug users), we identified HCV-infected individuals in whom virological clearance had occurred and compared the rate of reinfection in this group with that observed in previously uninfected members of the same cohort. We identified 926 HCV-uninfected and 658 HCV-infected viremic subjects at baseline, with 152 of 658 (23.1%) spontaneously clearing viremia over a median follow-up of 5.2 years (IQR, 2.8-7.4). At baseline, individuals with HCV clearance were more likely to be HIV coinfected (P < .001) and to be engaged in frequent illicit drug use (P = .004) and injection drug use (P < .001). The occurrence of HCV infection was lower in individuals with previous infection (14/152, 9.2%) compared with that in those without previous infection (172/926, 18.6%), with incidence rates of 1.8 (95% CI, 0.9-3.0 cases/100 person-years) and 8.1 (95% CI, 6.9-9.4 cases/100 person-years) cases/100 person-years, respectively, after accounting for follow-up. In a logistic regression analysis, with previous HCV infection assessed as a covariate with other potential confounding variables (age, sex, ethnicity, HIV infection, housing status, and illicit and injection drug use), individuals with previous HCV infection and viral clearance were 4 times less likely to develop infection than those infected for the first time (adjusted odds ratio, 0.23; 95% CI, 0.10-0.51, P < .001). In conclusion, individuals with clearance of HCV infection may have a lower risk of acquiring HCV than individuals who have never been infected, despite ongoing exposure to HCV.     

Attitudes toward needle-sharing and HIV transmission risk behavior among HIV+ injection drug users in clinical care

Risky behavior related to injection drug use accounts for a considerable proportion of incident HIV infection in the United States. Large numbers of injection drug users (IDUs) currently receive antiretroviral therapy in clinical settings and are accessible for risk-reduction interventions to reduce transmission of drug-resistant HIV and spread of HIV to uninfected others. The current study examined attitudes toward needle- or equipment-sharing among 123 HIV-positive IDUs in clinical care in an effort to understand the dynamics of such behavior and to create a basis for clinic-based risk-reduction interventions. Results indicate that at baseline, participants who reported extremely negative attitudes toward needle-sharing were less likely to have shared during the past month than those with less-extreme negative attitudes. Demographic, behavioral, and attitudinal variables were entered into a logistic regression model to examine needle-sharing group membership among HIV-positive IDUs. Being female and having less-extreme negative attitudes toward sharing were independent and significant correlates of sharing behavior. Interventions targeting needle-sharing attitudes deployed within the clinical care setting may be well-positioned to reduce HIV transmission among HIV-positive IDUs.     

Hepatitis C in injection drug users:It is time to treat

Injection drug users(IDUs)are at risk of hepatitis C virus(HCV)infection,due to needle and syringe sharing.Chronic HCV infection is a major cause of liver-related morbidity and mortality but can be cured with antiviral treatment leading to sustained viral response(SVR).It is well demonstrated that,when close cooperation between specialists in drug addiction and psychiatrists is assured,patients on maintenance treatment with methadone/buprenorphine can be treated for HCV with response rate,tolerability and side effects similar to those reported in non-IDUs.Current guidelines recommend that active injection drug use should not exclude patients from HCV treatment,but many services remain reluctant to treat IDUs.No significant pharmacodynamic interactions were reported between approved direct anti-viral agents(DAAs)and buprenorphine or methadone.Dose adjustments are not recommended;therefore DAAs appear to be theperfecttherapy for patients taking opiate substitutive therapy.These suggestions have been recently recognized by the European Association for the Study of the Liver(EASL)and included in EASL Recommendations on Treatment of Hepatitis C 2016.Guidelines confirm that HCV treatment for IDUs should be considered on an individualized basis and delivered within a multidisciplinary team setting;a history of intravenous drug use and recent drug use at treatment initiation are not associated with reduced SVR and decisions to treat must be made on a case-by-case basis.     

