Ledipasvir/sofosbuvir (LDV/SOF) fixed-dose combination is highly effective and safe for genotype 1 HCV-infected patients with HIV co-infection. Of the 335 HCV/HIV coinfected patients enrolled in the ION-4 Phase 3 study, 3% relapsed (n=10) after 12 weeks of LDV/SOF treatment. These patients were eligible for a retreatment substudy that evaluated the efficacy and safety of LDV/SOF (90 mg/400 mg) plus weight-based RBV for 24 weeks.
Eligible patients were enrolled within 60 days from the time of confirmed virologic failure. NS5A and NS5B resistance associated variants (RAVs) were evaluated by deep sequencing prior to retreatment and at the time of virologic failure post-retreatment. The primary endpoint was SVR12.
Nine of 10 patients were enrolled and completed treatment. All patients were black, IL28B non-CC, HIV suppressed on ARV regimens with a median baseline CD4 count of 785 cells/uL (Q1, Q3 = 404, 971). The mean age was 57 years (range 35-65) and most were male (n=7), without cirrhosis (n=7), and had genotype 1a infection (n=7). The mean baseline HCV RNA was 6.2 log10 IU/mL (range 4.4-7.1). HIV ARV regimens included tenofovir+emtricitabine (TDF+FTC) with either efavirenz (n=7) or raltegravir (n=2). Prior to retreatment, 2 patients had no NS5A RAVs and 7 patients had high-level NS5A RAVs detected (see Table). The SOF-specific NS5B RAV S282T was not detected in any patients; 1 patient had L159F. Overall SVR12 rate was 89% (8/9): 1 patient relapsed. There were no treatment-emergent SAEs. Fatigue (n=6), cough (n=4), anemia (n=2) and arthralgia (n=2) were the most common adverse events. No significant lab abnormalities were observed and creatinine clearance was stable on treatment. No patient had confirmed HIV virologic rebound (HIV-1 RNA≥400 copies/mL).
Ledipasvir/sofosbuvir with ribavirin for 24 weeks was well tolerated and demonstrated that successful retreatment is possible in the majority of these genotype 1-infected, NS5A-experienced HCV/HIV co-infected patients.