Background: Historically HIV co-infection was considered a negative predictor of HCV response to treatment with interferon/ribavirin (IFN/RBV). For sofosbuvir-based regimens, HIV/HCV patients have achieved similar sustained virologic response (SVR) rates as HCV monoinfected patients. We evaluated the safety and efficacy of the IFN-free, RBV-free, single tablet regimen of ledipasvir/sofosbuvir (LDV/SOF) in HCV genotype 1 or 4 patients co-infected with HIV-1 in the Phase 3 ION-4 study.
Methods: HCV treatment naïve and experienced HIV co-infected patients on stable, approved antiretroviral (ARV) regimens were enrolled and received LDV/SOF (90mg/400mg) once daily for 12 weeks. Patients with compensated cirrhosis were eligible. Permitted concomitant ARVs included tenofovir and emtricitabine (TDF+FTC) with raltegravir (RAL), efavirenz (EFV) or rilpivirine (RPV). Safety evaluations included adverse event (AE) and standard laboratory parameter monitoring in addition to enhanced renal toxicity monitoring, CD4 count and HIV-1 RNA levels. The primary efficacy endpoint was SVR12.
Results: 335 patients with GT1a (75%), GT1b (23%) and GT4 (2%) were enrolled; 82% were male, 61% were white, mean age was 52 (range 26-72), mean baseline HCV RNA was 6.7 log10 IU/mL (range 4.1-7.8), median baseline CD4 count was 662 cells/uL (Q1, Q3=469, 823), 20% had cirrhosis, 24% were IL28B CC genotype and 55% had not responded to prior HCV treatment. Patients were taking EFV (48%) or RAL (44%) or RPV (9%). The table shows SVR12 by ARV regimen. Overall, the SVR12 rate was 96% (320/335); 2 patients had on-treatment virologic failure likely due to non-compliance and 10 had virologic relapse after discontinuing treatment. SVR12 was similar among non-cirrhotic (96%) and cirrhotic (94%) patients and also among treatment naïve (94%) and treatment experienced (97%) patients. No patient had confirmed HIV virologic rebound (HIV-1 RNA≥400 copies/mL). No patients discontinued study drug due to an AE. AEs occurring in ≥10% of patients were headache (25%), fatigue (21%) and diarrhea (11%). No significant lab abnormalities were observed.
Conclusions: The IFN-free, RBV-free, single tablet regimen of LDV/SOF administered once daily for 12 weeks is highly effective and well tolerated in treatment-naïve and experienced, genotype 1 or 4 HCV-infected patients with HIV-1 co-infection, including those with cirrhosis.
| Virologic Response | TDF+FTC+EFV ⇥⇥⇥(N=160) |
TDF+FTC+RAL ⇥⇥⇥(N=146) |
TDF+FTC+RPV ⇥⇥⇥(N=29) |
Overall ⇥⇥⇥(N=335) |
| SVR12, n (%) | 151 (94) | 141 (97) | 28 (97) | 320 (96) |
| On-Treatment Failure, n (%) | 1 (<1) | 0 | 1 (3) | 2 (<1) |
| Relapse, n (%) | 8 (5) | 2 (1) | 0 | 10 (3) |
| Other, n (%) | 0 | 3 (2) | 0 | 3 (<1) |