Hepatitis C virus-specific T-cell immune responses in seronegative injection drug users

Summary.  T-cell responses to hepatits C virus (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 evaluated HCV-specific T-cell responses in 26 young (age 18–33 years) aviremic, seronegative injection drug users (IDUs) (median duration of injection, 6 years) by interferon-γ enzyme-linked immunospot (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% vs 59%, P  = 0.4), while these responses were not detected in any of the negative controls. Among the seronegative IDUs, six (23%) had intermediate to very strong responses to 10–20 peptide mixes and another six (23%) had moderately strong responses for two to six mixes. The 12 seronegative IDUs with HCV-specific T-cell responses had higher demographical and behavioural risk profiles than the 14 IDUs without T-cell responses (estimated risk of HCV infection, 0.47 vs 0.26, P  < 0.01). In conclusion, 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.     

Hepatitis C virus seroconversion among young injection drug users: relationships and risks

The present study examined reasons for the high incidence of hepatitis C virus (HCV) infection among young injection drug users (IDUs). IDUs <30 years old who tested negative for HCV antibody were enrolled in a prospective cohort. Risk factors for seroconversion were examined using time-dependent regression analyses: 48 of 195 IDUs seroconverted to HCV, for an incidence rate of 25.1/100 person-years (95% confidence interval, 18.7-32.9/100 person-years). Independent risk factors included sharing needles with an HCV-infected sex partner (borderline statistical significance, P=.11) or a person who was not a sex partner, sharing nonsterile drug-preparation equipment, pooling money with another IDU to buy drugs, and exchanging sex for money. Ubiquitous behaviors among young IDUs, such as the forming of injecting or sexual partnerships and consequent sharing of needles and drug preparation equipment, are risk factors for HCV. Interventions to reduce HCV transmission must recognize the importance of relationships on injecting risk.     

Risk factors for methadone outside treatment programs: implications for HIV treatment among injection drug users

BACKGROUND: Diversion of methadone outside treatment programs occurs, yet reasons for use of 'street methadone' are characterized poorly. Self-medication for withdrawal symptoms is one plausible hypothesis. Among HIV-infected drug users, some antiretroviral medications can reduce potency of methadone, yet any association between such effects and the use of supplemental methadone sources remains undetermined. OBJECTIVE: To estimate the frequency and risk factors for use of street methadone. METHODS: Injection drug users (IDUs) recruited through extensive community outreach in 1988-89 and 1994 were followed semi-annually with questionnaires about health history, use of licit and illicit drugs including methadone and HIV-related assays. Analyses were performed using generalized estimating equation logistic regression. RESULTS: Of 2811 IDUs enrolled and eligible for analysis, 493 people reported use of street methadone over 12 316 person-years of follow-up (4.0/100 person-years). In multivariate analyses, street methadone use was more common among women, whites, those 40-59 years old, those who reported withdrawal symptoms, past methadone program attendance (6-12 months before visit), recent heroin injection with or without cocaine (but not cocaine alone), smoking or sniffing heroin and reported trading sex. Street methadone was not associated with HIV infection or treatment. CONCLUSION: The results suggest that older IDUs still using heroin may be using street methadone to treat signs of withdrawal. The absence of a higher rate of street methadone use in HIV seropositive IDUs reveals that antiretroviral/methadone interactions are not a primary determinant of use outside of treatment settings.     

Bone and joint infections in injection drug users

Skeletal infections in injection drug users have an insidious onset, present with indolent symptoms, and often occur in unusual locations. Unless physicians are familiar with the disease entities unique to the injection drug user, the diagnosis is frequently delayed. Systemic signs of infection are often lacking. The organisms causing the infection represent a wide spectrum; hence, empiric therapy is not generally recommended. Plain-film radiographs are of little help for early diagnosis. Imaging studies, especially radionucleotide studies and CT or MR imaging scans, can help localize the site of infection. For etiologic diagnosis of these infections, bone biopsy or needle aspiration of the involved bone or joint is required. The choice of antibiotic agent should be based on culture results and the antimicrobial susceptibility of the causative organism. Treatment may also involve surgical drainage or débridement of affected structures. Failure to manage acute bone and joint infection aggressively inevitably leads to chronic, often incurable, infection. Successful therapy requires a team approach including the internist and consultants from orthopedic surgery, infectious diseases, and substance abuse counselors.     

