Management and treatment of injection drug users with hepatitis C virus (HCV) infection and HCV/human immunodeficiency virus coinfection

Injection drug use is the major mode of hepatitis C virus (HCV) transmission in developed countries. Despite this, relatively few current and recovering injection drug users (IDUs) have received HCV treatment. Studies among individuals with a recent history of injection drug use or those receiving drug dependency treatment have provided evidence that these groups can be successfully treated for chronic HCV infection. These studies have provided the impetus to change guidelines for treatment of current and recovering IDUs, with a move toward individualized HCV treatment assessment and the removal of defined periods of illicit drug use abstinence. Strategies to improve access to HCV treatment for current and recovering IDUs include drug dependency treatment education and training for hepatologists and other HCV treatment physicians, HCV treatment education and training for addiction medicine physicians, development of multidisciplinary clinics, and peer-based eduction and support for individuals considering and receiving HCV treatment.     

Absence of chronic human immunodeficiency virus infection without seroconversion in intravenous drug users: a prospective and retrospective study

It has been reported that human immunodeficiency virus type 1 (HIV-1) infection may exist in persons without specific antibodies for years. To measure the frequency of a silent carrier state, a study was conducted in a cohort of 124 intravenous drug users (IVDUs) without anti-HIV-1 antibodies. All the participants had engaged in high-risk behavior for HIV-1 transmission for a number of years until 1987 or later. Samples were analyzed at 6-month intervals for the presence of HIV-1 provirus using DNA amplification and for the appearance of anti-HIV-1 antibodies. HIV-1 provirus and antibodies were undetectable in 122 participants, whereas seroconversion was observed in 2. In one of these, both amplified HIV-1 pol gene segment and anti-HIV-1 antibodies were detected simultaneously, and in the other, provirus was detected 1 month before seroconversion. This study suggests that long-term HIV-1 infection without anti-HIV-1 antibodies is rare and that repeated antibody testing is sufficient to determine the HIV-1 status of a person no longer at high risk for HIV-1 infection.     

Frequent hepatitis C virus superinfection in injection drug users

The frequency of hepatitis C virus (HCV) superinfection with a divergent viral strain was determined in a cohort of recently infected young injection drug users (IDUs) with an HCV incidence rate of 25%. HCV was amplified, by use of polymerase chain reaction (PCR), from plasma samples collected from 25 HCV-infected individuals over an average period of 12 months, and their viral sequences were compared. Phylogenetic analysis identified 5 IDUs with superinfection (20%) occurring after seroconversion: 2 IDUs were superinfected with different HCV genotypes, and 3 were superinfected with divergent strains of the same genotype. The superinfecting strains were not detected as minority variants (<0.5%) in the initial plasma HCV quasi species. Extensive measures were taken to exclude PCR contamination and mix-up of samples, and superinfection results were concordant at 2 HCV genetic loci. HCV superinfection in IDUs, both intra- and intergenotype, is therefore a frequent event, with an incidence rate similar to that of de novo infections. These results suggest that no cross-protecting immunity develops during the first year of chronic infection with HCV.     

Increased hepatitis C virus load among injection drug users infected with human immunodeficiency virus and human T lymphotropic virus type II

Coinfection of hepatitis C virus (HCV) and human immunodeficiency virus (HIV) and/or human T-lymphotropic virus type II (HTLV-II) is common among drug users. We compared HCV RNA detection and load in a cohort of 6570 injection drug users from 9 US cities during 1987-1991. Of 385 subjects selected from 16 strata by sex, race (black or nonblack), and HIV/HTLV-II group (HIV positive [HIV(+)]/HTLV-II(+), HIV(+)/HTLV-II negative [HTLV-II(-)], HIV(-)/HTLV-II(+), and HIV(-)/HTLV-II(-)), 376 had HCV antibodies, of whom 305 had detectable HCV load. HCV RNA detection was unrelated to sex, race, and virus groups, but differed by study site. The mean HCV load was 5.4 log(10) IU/mL and was 0.24 log(10) higher in men than in women. Virus load increment with HIV or HTLV-II infection was higher among white subjects than among other subjects. Compared with HIV(-)/HTLV-II(-) subjects, virus load was 0.50, 0.22, and 0.56 log(10) higher in HIV(+)/HTLV-II(-), HIV(-)/HTLV-II(+), and HIV(+)/HTLV-II(+) subjects, respectively. HTLV-II infection significantly increased HCV load in white subjects but not in other racial groups.     

