Ledipasvir and Sofosbuvir (Harvoini®) for Hepatitis C Virus (HCV) in Patients Coinfected with Human Immunodeficiency Virus One (HIV-1)

Julie Murphy, Mercer University College of Pharmacy

According to the Centers for Disease Control and Prevention, nearly 25% of patients infected with HIV are also infected with HCV and this number increases in those who are intravenous drug users. It is also stated that HCV is the leading cause of chronic liver disease in the United States and that its progression is increased in cases of HIV coinfection.1

Title: Ledipasvir and Sofosbuvir for HCV in Patients Coinfected with HIV-12
Design Multicenter, single-group, open-label study; N= 335
Objective To evaluate 12 weeks of treatment with ledipasvir–sofosbuvir in patients with HIV-1 who were coinfected with HCV genotype 1 or 4, including patients with compensated cirrhosis and those in whom previous treatment with an HCV regimen containing peginterferon, an HCV protease inhibitor, or direct-acting antiviral drugs including sofosbuvir had failed
Study Groups N/A
Methods Patients were enrolled from 60 sites in the United States, Puerto Rico, Canada, and New Zealand. All patients received HIV-1 antiretroviral treatment per protocol for eight weeks before screening and they had to show evidence of HIV-1 suppression. All patients then received a daily dose of ledipasvir/sofosbuvir 90/400 mg for 12 weeks.
Duration March 2014 to September 2014
Primary Outcome Measure The rate of sustained virologic response, which was defined as the absence of quantifiable HCV RNA in serum (<25 IU per milliliter) at 12 weeks after the end of therapy
Baseline Characteristics The mean patient age was 52 years with 82% of patients being male. The majority of patients were Caucasian (61%) and African American (34%). HCV genotypes included type 1a (75%), type 1b (23%), and type 4 (2%). The median HCV ribonucleic acid (RNA) interquartile range (IQR) was 6.9 log10 IU/mL and the median CD4+ cell count IQR was 628 cells/µL. The majority of patients had IL28B genotype CT (55%) with CC (24%) and TT (21%) also reported. Cirrhosis was seen in 20% of patients and 45% of patients had no previous HCV treatment. The antiviral regimens included Truvada® (emtricitabine and tenofovir disoproxil fumarate) plus Sustiva® (efavirenz) (48%), Isentress® (raltegravir) (44%), or Edurant® (rilpivirine) (9%).
Results At 12 weeks after the end of therapy, 96% of patients had sustained virologic response.
Adverse Events Common: Headache (25%), fatigue (21%), diarrhea (11%), nausea (10%), arthralgia (7%), upper respiratory tract infection (5%), vomiting (4%), muscle spasms (3%), constipation (3%), dysgeusia (2%), and sinusitis (2%)
Serious: Hepatocellular carcinoma and portal-vein thrombosis (1%); arthralgia, azotemia, clostridium difficile colitis, cough, diarrhea, ileus, bacterial peritonitis, respiratory tract infection, sepsis, and substance abuse (<1%)
Percentage that Discontinued due to Adverse Events: Zero
Study Author Conclusions Ledipasvir and sofosbuvir for 12 weeks provided high rates of sustained virologic response in patients coinfected with HIV-1 and HCV genotype 1 or 4.

The two incidences of HCV breakthrough were associated with suspected patient noncompliance. Out of the ten episodes of virologic relapse, all ten patients were African American, seven of them possessed the IL28B TT allele, and eight patients received the efavirenz antiviral regimen. Further analysis found that the African American race and the TT allele factors were significantly associated with treatment failure with the African American race being the only independent factor.2

Limitations to this study included the use of restricted antiretroviral regimens which is not consistent with standard practices. It was an open-label study which increases risk of bias and it lacked a control group. Patients who were taking Norvir® (ritonavir)-boosted HIV-1 protease inhibitors or Tybost® (cobicistat)-boosted elvitegravir plus tenofovir disoproxil fumarate were excluded due to known increased risk of adverse events.2


  1. HIV/AIDS and Viral Hepatitis. Centers for Disease Control and Prevention. cdc.gov/hepatitis/populations/hiv.htm. Accessed August 27, 2015.
  2. Naggie S, Cooper C, Saag M, et al. Ledipasvir and Sofosbuvir for HCV in Patients Coinfected with HIV-1. N Engl J Med. 2015;

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