Virologic Response Following Combined Ledipasvir and Sofosbuvir Administration in Patients With HCV Genotype 1 and HIV Co-infection

May Le, PharmD candidate 2015

Mercer University College of Pharmacy

About one-third of HCV infected patients will develop cirrhosis within around 20 years.  The progression rate is even faster in HIV co-infected patients despite antiretroviral therapy treatment, which can cause drug induced liver injury.  Patients with HIV infection often will be screened for HCV infection.  Due to poor sustained virologic response rate, peginterferon with ribavirin is no longer the main treatment therapy for HCV infection.  The new class of HCV direct acting antiviral, which includes sofosbuvir and ledipasvir, is an alternative.1

A recent published study looked at virologic response of sofosbuvir and ledipasvir in HIV co-infected patients.2

Title:  Virologic Response Following Combined Ledipasvir and Sofosbuvir Administration in Patients With HCV Genotype 1 and HIV Co-infection
Design Open-label, uncontrolled, single-center, pilot study; 50 participants
Objective To evaluate the rates of sustained virologic response (SVR) and adverse events of ledipasvir and sofosbuvir therapy in untreated hepatitis C virus (HCV) genotype 1 patients co-infected with human immunodeficiency virus (HIV)
Study Groups Everyone: Fixed-dose combination of ledipasvir (90 mg) and sofosbuvir (400 mg) daily for 12 weeks

Antiretroviral therapy group: (n= 37)

No antiretroviral therapy group: (n= 13)

Methods Patients were given the combination therapy.  Plasma HCV RNA levels measured with the real-time HCV assay (Abbott). Measured HCV RNA levels on days 0, 1, 3, 5, 7, and 10 and weeks 2, 3, 4, 8, 12, 14, 16, 20, and 24
Duration June 2013 to September 2014
Primary Outcome Measure Proportion of patients with SVR, defined as plasma HCV ribonucleic acid (RNA) level < 12 international units (IU) per milliliter, 12 weeks after finished therapy
Baseline Characteristics Antiretroviral therapy group: median age 58, men 30, white 4, black 32, Hispanic 1, fibrosis score 0 (22%), fibrosis score 1 (51%), fibrosis score 2 (5%), fibrosis score 3 (22%), median HCV RNA 6, mean HCV RNA 6, CD4 cells < 200 (3%), CD4 cells 200- 350 (22%), CD4 cells > 350 (76%)

No antiretroviral therapy group: median age 59, men 7, white 3, black 10, Hispanic 0, fibrosis score 0 (15%), fibrosis score 1 (46%), fibrosis score 2 (0%), fibrosis score 3 (38%), median HCV RNA 6.1, mean HCV RNA 5.8, CD4 cells < 200 (0%), CD4 cells 200- 350 (8%), CD4 cells > 350 (92%)

Results Antiretroviral therapy group with SRV: 36 (97%)

No antiretroviral therapy group with SRV: 13 (100%)

Confidence Interval: 95%

No p value provided for primary outcome results

Adverse Events Common Adverse Events: Nasal congestion (16%), myalgia (14%), headache (10%), fatigue (10%), diarrhea (8%), nausea (6%), constipation (6%), urinary tract infection (6%)
Serious Adverse Events: Pneumonia (2%)
Percentage that Discontinued due to Adverse Events: None
Study Author Conclusions Administration of an oral combination of ledipasvir and sofosbuvir for 12 weeks was associated with high rates of SVR after treatment completion. Larger studies that also include patients with cirrhosis and lower CD4 T-cell counts are required to understand if the results of this study generalize to all patients co-infected with HCV and HIV.

This study showed promising results with sofosbuvir and ledipasvir.  A benefit is that the duration of therapy is shorter than ribavirin therapy.  They are appropriate options for physicians who don’t want to use interferon or ribavirin.  However, larger clinical trials with controlled and double blinded design against main therapy and trials with patient population excluded in this study are needed.

References:

  1. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use ofantiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Available at http://aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf. Accessed 3/25/2015.
  1. Osinusi A, Townsend K, Kohli A, et al. Virologic response following combined ledipasvir and sofosbuvir administration in patients with HCV genotype 1 and HIV co-infection. JAMA. 2015;313(12):1232-9.
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