Heterosexual co-transmission of hepatitis C virus (HCV) and human immunodeficiency virus (HIV).

OBJECTIVES: To determine the prevalence of antibodies to hepatitis C virus (HCV) in female sexual partners of multitransfused men with hemophilia and to compare the frequency of transmission of HCV and human immunodeficiency virus (HIV). STUDY DESIGN: Cross-sectional measurement of HCV and HIV antibodies. SETTING: Ten hemophilia treatment centers. PATIENTS: A total of 234 female sexual partners of 231 multitransfused men with hemophilia. MEASUREMENTS AND MAIN RESULTS: The prevalence of antibodies to HCV (anti-HCV) among female sexual partners of HCV-positive men was 5 of 194 (2.6%). Anti-HIV prevalence among female sexual partners of HIV-positive men was 25 of 196 (12.8%). Five (3%) of the 164 female sexual partners of HIV-positive/HCV-positive men were infected with HCV compared with none of the 30 female sexual partners of HIV-negative/HCV-positive men. Twenty-one (13%) of the 164 female sexual partners of HIV-positive/HCV-positive men were infected with HIV compared with 4 (13%) of 32 female sexual partners of HIV-positive/HCV-indeterminate men. The co-infected men were five times more likely to transmit both viruses than would be expected by chance (P = 0.01). When a single virus was transmitted to a female sexual partner, it was more often HIV than HCV (18 of 164 compared with 2 of 164, P = 0.001; odds ratio, 8.5; 95% Cl, 2.2 to 33.1). CONCLUSIONS: The higher prevalence of HCV in female sexual partners of men with hemophilia than in blood donor and other low-risk groups suggests that there is a low level of sexual transmission. Male to female sexual transmission of HCV is less efficient than that of HIV. The frequency of HCV transmission to sexual partners is five times higher when HIV is also transmitted, suggesting that HIV may be a cofactor for the sexual transmission of HCV.     

Low levels of hepatitis C virus (HCV) neutralizing antibodies in patients coinfected with HCV and human immunodeficiency virus

The hepatitis C virus (HCV) neutralizing antibody (nAb) response in 37 subjects with HCV monoinfection and 37 HCV-infected subjects with well-controlled human immunodeficiency virus (HIV) infection was evaluated using a focus reduction neutralization assay. HCV nAb levels were retrospectively studied in both groups of patients, who were matched on the basis of sex, age, and HCV genotype. The mean HCV nAb level (+/- standard deviation) among coinfected patients (1.613+/-0.416) was significantly less than that among monoinfected patients (1.912+/-0.578) (P= .013). Lower HCV nAb titers in coinfected patients could help worsen the outcome of HCV infection. These results favor starting HCV therapy as soon as possible in coinfected patients.     

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.     

Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) dynamics during HCV treatment in HCV/HIV coinfection

We studied hepatitis C virus (HCV) and human immunodeficiency virus (HIV) dynamics in 10 coinfected subjects in a trial of pegylated interferon-alpha2a (PEG-IFN) alone or combined with ribavirin (RBV), compared with IFN plus RBV for the treatment of HCV. Five subjects, 4 of whom were treated with PEG-IFN, achieved a sustained virological response, although it was delayed by >/=1 week in 3 subjects. The median treatment efficacy in blocking virion production was 99.7% in the PEG-IFN group and 60% with standard IFN. In 2 patients with detectable HIV loads before starting HCV study drugs, we observed a 1-log decrease in HIV RNA load. The estimated HCV virion half-life was longer in the HIV-coinfected subjects, which suggests that coinfection may contribute to a slower clearance of HCV. Although the early viral kinetics of coinfected subjects treated with PEG-IFN or IFN differ from those of singly infected subjects, the treatment response seems unaffected.     

The extrahepatic manifestations in hepatitis C virus (HCV) infection

The hepatitis C virus (HCV) infection could affect not only the liver, but also other tissues, organs and systems. The number of the reported in the literature extrahepatic lesions by HCV incessantly increases. A reliable association between the infections by HCV and the mixed cryoglobulinaemias, membrano-proliferative glomerulonephritis and porphyria cutanea tarda is confirmed. The participation of HCV in the pathogenesis of some diseases of the thyroid gland, the lymphocytic sialadenitis, lichen planus, diabetes mellitus, thrombocytopenia, antiphospholipid syndrome, etc., is assumed. The extrahepatic lesions by HCV are probably connected with the participation of the immune system, but they may be as well due to the replicating virus in the affected tissues, organs and systems. The pathogenetic mechanisms of the extrahepatic and autoimmune manifestations of the infection with HCV are not elucidated, which poses difficult therapeutic problems regarding the choice of interferon and/or corticosteroid hormones.     

