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Predictive Value of Early Virological Response (12 Weeks) to Pegylated Interferon plus Ribavirin in HIV-HCV Co-infected Patients
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This study was presented by Spanish researchers at ICAAC in September 2002 and again at Retrovirus 2003. In this small study of 89 HCV/HIV coinfected patients, no patients who did not achieve a 2 log reduction in viral load by week 12 was able to achieve an undetectable HCV-RNA at the end of treatment (6 or 12 months therapy with interferon plus ribavirin). The negative predictive value was 100%. There have been a number of studies in HCV mono-infected showing that the week 12 cutoff was reasonable. Very few patients who did not achieve a 2-log viral load reduction by week 12 went on to achieve a sustained viral response. However, this Spanish study in coinfection is small and needs to be confirmed with more research. This research is too preliminary, as other small research studies suggest coinfected patients may take longer to mount a response to therapyperhaps due to an impaired immune response. Following are the details of the study.
HCV-related liver disease is a growing cause of morbidity/mortality among HIV co-infected patients (pts). Treatment of chronic hepatitis C offers now cure to 60% of HIV- pts. Response rates seem to be lower in HIV+ pts, but side effects may be more frequent. Therefore, the recognition of early predictors of lack of treatment response may allow discontinuing anti-HCV
therapy when no benefit is expected to be obtained. Recent guidelines have pointed out that reductions in HCV-RNA > 2 logs at 12 wks of anti-HCV
therapy have a negative predictive value (NPV) of 97%. Therefore, it's been generally recognized that if an HCV mono-infected patient has not had a 2 log reduction in viral load by week 12 on pegylated interferon plus ribavirin it may be appropriate to discontinue therapy. Studies show the possibility of achieving a sustained response is very low. The difficulty in tolerating the medications is so great that it's not worth this difficulty if the possibility for achieving a sustained viral response is so low. There is one exception. If the patient has more advanced liver disease, stage 3 or 4 from biopsy results, you should consider continuing maintenance therapy. Studies show that continued therapy, usually half dose of interferon, can slow disease progression. So continuing on maintenance therapy may slow disease progression to further liver damage and serious complications.
Preliminary reports have shown that HCV-RNA clearance under treatment may be slower in HIV+s. Therefore discontinuing at week 12 may not give a patient adequate opportunity to reduce viral load.
The Spanish investigators analyzed 89 HIV-HCV co-infected patients who completed a course of anti-HCV combination therapy. Pegylated interferon (IFN) was administered to 63 and regular IFN to the remaining 26 patients, always using standard doses. All received a fixed dose of RBV (400 mg bid). HCV genotypes were distributed as follows: 1-4 (62%) and 2-3 (38%). Treatment was provided for 6 months (months) in genotypes 2-3 and for 12 months in genotypes 1-4.
Overall, sustained virological response (SVR) occurred in 29 patients. End-of-treatment response with further relapse was seen in 15. The remaining 45 were non-responders.
A drop in HCV-RNA > 2 logs was seen in 38 (43%) and 52 (58%) of pts at 4 and 12 weeks, respectively. Of those subjects, only 18 (48%) and 29 (56%), respectively, reached SVR.
In contrast, SVR occurred in 11 (38%) and 0 pts who did not show a > 2 log drop in HCV-RNA at wks 4 and 12, respectively. Thus, the NPV was 100% at wk 12. There were no significant differences between HCV genotypes, baseline HCV-RNA, and use of either pegylated or regular IFN. In patients with HCV 2-3, a high rate of relapse in early responders was noticed, suggesting that extending treatment beyond 6 months might have provided a higher SVR rate in them.
The study authors concluded that the use of an early time-decision point at 12 weeks to identify which subjects will not benefit from continuing anti-HCV treatment is valid for HIV+ pts. However, a delayed clearance of HCV-RNA in early responders with HIV might account for a higher relapse rate when treatment is stopped prematurely (e.g., 6 months in genotypes 2-3). (edit note: using their own theory just mentioned of a delayed clearance in HIV-infected patients, I maintain that it is premature, until well confirmed with additional research, to conclude that the 12 week cutoff point is reliable in coinfected patients.
Mayte Perez-Olmeda et al. Hosp Carlos III, Madrid, Spain
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