Effect of Baseline CD4 Cell Count on the Efficacy and Safety of Peginterferon Alfa-2a (40KD) Plus Ribavirin in Patients With HIV/Hepatitis C Virus Coinfection
The impact of baseline CD4 status on hepatitis C virus (HCV) treatment response among patients with HIV/HCV coinfection was investigated using data from a randomized study of peginterferon alfa-2a (40KD) + ribavirin (Peg-IFN/RBV).
Of 860 patients treated with conventional interferon alfa-2a + ribavirin (IFN/RBV), peginterferon alfa-2a (40KD) + placebo (Peg-IFN), or Peg-IFN/RBV for 48 weeks, 857 patients had baseline CD4 data available and were included in the analysis. Efficacy and safety were analyzed according to baseline CD4 status as absolute cell count and proportion of total lymphocytes.
Sustained virologic response (SVR) rates were highest with Peg-IFN/RBV across all CD4 strata. With Peg-IFN/RBV, SVR rates were independent of baseline CD4 in genotype 2/3 patients, but in genotype 1 patients, they tended to be higher with higher CD4 or CD4%. Frequencies of adverse events (AEs) and serious AEs were similar among treatment arms and CD4 strata. Withdrawal and dose reduction rates attributable to safety were highest with CD4 <200 cells/muL.
Peg-IFN/RBV could be effective and well tolerated in HIV/HCV-coinfected individuals with stable HIV. With Peg-IFN/RBV, response tended to increase with higher CD4 counts in genotype 1; however, because of the paucity of patients with CD4 <200 cells/muL, these data require corroboration.
Available from: Andrea Kovacs
- "Results of investigations of impact of baseline CD4 count on viral response kinetics are mixed. In a large randomized study of pegIFN + RBV in co-infected patients that included a small number of patients with CD4 counts <200 cells/μL, SVR rates tended to increase with higher CD4 counts in genotype 1, but were independent of baseline CD4 counts for genotypes 2/3 . Another large randomized study of co-infected patients found the efficacy of pegIFN + RBV was not different in patients with and without severe immunodeficiency, suggesting that advanced immunosuppression is not a major factor in predicting SVR . "
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ABSTRACT: World-wide, hepatitis C virus (HCV) accounts for approximately 130 million chronic infections, with an overall 3% prevalence. Four to 5 million persons are co-infected with HIV. It is well established that HIV has a negative impact on the natural history of HCV, including a higher rate of viral persistence, increased viral load, and more rapid progression to fibrosis, end-stage liver disease, and death. Whether HCV has a negative impact on HIV disease progression continues to be debated. However, following the introduction of effective combination antiretroviral therapy, the survival of coinfected individuals has significantly improved and HCV-associated diseases have emerged as the most important co-morbidities. In this review, we summarize the newest studies regarding the pathogenesis of HIV/HCV coinfection, including effects of coinfection on HIV disease progression, HCV-associated liver disease, the immune system, kidney and cardiovascular disease, and neurologic status; and effectiveness of current anti-HIV and HCV therapies and proposed new treatment strategies.
Available from: Martin Vogel
- "Therefore, if HIV infection is not advanced and there is no indication for HAART in the presence of high CD4-counts (> 500/μl), a treatment of chronic hepatitis C infection should be started prior to initiation of HAART . In a recent analysis of one of the largest studies on the treatment of HIV-infected with HCV infection, the APRICOT study, a relative CD4-cell count above 25% was associated with better treatment outcome than lower CD4-cell counts and initiation of HAART is strongly recommended prior to HCV therapy if the CD4-cell count is < 350/μl . Anti-HCV therapy in HIV co-infected individuals has been shown to be complicated by additive drug toxicities of pegylated interferon and ribavirin with the antiretroviral nucleosides didanosine [31,32], zidovudine [33-35] and stavudine . "
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ABSTRACT: Chronic HCV co-infection is present in up to one third of HIV-positive patients in Europe. In recent years, apart from the traditional transmission route of intravenous drug abuse, outbreaks of sexually transmitted acute HCV infections, mainly among HIV-positive men who have sex with men, have contributed to the overall disease burden.
Because the natural course of HCV infection is substantially accelerated in HIV-co-infection, end-stage liver disease has become the most frequent cause of non-AIDS related death in this population. Therefore every HIV/HCV co-infected patient should be evaluated for possible anti-HCV therapy with the goal of reaching a sustained virological response and thus cure of hepatitis C infection. The standard of care for the treatment of chronic HCV infection in HIV-infected remains a pegylated interferon in combination with weight-adapted ribavirin.
HAART should not be withheld from HCV co-infected patients due to concerns of drug related hepatotoxicity and in patients with reduced CD4-cell counts HAART should be started first. Under pegylated interferon and ribavirin combination therapy drug to drug interactions and cumulated toxicity between nucleoside analogues and anti-HCV therapy may be observed and concomitant didanosine use is contraindicated and zidovudine and stavudine should be avoided if possible.
The development of new drugs for the treatment of chronic hepatitis C represents a promising perspective also for HIV positive patients. However, these substances will probably reach clinical routine for HIV patients later than HCV monoinfected patients. Therefore at present waiting for new drugs is not an alternative to a modern pegylated interferon/ribavirin therapy.
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ABSTRACT: HIV, hepatitis C virus (HCV), and hepatitis B virus (HBV) infections are major public health problems. Patients at risk for
HIV infection are likely also at risk for HCV and HBV because of shared routes of transmission. HIV and antiretroviral therapy
(ART) have a significant impact on HCV and HBV. HIV coinfection accelerates HCV and HBV natural history, leading to an increased
incidence of cirrhosis, development of hepatocellular carcinoma (HCC), and death. Universal screening for HCV and HBV infections
in HIV-infected patients is essential. Proper screening combined with up-to-date treatment strategies can prevent these complications.
This review focuses on important aspects and recent developments in the rapidly evolving field of coinfection.
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