Successful treatment of sexually acquired acute HCV reinfection with ledipasvir/sofosbuvir in a HIV-infected patient

Introduction

In the last decade, hepatitis C has emerged as a sexually transmitted infection among HIV-infected men who have sex with men (MSM),^1,2 with high transmission rates ³ and the spread of an ongoing acute hepatitis C (AHC) epidemic among this population.^4–8 HIV-positive MSM who had been successfully treated for their primary HCV infection showed alarmingly high reinfection rates of 9.6–15.2 per 100 person-years, with a two-year cumulative incidence of 25–33%^9,10 and some subjects developing multiple consecutive episodes. ¹¹ In this setting, early treatment of acute HCV infection and reinfection episodes in individuals with low chance of spontaneous clearance ¹² may curtail onward transmission of HCV. The availability of highly efficacious and well-tolerated all-oral direct-acting antiviral (DAA) therapies for chronic hepatitis C (CHC) raises the question of whether they should also be used in the acute phase of HCV infection. ¹³ To date, none of the currently available DAAs has been licensed for AHC, and pegylated interferon (PEG-IFN)-α plus ribavirin remains the gold standard of treatment. ¹⁴

Case

In 2011, a 59-year-old HIV-infected homosexual man with no history of injection drug use received a 24-week course of PEG-IFN-α and ribavirin for acute HCV genotype 2 infection, achieving a sustained virological response (SVR). In March 2015, while he was on stable antiretroviral therapy with tenofovir/emtricitabine/rilpivirine, his blood tests showed CD4⁺ T-cell count of 544 cells/mm³, plasma HIV-1 RNA <37 copies/ml, and a severe increase in alanine aminotransferase (ALT) level (996 IU/L). HCV RNA level was greater than 1 × 10⁷IU/ml and genotyping showed genotype-1 a, while other causes of hepatitis were excluded. Thus, acute HCV reinfection was diagnosed. As regards the transmission route, the patient reported unprotected anal sex with multiple partners in the last three months. FibroScan showed a liver stiffness of 8.6 kPa suggestive of METAVIR score F2; abdominal ultrasonography was unrevealing. HCV RNA and ALT levels were monitored 12 weeks for spontaneous resolution; in June 2015, they were 3.5 × 10⁶IU/ml and 212 U/l, respectively. The patient was concerned about transmission risk and keen to initiate therapy, but refused a new course of PEG-IFN and ribavirin, previously poorly tolerated; moreover, he displayed an unfavorable interleukin-28B non-C/C genotype. Since he could not be treated with IFN-free regimens through the National Health System, he had access to DAAs privately. Ledipasvir (LDV)/sofosbuvir (SOF) for 12 weeks led to a dramatic decrease in the HCV RNA level followed by an SVR at post-treatment weeks 12 and 24 and ALT normalization (Figure 1). No adverse event occurred during treatment. Written informed consent was provided by the patient for this report.

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Figure 1.

HCV RNA and ALT levels prior, during, and after antiviral treatment with ledipasvir/sofosbuvir (LDV/SOF).

Discussion

To our knowledge, this is the first report of an HIV-positive patient with sexually acquired acute HCV reinfection successfully treated with LDV/SOF combination. Treatment of AHC with PEG-IFN-α and ribavirin for 24–48 weeks in HIV-infected patients resulted in overall SVR rates of 53–91%^12,15,16; the addition of first-generation DAAs telaprevir or boceprevir in acute HCV genotype-1 infection yielded SVR rates of 84–86% after 12 weeks of treatment, but at the cost of frequent toxic effects^17,18; IFN-free regimens with second-generation DAAs endowed with greater activity and tolerability now promise to further improve SVR rates after 12 (or less) weeks of treatment.^19,20 With new DAAs still only being licensed for chronic HCV infection and advanced liver fibrosis in most resource-rich and almost all resource-limited countries, HIV-coinfected patients with AHC currently have two options: (1) treatment with PEG-IFN-α and ribavirin for 24–48 weeks or (2) no treatment until the development of chronic phase and, in most cases, advanced liver disease, when they may have access to IFN-free DAA regimens. However, the first option seems disadvantageous in terms of SVR rates, treatment duration and side effects compared with all-oral DAA regimens in CHC; the second option seems even more detrimental, due to the ongoing AHC epidemic and to the greater risk for HCV persistence and faster progression to cirrhosis in HIV-coinfected compared to HCV-monoinfected patients. ²¹ In the ION-4 trial, LDV/SOF for 12 weeks provided a 96% SVR rate in 335 patients chronically coinfected with HIV/HCV genotypes 1 and 4. ²² Although there are very limited data on LDV/SOF in AHC patients with HIV coinfection, ²⁰ similar, or even superior, SVR rates and tolerability profile are expected. Furthermore, there is evidence for the possible efficacy of four-week to six-week courses of LDV/SOF or other DAA combination therapy in both non-HIV and HIV-positive patients with acute HCV infection, which makes the treatment of AHC cost-saving as compared to treatment of CHC.^23–25

Our case suggests some important considerations. First, there is urgent need for HCV prevention campaigns among HIV-positive MSM. Second, considering the risk of reinfection in HIV-positive MSM who cleared HCV, surveillance through regular HCV RNA testing should be carried out. Third, the treatment of patients in the acute phase of the disease is of key importance to control the current epidemic of AHC among HIV-positive MSM. Finally, the efficacy and safety of LDV/SOF in our patient showed the tremendous potential of all-oral DAA regimens in AHC, which makes it unethical to restrict them to patients with advanced CHC. Studies are required to define the role of DAAs in the treatment of AHC.