In co-infected HIV-HCV patients, HCV (HCV) viral load was higher than in plasma monochefe mono-infected HCV and liver tissue. HIV-positive patients are generally co-infected with HCV because of joint transmission routes: percutaneous exposure, sexual intercourse, and from mother to baby. HCV infection can be asymptomatic, self-limiting, or progress to cirrhosis or cancer.
Video Hepatitis C and HIV coinfection
Characteristics
Morbidity and mortality caused by HCV have increased since the inception of high antiretroviral therapy (ART) because HIV patients live longer than potent antiretroviral therapy and traditional opportunistic infection prophylaxis. The effect of HCV on HIV's natural history remains inconclusive because conflicting studies documented no effect, while others showed an increase in AIDS-defining illness or death. In the United States, about 150,000 to 300,000 people are coinfected with both HIV and HCV. It represents 15% to 30% of all HIV-infected patients and 5% to 10% of all HCV patients. Decreased production of HCV antibodies, drug interactions, other causes of liver disease, differences in epidemiological characteristics and natural history complicate the management of HCV/HIV patients. Until recently there has been little published data on treatment of HIV-HCV coinfected patients; fortunately recent trials have been published about the safety and efficacy of current treatment options.
Maps Hepatitis C and HIV coinfection
Treatment
The main goal of HCV therapy is the permanent eradication of the virus. The secondary potential benefits of eradication are reduced risk of liver failure and liver cancer. Currently, peginterferon alfa-2a plus ribavirin is the only FDA-approved treatment for HIV-HCV coinfected patients. Interferon binds to cell-specific cell-specific cell-cell receptors, which induce complex cascade interactions of proteins and rapid activation of gene transcription. Interferon antiviral effects mediated by inhibition of viral penetration or uncoating, inhibit viral replication or viral protein translation, and/or assembly and release of the virus. The difference between peginterferon and interferon is the addition of polymer polyethylene glycol (PEG). The addition of PEG significantly decreases plasma clearance, protects molecules from proteolytic degradation and reduces their immunogenicity. The peak concentration is about 1.5 to 2 times higher than the trough concentration and the half-life of 80 hours (compared to 5.1 hours for interferon alfa-2a). Ribavirin is a synthetic nucleoside analogue, but its mechanism of action is not clearly defined. Ribavirin inhibits the replication of RNA and DNA viruses. Pharmacokinetics are similar in patients coinfected with HIV compared with HCV mono-infection.
Pegylated Interferon Alfa -2B (Peg Intron) plus Ribavirin versus Interferon Standard Alfa-2B (Intron A) plus Ribavirin
This is a parallel, random, phase 3, open-label study. Four hundred and sixteen patients na na treatment were assigned to 1.5 Âμg/kg peginterferon alfa-2b once weekly plus ribavirin 800 mg per day or 3 million units of standard interferon alfa-2a plus ribavirin 800 mg per day for 48 weeks. 6 Patients were evaluated at weeks 2 and 4, then every 4 weeks after treatment and then at weeks 4, 12, and 24 post-treatment until week 72 was achieved. The primary endpoint was a sustained viral response (SVR), defined as an undetectable serum HCV-RNA at week 72. The secondary endpoint was a histologic improvement. In the standard interferon group, 20% of the 207 patients received SVR, and in the peginterferon group 27% of the 205 patients (p = 0.047) obtained SVR. At week 24, unreachable HCV RNA levels were achieved in 28% and 40% of patients, respectively (p = 0.004), respectively. At 48 weeks, the end of virological treatment response was 21% and 35% of the respective groups (p = 0.001). In patients with genotype 1 or 4, peginterferon achieved a higher SVR level (17%) than interferon (6%) p = 0.006. However, in genotype 2, 3 or 5, SVR levels are similar. Withdrawal rates and similar side effects.
Pegylated Interferon Alfa-2A (Pegasys) plus ribavirin versus Interferon Alfa-2A plus Ribavirin
In a study by Chung, et al. 66 patients taking treatment received a weekly 180 Âμg p response per week or 6 million units three times a week interferon for 12 weeks and then switched to 3 million units three times a week for 48 weeks. Both groups received ribavirin (600 mg for 4 weeks, 800 mg for four weeks and then 1000 mg daily for the remainder of the study). The primary endpoint was to detect differences in the rates of virological response between the two groups. At week 24, subjects who did not have a virologic response underwent liver biopsy and treatment continued in patients showing histologic improvement. Tolerability
In the first trial, approximately the same number of patients from each group withdrew due to laboratory abnormalities or side effects. Modified doses are more common in the peginterferon group due to laboratory abnormalities (7% vs 20%) or adverse events (7% vs. 16%) (p = 0.004). Neutropenia (p = 0.04) and weight loss (p = 0.03) were significantly higher in the peginterferon group; whereas, insomnia was higher in the interferon group (p = 0.02). In the second study, 12% in each group withdrew due to laboratory abnormalities or side effects. Both groups experienced the same number of episodes of neutropenia, but two subjects in the peginterferon group broke up due to level 4 neutropenia.
The other patients are managed by dose reduction. One case of clinically significant pancreatitis occurs in patients receiving ddI. In the last study, about the same number of patients who dropped out of the study due to laboratory abnormalities, but patients who dropped out of adverse reactions varied. Overall, most patients withdrew from interferon plus ribavirin and the least of the arms of peginterferon plus ribavirin.
The main difference is that there is a higher incidence of neutropenia in the peginterferon group.
Predictors of SVR
In the trials described above, the only common predictor of SVR among all three is HCV treatment other than type 1.6-8. In a trial by Chung et al. , the characteristics of patients predicting SVR are treatment. with peginterferon and ribavirin, no previous drug abuse, detectable HIV-1 viral load levels, and Karnofsky 100 score. Karnofsky's score is a subjective measure of how well patients do it. A score of 100 indicates that the patient has no complaints or evidence of the disease, a score of 50 indicates that the patient needs adequate help and frequent medical care, and a score of 0 indicates that the patient has died. In the study by Carrat et al., No PI therapy, age 40 years or younger, or basine alanine aminotransferase more than three times the upper limit of normal predicting virologic response persisted. In a study by Torrani et al. , SVR is predicted by HCV genotypes other than 1 and a baseline HCV RNA level of 800,000 IU or less per milliliter.
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