Expression of hepatitis B virus (HBV) markers in chronic liver disease positive for antibody to hepatitis C virus (HCV)

We investigated expression of HBV markers in chronic liver disease positive for antibody to HCV (anti-HCV). Sera from 107 patients with chronic non-A, non-B liver disease, 65 HBs antigen carriers with chronic liver disease and 14 asymptomatic HBV carriers were tested for the presence of anti-HCV. Anti-HCV was detected in 83 (78%) patients with chronic non-A, non-B liver disease, irrespective of the past history of blood transfusion, and anti-HCV prevalence was similar in each category of chronic liver disease. Fifty-three (64%) out of these 83 sera positive for anti-HCV has also antibodies to HBV. Anti-HBc antibody was detected frequently in liver cirrhotics with hepatocellular carcinoma than in chronic persistent hepatitis, chronic active hepatitis and cirrhotics without hepatocellular carcinoma. In addition, titers of anti-HBc antibody were significantly higher in cirrhotics with hepatocellular carcinoma than in the other groups. On the other hand, anti-HCV was detected in 7 out of 65 patients with HBV-related liver disease. Four out of these 7 were patients with HBV-related hepatocellular carcinoma. Anti-HCV was detected in none of asymptomatic HBV carriers. These findings suggest that infection with both HBV and HCV is likely to cause more serious liver disease than infection with a single agent.     

Absence of human T-cell lymphotropic virus type I coinfection in human immunodeficiency virus-infected hemophilic men

Concern for transmission of human T-cell lymphotropic virus, type 1 (HTLV-1) infection to recipients of infected cellular blood products has prompted development of tests to eliminate blood units with HTLV-I antibodies. Most hemophilic men from the United States became infected with human immunodeficiency virus (HIV) before HIV donor screening and before blood products were processed to inactivate the virus. To assess whether these men might also be infected with HTLV-I, we examined the HTLV-I antibody status of 127 factor VIII (hemophilia A) recipients and 71 factor IX (hemophilia B) recipients. One HIV-seronegative and four HIV-seropositive persons were HTLV-I reactive by enzyme-linked immunosorbent assay (ELISA). Four of five ELISA-reactive serum samples were negative by HTLV-I immunoblot assay (IB); 1 reactive and 1 borderline reactive serum were indeterminate on IB (p19 reactivity), but negative by radioimmunoprecipitation assay (RIPA). Peripheral blood mononuclear cells from one patient with indeterminate HTLV-I IB were negative for HTLV-I genomic sequences by polymerase chain reaction. The other indeterminate patient's serum antibody pattern was stable over a 2-year period, suggesting this was not an instance of early HTLV-I seroconversion. These results reaffirm the safety of factor components in the United States with regard to HTLV-I but emphasize the importance and need for further testing of reactive HTLV-I ELISA results with a second more specific technique.     

Compartmentalization of hepatitis C virus (HCV) during HCV/HIV coinfection

Extrahepatic replication has important implications for the transmission and treatment of hepatitis C virus (HCV). We analyzed longitudinal HCV diversity in peripheral-blood mononuclear cells (PBMCs) and serum during HCV monoinfection and HCV/HIV coinfection to determine whether distinct amino acid signatures characterized HCV replicating within PBMCs. Analysis of E1-HVR1 sequences demonstrated higher serum genetic distances among HCV/human immunodeficiency virus (HIV)-coinfected persons. Moreover, consensus PBMC sequences were rarely identical to those in the corresponding serum, suggesting divergence in these 2 compartments. Three of 5 HCV/HIV-coinfected participants showed evidence of HCV compartmentalization in PBMCs. Additionally, signature sequence analysis identified PBMC-specific amino acids in all HCV/HIV-coinfected persons. To our knowledge, this is the first study to identify specific amino acids that may distinguish HCV variants replicating in PBMCs. It is provocative to speculate that extrahepatic HCV diversity may be an important determinant of treatment response and thus warrants additional study, particularly during HCV/HIV coinfection.     

Patients co-infected with human immunodeficiency virus and hepatitis C virus demonstrate higher levels of hepatic HCV RNA