Understanding human immunodeficiency virus type 1 and hepatitis C virus coinfection

In recent years, there has been an alarming increase in the number of cases of coinfection with the human immunodeficiency virus type 1 (HIV-1) and the hepatitis C virus (HCV). It is now known that coinfection of HIV-1 patients by HCV can complicate the treatment of these patients with highly active antiretroviral therapy and the interactions between anti-HIV-1 and anti-HCV medications can also affect treatment efficacy and efficiency. Equally concerning, the bidirectional interferences between the two viruses are complex and can modify the natural history of both infections. This review aims to summarize the findings of numerous scientific investigations in the area of HIV/HCV coinfection. These investigations can be broadly classified into 3 groups; (a) immune evasion mechanisms (b) viral evolution and quasispecies diversity and (c) functions of viral proteins and their interactions with host factors. Our cumulative knowledge in this area and future research on the interplay between these two viruses will be important to the development of better antiviral therapeutics.     

Intrafamilial transmission of hepatitis C virus in patients with hepatitis C and human immunodeficiency virus coinfection

OBJECTIVE: The aim of this study was to determine whether hepatitis C virus (HCV)/HIV coinfection of index cases increases intrafamilial transmission (sexual and nonsexual contacts) of HCV. METHODS: We prospectively enrolled 347 subjects, including 87 family members of 53 HCV/HIV-coinfected index cases and 134 family members of 73 HCV-monoinfected index cases, which served as a control group. All index cases and family members were interviewed, and a screening for HCV and HIV using enzyme-linked immunosorbent assays was performed. Positive samples were confirmed by polymerase chain reaction and tested for genotype and HCV RNA viral load. A meta-analysis designed to assess the pooled risk of sexual transmission of HCV among HCV/HIV-coinfected patients was performed. RESULTS: Anti-HCV was detected in 2.2% of family members of HCV-monoinfected index cases and 2.3% of family members of HCV/HIV-coinfected index cases. Viral load was higher in coinfected index cases (7.2 x 10(6) mEq/ml) compared with HCV alone (1.9 x 10(6) mEq/ml), p = 0.01. HCV genotype concordance was observed in three family members of HCV-monoinfected index cases and in two family members of HCV/HIV-coinfected index cases. The pooled OR of the meta-analysis evaluating HIV as a cofactor of sexual transmission of HCV was 1.54 (95% CI = 0.76-3.12). CONCLUSIONS: Our data demonstrate a low prevalence of intrafamilial transmission of HCV, independent of the presence of HCV/HIV coinfection. This finding is supported by meta-analysis, which failed to identify HIV as an important cofactor of sexual transmission in HCV/HIV-coinfected patients.     

人类免疫缺陷病毒感染者合并丙型肝炎病毒感染的危害性及治疗策略

随着高效抗逆转录病毒治疗(highly active antiretroviral therapy,HAART)在临床上的广泛开展,HIV/AIDS患者的生存时间显著延长.据估计,如果患者血浆HIV能在治疗后得到完全控制,其预期寿命能超过30～40年甚至更长.目前AIDS已成为一种像高血压或糖尿病那样无法完全根治,但可以在药物治疗下长期存活的慢性疾病.     

Prevalence of coinfection with human immunodeficiency virus and hepatitis C virus in Japan

People with human immunodeficiency virus (HIV) infection are frequently infected with hepatitis C virus (HCV), because of the common transmission routes. Since the dissemination of hyperactive antiretrovirus therapy (HAART), the morbidity and mortality associated with HIV infection have declined. However, the reduction in mortality due to opportunistic infection has made HCV-associated liver diseases the leading cause of mortality in Western countries. A similar situation is assumed in Japan, but the status of coinfection with HIV and HCV is unclear. We conducted a nationwide survey to determine the prevalence of coinfection with HIV and HCV by distributing a questionnaire to the hospitals in the HIV/AIDS Network of Japan. Among 4877 patients reported to be HIV-positive, 935 (19.2%) were also positive for the anti-HCV antibody. Most (84.1%) of the patients coinfected with HIV and HCV were recipients of blood products. These data, for the first time, show the current status of coinfection with HIV and HCV in Japan. A detailed analysis of the progression and severity of liver diseases in the coinfected patients is expected.     

