Report 5 from Dallas, 50th AASLD, Saturday, Nov 7

Below are 2 reports on IL-2 treatment in HCV treatment. And the effects of PI therapy for HIV on HCV fibrosis progression.

Sustained HCV Eradication After IL-2 Therapy in Patients with HCV/HIV Co-Infection
Joerg Schlaak and others from German research group (University of Essen, Essen, Germany; University of Mainz, Mainz, Germany) reported these preliminary data from a small (n=7) study. They said there is increasing evidence that co-infection of hepatitis C with HIV is associated with accelerated progression to liver cirrhosis. With prolonged survival of HIV-patients this will become a major clinical problem especially in countries where these co-infections are very common.

(comments from Jules—several studies suggest that HIV can speed progression of HCV and HIV can speed progression of HCV. These concerns can affect the decision of when to begin HCV treatment in co-infection) 

In patients with more advanced HIV infection therapeutic options are limited and liver transplantation is contra-indicated (questionable). Thus, new therapeutic strategies are needed for patients with co-infection. 7 HIV infected individuals with HCV were treated with IL-2 in a dose of 1-2 MU s.c. All patients received concomitant anti-retroviral therapy. During therapy CD4s, quantitative HIV RNA, quantitative HCV RNA, liver enzymes, as well as clinical and lab parameters were monitored.

Authors said data show that all patients responded to IL-2 with either improvement in CD4 count or liver function tests. During therapy HCV eradication was not observed. In 2 female patients, however, HCV RNA became negative 2 and 4 months, respectively, after cessation of therapy. In both patients, a mild flare of hepatitis was seen before IL-2 therapy was stopped. HCV RNA in serum is negative in these 2 patients for 6 and 11 months, respectively. Authors assumed IL-2 has led to sustained viral eradication in 2 or 7 patients since spontaneous resolution of HCV is raely seen in HIV patients and HIV medications are not supposed to effect HCV replication. They suggested these results are mediated possibly through a modulation of the anti-HCV immune response since it occurred after cessation of IL-2. To me, other factors than IL-2 therapy may have played a role in these 2 clearing HCV. The following study suggests protease inhibitor therapy in HIV may slow liver fibrosis progression and thus HCV progression.

HIV Protease Inhibitor Therapy and Duration of PI Therapy May Be Associated Slower Liver Fibrosis Progression
Christine Katlama and others in French HIV research group reported here in Dallas and also at ICAAC HIV Conference in September that individuals co-infected with HIV and HCV who receive protease inhibitor therapy for HIV can experience decreased liver fibrosis progression rates. What if the 2 patients in German study above were taking protease inhibitors for HIV? The authors here said HCV related liver fibrosis progression is accelerated in HIV infected patients. The objective of their study is to examine the impact of combination anti-retroviral therapy for HIV including a PI on liver fibrosis progression rates.

162 consecutive HCV-HIV coinfected patients (119 male; 36.7 yrs age) were studied. At liver biopsy, HCV duration was 14.4 years, CD4s were 327, and HIV RNA was performed in 79 patients (17,823 copies/ml). 42 patients had self-recorded alcohol consumption (SRAC above 50g/day). At liver biopsy, 49 patients were receiving PI therapy for 12 months. Estimated FPR (fibrosis progression rate) was defined as ratio between fibrosis stage (METAVIR scoring system) and HCV duration. Since the linearity of liver fibrosis progression remains questionable only non-parametric statistical tests were used for univariate and multivariate analysis.

Patients receiving PI therapy had higher duration of HCV infection and lower HIV viral load than patients who had never received PI treatment (17 vs 14 years, p=0.04; 12,154 vs 22,332 copies/ml, p=0.03). Neither CD4 count nor alcohol consumption showed significant difference between the 2 groups. Patients with high FPR (above 2.0 fibrosis units/year; that is, expected time from HCV infection to cirrhosis below 20 years , n=45) included more patients older than 20 years at HCV infection, with a SRAC (alcohol consumption) above 50 g/day, and with a CD4 count below 200, and less patients treated with a PI compared to patients with low FPR (equal to or below 2.0 fibrosis units/year, n=117).

Logistic regression analysis identified 2 independent factors associated with high FPR: CD4 count below 200 (odds ratio=15; p below 0.0001)) and no previous treatment with PI (odds ratio=3.8, p=0.02). The duration of PI therapy is associated with a low FPR in HCV-HIV coinfected patients. The independent association between PI therapy and liver fibrosis progression is not explained by the studied factors, including the CD4 count (I. Poynard T et al Lancet 1997; 825-32). 

Treating HIV infection and co-infection is becoming increasingly complicated, calling moreso for well trained doctors.