Serum and liver hepatitis C virus (HCV) RNA levels in patients with hepatitis C have previously been quantified using different techniques. In this work, we used an automated, multicycle, polymerase chain reaction (PCR)-based technique to quantify HCV RNA in 1-2 mm of frozen liver tissue, and in serum, from 70 patients with antibodies to HCV (anti-HCV), with and without human immunodeficiency virus (HIV) co-infection. Stored liver tissue and sera collected at the time of liver biopsy were used for measurement of HCV RNA. Forty-eight HCV patients and 22 HIV/HCV co-infected patients were studied. Co-infected patients had significantly higher median serum and liver HCV RNA (6.7 log copies ml-1 serum and 2.90 log copies microg-1 liver nucleic acids) than patients with HCV alone (6.2 log copies ml-1 serum and 2.19 log copies microg-1 liver nucleic acids). There was only a weak correlation between serum and liver HCV RNA (r = 0.43). There was no correlation between liver and serum HCV RNA and host factors such as duration of disease, CD4 counts, alanine aminotransferase levels or histological score. There was no correlation with HCV genotype. Co-infected patients were more likely to harbour HCV genotype 1 (85%) when compared to patients with HCV alone (58%). An identical genotype was found in liver and serum in 89% of those tested; in 11%, a mixed genotype was present in serum. Patients with HCV genotypes 1 and non-1 had similar histological scores. Hence, an automated PCR-based technique is useful for measuring both liver and serum HCV RNA. Serum HCV genotypes closely paralleled those found in liver tissue. HIV co-infection was associated with higher serum, as well as intrahepatic, HCV RNA levels, by mechanisms not directly related to CD4 counts. The lack of correlation between liver HCV RNA and histology suggests that HCV is not directly cytopathic.     

Liver histology in co-infection of hepatitis C virus (HCV) and hepatitis G virus (HGV)

As little is known about liver histology in the co-infection of hepatitis C virus (HCV) and hepatitis G virus (HGV), HGV RNA was investigated in 46 blood donors with hepatitis C, 22 of them with liver biopsy: co-infection HCV / HGV (n = 6) and HCV isolated infection (n = 16). Besides staging and grading of inflammation at portal, peri-portal and lobular areas (Brazilian Consensus), the fibrosis progression index was also calculated. All patients had no symptoms or signs of liver disease and prevalence of HGV / HCV co-infection was 15.2%. Most patients had mild liver disease and fibrosis progression index, calculated only in patients with known duration of infection, was 0.110 for co-infection and 0.130 for isolated HCV infection, characterizing these patients as "slow fibrosers". No statistical differences could be found between the groups, although a lesser degree of inflammation was always present in co-infection. In conclusion co-infection HCV / HGV does not induce a more aggressive liver disease, supporting the hypothesis that HGV is not pathogenic.     

Treatment of chronic hepatitis C virus infection in human immunodeficiency virus (HIV) infected patients

Treatment of chronic hepatitis C Virus (HCV) infection in human immunodeficiency virus (HIV) infected patients has become a topic of great importance, since the complications of chronic hepatitis are the first one cause of mortality among HIV patients. The aim of this study is to review the biological and epidemiological data in HIV-HCV coinfection, to establish treatment guidelines taking in consideration drugs' adverse effects and interactions, and to report the results of the main studies carried out. The treatment currently accepted includes pegylate interferon andribavirin, which have improved prior treatments, but the response rate depends on HCV genotype.     

CD4 T lymphocyte proliferative responses to hepatitis C virus (HCV) antigens in patients coinfected with HCV and human immunodeficiency virus who responded to anti-HCV treatment

CD4 T lymphocyte proliferative responses to hepatitis C virus (HCV) antigens were evaluated before and during an anti-HCV regimen (interferon-alpha2a and ribavirin) in 36 patients coinfected with HCV and human immunodeficiency virus (HIV), to determine whether immune responses against HCV antigens are present in such patients, whether these responses are modified by anti-HCV treatment, and whether they are correlated with treatment efficacy. The CD4 responses against HCV antigens (primarily core antigens) detected at study entry in one-half of the patients did not correlate with anti-HCV treatment efficacy. Of 36 patients, 8 had patterns of persistent immune response to infection by genotypes 3 or 4 that were significantly correlated with sustained virologic response. Persistent immunologic reactivity and sustained virologic response coexisted only in patients infected with genotype 3. These findings suggest that HCV genotype may influence specific immune response, which, in turn, is implicated in virologic control.     

Interferon treatment of two patients with quadruple infection with hepatitis C virus (HCV), human immunodeficiency virus (HIV), hepatitis G virus (HGV), and TT virus (TTV)

Abstract: We administered interferon (IFN) to two patients who had quadruple infection with hepatitis C virus (HCV), human immunodeficiency virus (HIV), hepatitis G virus (HGV), and TT virus (TTV), a recently isolated novel DNA virus. Nine mega-units of natural alpha-IFN were administered daily during the first two weeks and thrice weekly during the following 22 weeks (total dose, 720 mega-units). In both cases, serum alanine aminotransferase (ALT) levels decreased during IFN administration but increased thereafter. The concentrations of HCV, HIV, HGV, and TTV declined with the administration of IFN. However, the concentrations of these 4 viruses increased after the cessation of IFN with the except of TTV in patient 2 which disappeared during treatment and did not subsequently reappear. IFN reduced the concentrations of 4 viruses, in an apparently independent manner.