The impact of hepatitis C coinfection on kidney disease related to human immunodeficiency virus (HIV): a biopsy study

Approximately 1 in 4 individuals infected with the human immunodeficiency virus (HIV) in the United States is coinfected with the hepatitis C virus. Both conditions increase the risk for the development and progression of kidney disease. The effect, however, of coexisting HIV and hepatitis C infection on the spectrum and progression of kidney disease is not well known. To compare the clinical features, histopathologic kidney diagnoses, and proportion of individuals progressing to end-stage kidney disease (ESKD), we reviewed the clinical records of HIV-infected individuals with and without hepatitis C coinfection who underwent ultrasound-guided percutaneous kidney biopsies between February 7, 1995, and March 30, 2009.Of the 249 HIV-infected individuals included in this study, 58% were coinfected with hepatitis C. Coinfected individuals were older (mean age, 46 ± 7 vs. 44 ± 10 yr, respectively; p < 0.01) and more likely to have used illicit drugs (85% vs. 14%, respectively; p < 0.01) compared to HIV-infected individuals without hepatitis C. HIV-associated nephropathy was the most common histopathologic diagnosis in both groups. Immune-complex glomerulonephritides (ICGNs), including lupus-like nephritis, postinfectious glomerulonephritis, membranous glomerulopathy, membranoproliferative glomerulonephritis, IgA nephropathy, and nonspecific ICGNs, occurred more frequently in individuals coinfected with hepatitis C than in those not coinfected (22% vs. 11%, respectively; p = 0.02). Although the proportion of those who died was similar between the 2 groups, hepatitis C coinfection was independently associated with a greater risk of progression to ESKD (hazard ratio, 1.81; 95% confidence interval, 1.09-2.99; p = 0.02).The current study demonstrates that coinfection with hepatitis C in individuals infected with HIV predisposes these individuals to immune-complex glomerulonephritides and is associated with increased risk of ESKD in the biopsied population.     

Liver enzyme values in injection drug users with chronic hepatitis C

BACKGROUND: Liver enzymes fluctuate in chronic hepatitis C virus infection. However, the range that can be attributed to the course of hepatitis C virus (versus an intercurrent cause of hepatitis) is unknown. AIMS: To characterise the range of liver enzyme values as a function of the upper limit of normal (ULN) of the assay among persons chronically infected with hepatitis C virus. PATIENTS: One thousand and fifty-nine hepatitis C virus chronically infected individuals with > or =5 semi-annual evaluations. METHODS: Alanine aminotransferase and aspartate aminotransferase levels were prospectively obtained. Potential causes of elevations were examined using serologic testing. RESULTS: Among 1059 individuals, 11,463 enzyme measurements were obtained over 6.5 years, of which 63.5% were <1.25x ULN, 26.5% were 1.25-2.5x ULN, 8.3% were 2.5-5x ULN, and 1.6% were 5-10x ULN; only 0.2% were >10x ULN. Elevations >10x ULN were transient, the alanine aminotransferase/aspartate aminotransferase ratio tended to be different at the time of the elevation compared to before and after and 24% were associated with acute viral hepatitis. On the other hand, subjects with elevations 5-10x ULN tended to have elevated levels throughout follow-up and only 8% were associated with acute viral hepatitis. CONCLUSIONS: Liver enzymes fluctuate up to 5x ULN in most hepatitis C virus-infected persons; clinicians should seek alternate explanations for those with higher alanine aminotransferase or aspartate aminotransferase levels, especially among hepatitis C virus-infected persons with greater than 10-fold elevations.     

Detection of multiple hepatitis C virus genotypes in a cohort of injecting drug users

Multiple genotypes of the hepatitis C virus (HCV) were detected in five of 138 HCV RNA positive injecting drug users (IDUs) recruited in Melbourne, Australia. Two were detected by combined LiPA and core and NS5a region sequencing, and three more (selected for testing due to their high-risk behaviour) by heteroduplex mobility analysis. We conclude that the true prevalence of mixed infection in IDUs is undoubtedly higher than the 3.6% (five of 138) we observed, and is underestimated by LiPA, the most common method of genotyping. As responsiveness to HCV treatment varies significantly with genotype, a high prevalence of mixed HCV infections in IDUs must diminish overall treatment efficacy and lessen our ability to reduce the burden of HCV-related disease.     

