Once-daily glecaprevir coformulated with pibrentasvir may be a highly efficacious and well-tolerated treatment for patients with hepatitis C virus (HCV)/HIV-1 coinfection with or without cirrhosis, according to a study recently published in Clinical Infectious Diseases.1
In this phase 3 study (ClinicalTrials.gov identifier: NCT02738138), the efficacy and safety of glecaprevir/pibrentasvir was evaluated in patients with chronic HCV genotype 1 through 6 and HIV-1 coinfection, including patients with compensated cirrhosis. From May to September of 2016, 153 patients coinfected with HCV/HIV from 9 countries were enrolled in the study. Participants were age ≥18 years and had body mass index ≥18 kg/m2. Compensated cirrhosis was defined by liver biopsy, transient elastography, or serum biomarkers and diagnosed in 16 patients. Patients were either HCV treatment naive or experienced and either antiretroviral therapy naive or on a stable antiretroviral therapy regimen for at least 8 weeks. No patients with HCV genotype 5 were enrolled.
Coformulated glecaprevir/pibrentasvir (300 mg/120 mg) was given orally as 3 100-mg/40-mg tablets taken once daily with food for either 8 (patients without cirrhosis) or 12 (patients with cirrhosis) weeks. HCV RNA plasma was collected and the level was quantified at screening, at day 1, and at weeks 1, 2, 4, 8, and 12, if applicable. The primary efficacy end point was the proportion of total patients with sustained virologic response (SVR) HCV RNA <15 IU/mL 12 weeks after the last day of treatment (SVR12).
Participants treated with once-daily glecaprevir/pibrentasvir achieved an overall 98% SVR12 rate with no relapses regardless of cirrhosis status. Patients without cirrhosis achieved a 99% SVR12 rate after 8 weeks with no virologic failures. One patient with cirrhosis who was HCV treatment naive experienced breakthrough. The low virologic failure rate (1/153; <1%) suggests that SVR12 achievement was not affected by high baseline viral load, presence of baseline polymorphisms, cirrhosis status, or other baseline factors.
Consistent with previous observations, this study showed a favorable safety and drug-drug interaction profile for glecaprevir/pibrentasvir, suggesting the regimen can be administered with minimal on-treatment monitoring. The safety profile of glecaprevir/pibrentasvir was similar in all patients regardless of treatment duration. The most common adverse effects were fatigue and nausea. Although no patient use of tenofovir disoproxil fumarate has been associated with onset or worsening of renal impairment, these effects may be exacerbated by co-administration with certain concomitant medications (HIV-1 protease inhibitors).2,3 In the current study, 87 (57%) patients were taking tenofovir disoproxil fumarate and none experienced worsening of renal function.
Overall, glecaprevir/pibrentasvir treatment yielded similarly high SVR rates as those reported in patients with HCV monoinfection. Study authors concluded that, “these results support the indication of glecaprevir/pibrentasvir as the first 8-week pangenotypic treatment option for HCV/HIV-1 coinfected patients without cirrhosis.”
Disclosure: This clinical trial was funded by AbbVie Inc.
- Rockstroh JK, Lacombe K, Trinh R, et al. Efficacy and safety of glecaprevir/pibrentasvir in patients co-infected with hepatitis C virus and human immunodeficiency virus-1: the EXPEDITION-2 study [published online March 16, 2018]. Clin Infect Dis. doi: 10.1093/cid/ciy220
- Cooper RD, Wiebe N, Smith N, Keiser P, Naicker S, Tonelli M. Systematic review and meta-analysis: renal safety of tenofovir disoproxil fumarate in HIV-infected patients. Clin Infect Dis. 2010;51(5):496-505.
- Goicoechea M, Liu S, Best B, et al. Greater tenofovir-associated renal function decline with protease inhibitor-based versus nonnucleoside reverse-transcriptase inhibitor-based therapy. J Infect Dis. 2008;197(1):102-108.