December 17, 2001
The authors presented their finding of an increased risk for pancreatitis in patients taking ddI plus D4T and INF plus RBV. The data comes from a retrospective analysis of records which had been examined for clinical pancreatitis -- diagnosis was based upon increased levels of lipase, and other tests documenting pancreatitis. There was a total of 25 patients, 10 of whom were diagnosed with "pancreatitis." Those diagnosed with pancreatitis were assigned to either of two groups. One group had chemical pancreatitis -- five patients (two fold). The other group of five patients had clinical pancreatitis. The 25 patients were all stable in their HIV therapy, with a CD4 over 400, and the pancreatitis episode resolved when the RBV, IFN or both, were decreased or d/c. The conclusion is that RBV and both ddI and d4T increased the risk of pancreatitis to 40 percent. The median time for toxicity was 84 days from the start of the hepatitis C therapy. The poster also presented the possible mechanism behind pancreatitis in HIV/HCV co-infected patients which was thought to be increased intracellular levels of the drugs caused by RBV interaction.
It is important to recognize the adverse events that may be caused by therapy, but this study makes statements that cannot be concluded from the data presented. First, this is a retrospective study and thus it is difficult to make assumptions backwards regarding adverse events. The diagnoses of "chemical pancreatitis" reported in the retrospective analysis are not valid. If these cases are thrown out, then only 5 of the 25 cases had clinical pancreatitis, a percentage of about 10% -- the same as the sum of the increased risk for pancreatitis seen for both RBV and IFN. Second, the number of people looked at in the study is too small. Third, there is no specific data regarding what were the measures taken, the time for clinical resolution, or chemical response. Fourth, the risk for pancreatitis in both RBV and IFN is known, but rarely seen. Also, there has been no significant clinical study of the interaction between the HIV and the HCV therapy. It needs to be pointed out that the combination of d4T and ddI is not commonly used, and even when used, this problem is seen in less than 40 percent of the patients taking these drugs. This risk may be increased in the setting of HIV/HCV co-infection, but this study does not answer how important the risk is. This question will be resolved as soon as the data is available from the global study in co-infection, (Pegasys and RBV). The study will have prospective data on complications and PK levels of HIV drugs used in combination with RBV.
I have another concern with this study that is based on questions I have had from patients about the side effects of HIV/HCV treatment. These reports of complications, valid or not, will have an impact on the decisions made by infectious disease specialists regarding the safety of HCV therapy. Unfortunately, these doctors may become so concerned that they are reluctant to treat, when the reality is that the majority of co-infected patients tolerate therapy as well or better than those who are infected with only hepatitis. We need careful follow-up of patients, not excessive caution that will result in fewer patients treated for HCV.
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