Hepatitis C virus infection in Italian intravenous drug users: epidemiological and clinical aspects

Abstract: The epidemological and clinical features of hepatitis C virus infection have been evaluated in a cohort of 227 intravenous drug users enrolled at a drug dependence treatment center in the Veneto area in 1992–1993 and followed periodically. Hepatitis C virus infection was detected using second-generation anti-HCV ELISA in 171 (75%) subjects at enrollment. Anti-HCV seropositivity correlated with: a) the duration of drug abuse: 91% of intravenous drug users injecting for more than 8 years were seropositive as compared to 40% of those with a history of abuse lasting 4 years or less, p<0.001; b) sharing of injection equipment: 85% anti-HCV positive intravenous drug users had shared at some time as compared to 64% seronegative subjects, p<0.001; c) seropositivity for immunodeficiency virus infection: 25% anti-HCV positive intravenous drug users were coinfected as compared to 3.5% anti-HCV negative, p<0.001; d) markers of ongoing (two cases) or previous hepatitis B virus infection were detected in 62% of anti-HCV positive but in 21% of anti-HCV negative cases, p<0.01. Two initially anti-HCV negative intravenous drug users seroconverted during follow up giving an incidence rate of hepatitis C virus infection of 6.2 per 100 person-years. During the survey abnormal alanine aminotransferase levels were detected in 75% anti-HCV positive but in 24% anti-HCV negative cases (p<0.001), with significantly higher levels in the former. These findings suggest that the circulation of hepatitis C virus among intravenous drug users has been decreasing in recent years, although new infections still occur. In agreement with the high rate of chronicization of parenterally transmitted hepatitis C, the majority of anti-HCV positive subjects had biochemical features of associated liver disease.     

Hepatitis C virus and depression in drug users

Objective: Clinical case studies have implicated depression as a possible side-effect of interferon treatment for the Hepatitis C virus (HCV). However, because these studies generally did not include a pretreatment assessment of depression, it cannot be definitively stated whether depression is a side-effect of interferon treatment, a syndrome coexisting with HCV, or a common characteristic of individuals who are vulnerable to HCV infection. To gather more information about this issue, self-reported depressive symptomatology of drug users with HCV who have not received interferon treatment was compared to that of uninfected drug users.
Methods: Subjects were 309 drug users not currently in substance abuse treatment who were participating in a National Institute on Drug Abuse project. Subjects completed the Center for Epidemiological Studies-Depression (CES-D) instrument and provided a blood sample for HCV testing.
Results: Serological findings revealed that 52.4% of the subjects tested positive for HCV antibodies. Of the HCV-positive subjects, 57.2% had significant depressive symptomatology, whereas only 48.2% of the HCV-negative subjects did, for an overall rate of 52.6%. The two groups also differed on two specific dimensions of depression, with the HCV-positive group scoring lower on the Positive Affect scale and higher on the Somatic/Retarded Activity scale.
Conclusions: These findings reveal high levels of depressive symptomatology among drug users, as well as the possibility of a coexisting depressive syndrome with HCV infection. These findings raise the possibility that depression associated with interferon treatment may, at least partially, be accounted for by preexisting depression. Further research is needed to determine the nature and origins of depression in individuals in treatment with interferon for HCV with specific focus placed on determining the dimensions of depression associated with HCV infection and interferon treatment.     

Hepatitis C virus load and survival among injection drug users in the United States

Persons chronically infected with hepatitis C virus (HCV), some of whom may be coinfected with HIV and human T-lymphotropic virus type II (HTLV-II), are at high risk for end-stage liver disease (ESLD). We evaluated whether ESLD death was associated with premorbid HCV RNA level or specific HCV protein antibodies among persons with or without HIV/HTLV-II coinfection in a cohort of 6,570 injection drug users who enrolled in 9 US cities between 1987 and 1991. We compared 84 ESLD descendents and 305 randomly selected cohort participants with detectable HCV RNA, stratified by sex, race, HIV, and HTLV-II strata. Relative hazard (RH) of ESLD death was derived from the proportional hazard model. Risk of ESLD death was unrelated to the intensity of antibodies against the HCV c-22(p), c-33(p), c-100(p), and NS5 proteins, individually or combined, but it increased with HCV RNA level (RH(adj) = 2.26 per log(10) IU/mL, 95% CI: 1.45-5.92). The association between HCV RNA level and ESLD death remained significant after adjustment for alcohol consumption (RH(adj) = 2.57 per log(10) IU/mL, 95% CI: 1.50-8.10). Deaths from AIDS (n = 45) and other causes (n = 43) were unrelated to HCV RNA (RH(adj)= 1.14 and 1.29 per log(10) IU/mL, respectively). HIV infection was not associated with ESLD risk in multivariate analyses adjusted for HCV RNA. Men had an increased risk of ESLD death in unadjusted analyses (RH = 1.92, 95% CI: 1.15-3.56) but not in multivariate analysis (RH(adj) = 0.98, 95% CI: 0.48-2.88). Non-black patients were at increased risk for ESLD death (RH(adj)= 2.76, 95% CI: 1.49-10.09). In conclusion, HCV RNA level is a predictor of ESLD death among persons with chronic HCV infection.     

