To the Editor:
Since the introduction of highly active antiretroviral therapy, hepatitis C virus (HCV) infection has emerged as a major cause of morbidity and mortality in patients with HIV infection.1
Although treatment with pegylated interferon (pegIFN) and ribavirin has significantly improved the therapeutic outcome of chronic HCV hepatitis, 30% to 50% of such patients do not achieve a sustained virologic response (SVR), and lower response rates are recorded in HCV/HIV-coinfected patients for several reasons, including a poorer treatment tolerance.2 Recent studies evidenced that IFN α-2b is highly effective in patients with acute HCV hepatitis (ACH), with rates of SVR higher than those achievable with pegIFN and ribavirin in chronic C hepatitis.3 There are no data on the effectiveness of pegIFN in HIV-positive patients with ACH.
Based on the favorable results obtained in the treatment of acute HCV infection in non-HIV-infected subjects,4 we administered pegIFN α-2b on a open-label basis to 4 consecutive HIV-infected patients who developed ACH.
Diagnosis of ACH was made with positive HCV RNA and elevated serum alanine aminotransferase (ALT) levels with documented seroconversion for anti-HCV antibodies or the presence of a known risk factor in the preceding 6 months.
Patients received supervised treatment with pegIFN α-2b at a dosage ranging between 1.1 and 1.5 μg/kg once weekly for 12 weeks. ALT level, CD4 cell count, HCV RNA, and HIV RNA measurements were made at baseline and at weeks 1, 2, 3, 4, 8, 12, 24, and 36. The HCV RNA measurements were analyzed by a quantitative branched DNA assay (bDNA, version 3.0 Assay, Versant, Bayer, Tarritown, NY), with a lower detection limit of 3.2 × 103 copies/mL and by a qualitative reverse transcriptase polymerase chain reaction (RT-PCR; Cobas Amplicor HCV test version 2.0, Roche, Branchburg, NJ) with a lower detection limit of 125 copies/mL. The primary endpoint was the SVR, defined as a negative RT-PCR result 24 weeks after the end of treatment.
Two patients were women. The median age was 32.5 years (range, 23-62 years), and the median time from HIV infection was 30 months (range, 4-96 months). HCV genotype 1 was found in 2 patients and genotype 2 in the other 2 patients. All patients were naive for antiretroviral therapy. Risk factors for HCV transmission were intravenous drug use (50%) and sexual exposure (50%). Only one patient had constitutional symptoms attributable to acute HCV infection. At baseline, the median HCV RNA level was 7.5 × 106 copies/mL (range, 3.2 × 103-39.5 × 106); the median HIV RNA level was 5 × 104 copies/mL (range, 2 × 104-26 × 105) and the median CD4 cell count was 431/mm3 (range, 404-567). Treatment was given within 120 days (range, 30-120) since the peak level of ALT.
All patients completed the supervised 12-week course of pegIFN without significant side effects or dose reduction. As shown in Table 1, the SVR was achieved in 3 patients (75%); the patient in whom treatment failed had a negative bDNA at week 8 and negative RT-PCR results only at week 12 but subsequently relapsed. It is noteworthy that all 3 responders had negative RT-PCR findings as early as week 4, with ALT normalization at week 3. The patient who did not respond had the highest baseline HCV RNA load, the oldest age, and had received the lowest IFN dose (1.1 μg/kg).
At the 1st week, a mean decrease of HIV RNA of 0.6 log10 was recorded, with no further changes until the end of therapy. At week 12 the HIV RNA increased and returned to values comparable to baseline. No significant changes in CD4 cell count were observed throughout the study period.
The treatment outcome of acute HCV infection has been repeatedly shown to be far more favorable than that achievable in chronic HCV hepatitis. According to the data reported here, the same seems to apply to HIV/HCV-coinfected subjects. A short treatment course with pegIFN provided an SVR of 75%, was well tolerated, and did not interfere with any significant HIV-related parameter. Furthermore, as also seen in HCV-monoinfected patients with acute infection, the therapeutic response was not influenced by the HCV genotype.4
Although no definite conclusion can be drawn from this small study, our findings suggest that the treatment of ACH in HIV-infected patients deserves to be further explored to better define the time of intervention and the most appropriate dosage and treatment duration with pegIFN.
As opposed to what is usually seen in intravenous drug users, in subjects at risk for sexual exposure transmission of HCV infection may take place after HIV infection. Although intravenous drug use remains the major risk factor for HCV infection, an increased sexual transmission of HCV has recently been reported, especially in the presence of other sexually cotransmitted diseases (eg, syphilis).5 Currently, sexual activity ranks as the 2nd risk factor for HCV infection in patients with acute hepatitis, suggesting that sexual transmission may contribute significantly to the total burden of HCV infection.6 Because a sizeable proportion of patients who acquired HIV through the sexual route are still free of HCV infection, attention should be paid to the serologic screening for acute C hepatitis in any subject with persistent risk factors, or when ALT levels increase during antiretroviral treatment. Should these results be further validated in larger clinical studies, the early detection and treatment of HCV infection might provide a unique opportunity for reducing its relevant morbidity and mortality burden in subjects with HIV infection.
Sabrina Audagnotto, MD, DTM&H
Francesco Giuseppe De Rosa, MD
Olivia Bargiacchi, MD
Silvia Garazzino, MD
Lorenzo Veronese, MD
Giuseppe Cariti, MD
Giovanni Di Perri, MD, PhD, DTM&H
Department of Infectious Diseases University of Turin Turin, Italy
1. Soriano V, Sulkowsky MS, Bergin C, et al. Care of patients with chronic hepatitis C and HIV co-infection: recommendations from the HIV-HCV International Panel. AIDS
2. Perez-Olmeda M, Nunez M, Romero M, et al. Pegylated IFN-alpha2b plus ribavirin as therapy for chronic hepatitis C in HIV infected patients. AIDS
3. Jaeckel E, Cornberg M, Wedemeyer H, et al. Treatment of acute hepatitis C with interferon alpha-2b. N Engl J Med
4. De Rosa FG, Bargiacchi O, Audagnotto S, et al. HCV-RNA dynamics during the first month of treatment with pegylated interferon in patients with acute C hepatitis [V-1150]. Paper presented at: 44th Interscience Conference on Antimicrobial Agents and Chemotherapy; October 30-November 2, 2004; Washington, DC.
5. Ghosn J, Pierre-Francois S, Thibault V, et al. Acute hepatitis C in HIV-infected men who have sex with men. HIV Med
6. Terrault NA. Sexual activity as a risk factor for hepatitis C. Hepatology