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Management of Hep C in HIV-infected Persons in the USA
Presentation by David Thomas, MD, Dept of Infectious Diseases, Johns Hopkins University Medical School |
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Preliminary Full Draft Statement from the NIH
http://consensus.nih.gov/cons/116/116cdc_intro.htm
Comments can be submitted on the draft up until June 19 to
Kelli Marciel (301) 496-4819, NIH office of Medical Research, email:
marcielk@od.nih.gov
In brief, Thomas recommended that the Consensus Statement support treatment of HCV for HIV-infected patients. He said coinfected patients can respond well to HCV therapy. They can achieve good viral responses and the level of adverse events appear similar to those with HCV alone. HIV appears to accelerate HCV progression, so the urgency for HCV therapy may be greater in coinfected patients. He alluded to the concern that in many communities HIV-infected patients are not being tested for HCV. Obviously, meaning care and treatment are not available. Since HIV can accelerate HCV this delay in treatment may be more harmful to HIV-infected patients.
Thomas started by saying HCV is an important problem in people with HIV. In his talk, Thomas said an estimated that about 200,000 individuals with HIV also have HCV. (Based on ACTG data). About 1 in 4 of HIV-infected. In urban areas such as in Baltimore 50-90% of IVDUs have HC. Others have estimated 30-40% have coinfection. As health has improved and longevity increased due to ART in HIV, Hep C has emerged as a leading cause of death in HIV and in some settings is the leading cause of death.
Initially Thomas said in his talk that the quantitiy and quality of the data from reported studies in treating coinfected patients is so far not as great as we would like. But he emphatically stated that we should not let this uncertainty impede us from strongly supporting treatment for coinfected patients, because the burden of disease is high. HIV probably affects adversely each of the stages of progression of HCV. It probably increases the proportion of patients who will get cirrhosis and probably shortens the duration of time itıll take to reach cirrhosis. There is some data showing an increasing proportion of those with cirrhosis will develop HCC or ESLD over a shorter period of time. Unfortunately, the data in trying to understand the frequency with which these outcomes will occur and in trying to estimate the time it will take to reach certain stages is uncertain, as there are a number of studies with variable estimates. It is difficult to make estimates for individual patients. It is difficult to sit with a patient and predict their rate of progression even if their liver biopsy results are available. Nonetheless, some estimates are available and the best come from this meta-analysis. In this study they estimated the risk of progression to cirrhosis was increased 2-fold in HIV/HCV coinfected patients. And the risk of developing end stage liver disease was elevated about 6-fold. This data comes from patients chiefly with hemophilia. In summary, the risk for increased disease progression is increased in HIV/HCV coinfected patients, and from the perspective of disease progression alone this certainly increases the urgency of treatment.
US Health Service Guidelines recommend all HIV-infected persons be tesed for HCV with antibody test and followed by for confirmation and evaluation with PCR. Thomas said there appear to be some differences in transmission risk when HIV is present and he mentioned that there is some data showing that HIV increases HCV transmission, but he recommended that the recommendations regarding transmission of HCV when HIV is present are sufficient. I may disagree with him on this. I agree that the data on transmission are unclear but I think that based on available data it suggests there may be increased risk for HCV transmission in several ways when HIV is present. In addition, STDs may be more likely to be present in HIV-infected persons and although the data is not clear it suggests that risk of HCV transmission may be increased when STDs or open sores such as HSV-2 are present. So, I think caution should be advised.
In deciding who to treat and how HIV-infected patients should be treated one should consider the likelihood for disease progression, the likelihood that disease progression can be stopped (eradication) or slowed with the potential for adverse effects of treatment and the likelihood that something else may kill the patient. He made reference to the fact that with the use of HAART the likelihood of patients dying from HIV is greatly diminished. I want to add here that longevity and the potential for much longer liver is greatly improved. Many call HIV now a chronic manageable disease. This greatly increases the need to offer timely HCV testing and accessible and effective treatment and support services to coinfected patients.
Thomas said that the FDA has not yet approved interferon+rbv for coinfected patients and there are no published data on pegylated interferon plus ribavirin in coinfected patients showing sustained responses. I think he meant the data is short-term. But, he said there are several important considerations. First, you can cure a patient, a cure is possible. Sustained viral responses have been shown in studies even with interferon monotherapy. Data presented from studies at science conferences show the addition of ribavirin increases at least the on-treatment responses for coinfected patients. He presented the week 24 preliminary results from ACTG study 5071, a multi-center, randomized study. This data was presented at the 2002 Retrovirus Conference. 134 coinfected patients on stable HIV therapy and with stable HIV were randomized to receive either Pegasys+ribavirin or standard interferon plus ribavirin. Biopsies were obtained at baseline. Treatment will be for 48 weeks. Baseline characteristics for the two treatment groups were similar. A better response (undetectable HCV RNA) was achieved for patients receiving Pegasys plus ribavirin (44% vs 15%) at week 24. This was true for patients with both genotype 1 and 2. This suggests that Pegasys will be better for patients with coinfection, as it is for patients with HCV alone. There is preliminary data showing some patients unable to achieve viral response achieved a histologic improvement. There was a slight increase in adverse events for patients receiving pegylated interferon with increases in neutropenia and hyperglycemia, but there was no evidence of a negative effect on HIV infection measured by increases in HIV viral load and decreases in CD4 percentage. The rate of discontinuation (12%) so far in the study is similar to that seen in the registrational studies for patients with HCV alone. He admitted that in the real world as opposed to the controlled setting in which this study is being conducted discontinuation may be a larger issue. But this underscores the need to provide adequate support services to coinfected patients because the data shows they can achieve a viral response.
In summary Thomas said good virologic and perhaps histologic responses can be achieved particularly with pegylated interferon+RBV in coinfected patients. And this can be achieved with the same sorts of adverse events as seen in other studies.
Thomas commented on the important areas for future research. There is almost no area of coinfection that doesnıt need additional research. We need to understand the rate of fibrosis progression for a given individual, so we can advise patients. There is greater uncertainty about this in coinfected patients than in patients with HCV alone. This is because although studies show accelerated progression in HIV we donıt have an understanding of how much more quickly it can progress or at what pace it progresses in HIV. We need more research into the outcomes from treatment and we need to study the optimal duration of therapy. Perhaps with additional treatment responses can be improved. We need to study the benefits of maintenance therapy, and the use of liver transplantation. Very importantly, we need to figure out how to extend access to treatment to communities of patients that are currently not even being evaluated.
In summary, Thomas said treatment should be available to coinfected patients and treatment decisions should be made as in HCV alone based on the individual situation.
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