Central nervous system infections in injection drug users

Central nervous system infections in injection drug users are often devastating in terms of excess morbidity and mortality. In injection drug users with infective endocarditis, embolization from infected valvular vegetations may cause cerebral infarction, intracranial hemorrhage, and the formation of brain abscess. Focal intracranial infections (i.e., brain abscess and spinal epidural abscess) may occur in the absence of infective endocarditis, resulting from bacteremia that seeds the brain or epidural space. Antimicrobial therapy, combined with surgical intervention, may be essential to improve outcome from these neurologic complications. Toxin-mediated diseases (especially tetanus and wound botulism) are also seen in injection drug users. Inoculation of Clostridium spp at injection sites may lead to toxin generation and disease. Clinicians must maintain a high level of suspicion for these diagnoses in injection drug users.     

Skin and soft tissue infections in injection drug users

Skin and soft tissue infections are the most common cause for hospital admission of injection drug users. Cutaneous and subcutaneous abscesses are the most frequent type of SSTI and occur most commonly when drug users are no longer able to inject intravenously and resort to injection directly into skin or muscle. Abscesses may be difficult to differentiate from uncomplicated cellulitis or may be confused with pseudoaneurysms, hematoma, phlegmon, or thrombosed vein. Special studies, including ultrasonography; CT scans, and MR imaging; or careful incision and inspection may be necessary to clarify the extent of infection and the presence of abscess. These procedures may also help differentiate a subcutaneous abscess from a vascular structure. Uncomplicated cellulitis most commonly responds to antibiotic therapy directed toward Staphylococcus aureus and Streptococcus spp. In several recent studies, cutaneous and subcutaneous abscesses have been found to be caused by polymicrobial infections and to include anaerobic organisms as well as aerobic gram-positive cocci in a little more than 50% of cases. Complete, often repeated, incision and drainage is a prerequisite for successful outcome in these cases. Complications of SSTI are many and are potentially life threatening. They include direct extension of subcutaneous abscess into vital areas or structures, necrotizing fasciitis and myositis, bacteremia, and sepsis. An outbreak of a highly lethal SSTI that recently occurred in Scotland, Ireland, and England seems to have resulted from infection with Clostridia spp, including C. novyi and C. perfringens. A rare but well-documented SSTI in injection drug users is pyomyositis, an abscess-forming infection of skeletal muscle. More than 20 cases have been reported in temperate climates to date. Although not life-threatening, chronic cutaneous venous ulcers of the lower extremities are common and debilitating, requiring long-term multidisciplinary care for successful healing.     

Program targets HIV+ injection drug users

A large intervention program designed specifically for HIV-positive injection drug users may provide HIV programs with a workable way to teach this population about safety measures.     

Hepatitis C and HIV infection: biological, clinical, and therapeutic implications

As deaths from AIDS continue to decline in HIV-infected persons, liver disease is becoming an increasing cause of hospital admission and death in HIV-HCV co-infected persons. The problem is particularly relevant among intravenous drug users and haemophiliacs, most of whom are co-infected. Moreover, the risk of hepatotoxicity is higher with anti-HIV drugs among patients with chronic hepatitis C. Treatment with alpha-interferon provides a similar rate of response in non-severely immunosuppressed HIV-positive subjects as in HIV-negatives, and preliminary results from trials using the combination of interferon plus ribavirin in HIV-HCV co-infection look very promising for both rates of sustained response and safety.