High incidence of hepatitis C virus reinfection in a cohort of injecting drug users

An estimated 170 million people worldwide carry the hepatitis C virus (HCV), and in more developed countries the prevalence and incidence of HCV is particularly high among injecting drug users (IDUs). Spontaneous clearance of HCV infection and reinfection is well recognized but the level of protection against further infection conferred by HCV infection and clearance remains uncertain. We conducted a prospective study of HCV infection in IDUs recruited in Melbourne, Australia, using a much shorter median testing interval than in previous studies. Incidences of naive infection and reinfection were calculated by the person-year method and Cox proportional hazards regression used to adjust for covariates. A significantly higher HCV incidence rate was measured in previously infected IDUs (46.8% per year) compared with HCV-naive IDUs (15.5% per year). The hazard ratio for previously infected IDUs compared to HCV-naive IDUs, after adjustment for time-dependent covariates, was 2.54 (95% confidence interval, 1.11-5.78, P > |z| < 0.05). Viral persistence after reinfection appeared similar to that following naive infection. Conclusion: Our data suggest that HCV infection in IDUs is more likely following prior infection and clearance than in HCV-naive individuals, implying no increased immunity against further infection. This result has important implications for the future development of an HCV vaccine.     

人类免疫缺陷病毒和丙型肝炎病毒共感染患者肝硬化发病情况

目的探讨人类免疫缺陷病毒(HIV)和丙型肝炎病毒(HCV)共感染患者发展到肝硬化的情况及原因。方法将观察对象分为HIV和HCV共感染组、单独HCV感染组。回顾性比较HIV和HCV共感染患者、单独HCV感染患者15年内发展到肝硬化的情况。结果HIV和HCV共感染患者15年内肝硬化发生率为16.4％(23／140)明显高于单独HCV感染组3.0％(1／33),差异有统计学意义,x2=4.012,P=0.045。CD4+、CD8+T淋巴细胞计数在HIV和HCV共感染组分别为(200.0±134.1)个／μl及(880.6±444.2)个／μl,而单独HCV感染组分别为(752.3±251.7)个／μl及(529.0±170.7)个／μl,两组比较差异有统计学意义,t值分别为12.020和7.600,P值均<0.01;HCVRNA(+)、抗HCV(+)数与HCVRNA(+)、抗-HCV(-)数,在HIV和HCV共感染组为89例和15例,在HCV感染组为25例和0例,两组间差异有统计学意义,x2=4.080,P=0.043。结论HIV和HCV共感染可加速肝硬化的进展,可能与HIV对机体的细胞免疫、体液免疫有关。     

Molecular epidemiology of hepatitis C virus in a social network of injection drug users

BACKGROUND: We aimed to measure the overlap between the social networks of injection drug users (IDUs) and the patterns of related hepatitis C virus (HCV) infections among IDUs. METHODS: A cohort of 199 IDUs (138 of whom were HCV RNA positive) was recruited from a local drug scene in Melbourne, Australia, and was studied using social network analysis and molecular phylogenetic analysis of 2 regions of the HCV genome. RESULTS: Eighteen clusters of related infections involving 51 IDUs (37.0% of HCV RNA-positive IDUs) were detected; these clusters could be separated into 66 discrete pairs. Twelve (18.2%) of the 66 IDU pairs with related infections reported having previously injected drugs together; conversely, only 12 (3.8%) of the 313 pairs of HCV RNA-positive IDUs who were injection partners had strong molecular evidence of related infections. The social and genetic distances that separated IDUs with identical genotypes were weakly associated. Significant clusters of phylogenetically related sequences identified from core region analysis persisted in the analysis of the nonstructural 5a protein region. Genotyping and sequence analysis revealed 2 mixed-genotype infections. CONCLUSIONS: Static social network methods are likely to gather information about a minority of patterns of HCV transmission, because of the difficulty of determining historical infection pathways in an established social network of IDUs. Nevertheless, molecular epidemiological methods identified clusters of IDUs with related viruses and provided information about mixed-genotype infection status.