• Manford Penn posted an update 2 days, 16 hours ago

    In the VALENCE study, HIV-uninfected persons with HCV genotype 3 infection were treated with sofosbuvir plus weight-based ribavirin for 24 weeks, leading to SVR in 85% of treatment-naïve and treatment experienced patients [94]. In the PHOTON-1 study, the same regimen sofosbuvir and weight-based ribavirin was evaluated in 223 HIV-infected patients with genotype 1, 2 or 3 infections [35]. The treatment duration was 24 weeks for treatment-naïve patients with genotype 1 (n = 114) and for, treatment-experienced patients with HCV genotype 2 (n = 24) or 3 (n = 17). Sixty-eight treatment-naive patients with HCV genotype 2 (n = 26) or 3 (n = 41) were treated for 12 weeks. Based on the lack of relevant drug interactions in healthy volunteer studies, patients received antiretroviral therapy containing efavirenz, atazanavir/ritonavir, darunavir/ritonavir, raltegravir see more and rilpivirine. The majority of patients enrolled were male (81%–91%) and taking antiretroviral therapy (90%–98%); the median CD4 cell count was high (585–658 cells/mm3) and few patients had cirrhosis (4%–24%). Among treatment-naïve patients, the SVR rates varied by genotype and were similar to the SVR observed in HIV-uninfected patients: genotype 1, 76%; genotype 2; 92%; genotype 3, 67%. Among treatment-experienced patients, the SVR rate was 92% for patients with genotype 2 and 88% for patients with genotype 3. The majority of virologic failures were patients with on-treatment response followed by viral relapse after stopping treatment; resistance to sofosbuvir was not reported in patients with virologic failure. Treatment discontinuation due to adverse effects was observed in 3% of patients treated for 24 weeks; the most commonly reported adverse events were fatigue, insomnia and headache. No adverse impact on HIV disease or its treatment with antiretroviral therapy was detected. However, hyperbilirubinemia was seen in two-thirds of patients taking atazanavir/ritonavir due to ribavirin-induced haemolysis, coupled with atazanavir-induced inhibition of human UDP-glucuronosyltransferase 1A (UGT1A). While this was not associated with clinical harm, four patients switched from atazanavir to darunavir. Anaemia (haemoglobin <10 grams/dl) occurred in 17% of patients treated for 24 weeks; no patients took epoetin alfa or had blood transfusions. Taken together, the findings of the clinical trials of sofosbuvir/ribavirin found similar rates of sustained virologic response in HCV genotype 1, 2, and 3 infected persons with and with HIV coinfection (Fig. 1). The fixed-dose combination of sofosbuvir/ledipasvir (one tablet daily) has been studied with and without ribavirin in HIV-uninfected persons with genotype 1 infection. In the ION-1 and ION-3 studies, treatment-naïve, HIV-uninfected patients were treated with sofosbuvir/ledipasvir with or without ribavirin for 8, 12 or 24 weeks [53] and [55].