Ledipasvir/Sofosbuvir for 8 Weeks to Treat Acute Hepatitis C Virus Infections in Men With Human Immunodeficiency Virus Infections: Sofosbuvir-Containing Regimens Without Interferon for Treatment of Acute HCV in HIV-1 Infected Individuals

Abstract

Background: Current guidelines for the management of hepatitis C virus (HCV) infections provide varying recommendations for the optimal treatment of acute HCV infections. There are limited data from small cohort studies to provide guidance on the best approach to treatment of this important patient population.

Methods: Sofosbuvir-Containing Regimens Without Interferon for Treatment of Acute HCV in HIV-1 Infected Individuals is an open-label, 2-cohort, Phase 1 clinical trial in which the second cohort assessed the safety and efficacy of 8 weeks of ledipasvir/sofosbuvir for the treatment of acute HCV infections in participants with chronic human immunodeficiency virus (HIV)-1 infections. This final analysis of the second cohort had a planned accrual of 27 participants, based on non-inferiority criteria, compared to the study-defined, historical, sustained virologic response (SVR) of 60% with pegylated-interferon/ribavirin.

Results: We enrolled 27 men (9 Hispanic; 11 White, non-Hispanic; 5 Black, non-Hispanic; 2 Asian or Pacific Islander; median age 46 years). Most (96%) had HCV genotype-1 infection and 59% had the favorable interleukin 28B CC genotype. The median baseline HCV RNA load was 6.17 log10 IU/mL (interquartile range 4.51 - 6.55). All participants (100%) achieved the primary outcome of a sustained virologic response 12 weeks after the date of the last dose of study treatment (90% confidence interval 90-100%), achieving non-inferiority versus the 60% historic benchmark. No treatment discontinuations occurred.

Conclusions: This multicenter clinical trial, investigating 8 weeks of ledipasvir/sofosbuvir for acute HCV infections in men with HIV infections, reports a 100% SVR. This study provides the rationale for larger studies of shortened courses of direct-acting antiviral therapies in persons with HIV infections, including those with high baseline HCV RNA loads.

Clinical trials registration: NCT02128217.

Keywords: direct-acting antivirals; early infection; human immunodeficiency virus; interferon-free; men who have sex with men.

Figure 1.

Sofosbuvir-Containing Regimens Without Interferon for Treatment of Acute HCV in HIV-1 Infected Individuals cohort 2 flow diagram.

Figure 2.

Time to achieve an undetectable HCV RNA load, according to baseline HCV viral load. The horizontal axis represents the study week and the vertical axis represents HCV RNA load log₁₀ IU/mL. The crosses indicate the last time each participant had a detectable HCV RNA load; the open circles show the times of the first undetectable HCV RNA loads; the lines represent the range of possible times when a participant may have become undetectable. Abbreviations: <LLOQ TND, less than lower limit of quantification target not detected; HCV, hepatitis C virus.

Figure 3.

Serum creatinine change from baseline during study treatment and post-treatment follow-up periods among participants on TDF-containing antiretroviral regimens. The horizontal axis represents the study weeks and the vertical axis represents the changes in serum creatinine levels from baseline. The dark gray boxes represent the interquartile ranges for changes in serum creatinine for participants on pharmacologically-boosted TDF-containing antiretroviral regimens, and the light gray boxes represent the interquartile ranges for changes in serum creatinine for participants on all other TDF-containing antiretroviral regimens. The hashed vertical line represents the end of dosing and start of follow-up. Abbreviations: COBI, cobicistat; PI, protease inhibitor; TDF, tenofovir disoproxil fumarate.

Figure 4.

Serum creatinine clearance change from baseline during study treatment and post-treatment follow-up periods among participants on TDF-containing antiretroviral regimens. The horizontal axis represents the study weeks and the vertical axis represents changes in serum creatinine clearance from baseline. The dark gray boxes represent the interquartile ranges for changes in serum creatinine clearance for participants on pharmacologically-boosted TDF-containing antiretroviral regimens, and the light gray boxes represent the interquartile ranges for changes in serum creatinine clearance for participants on all other TDF-containing antiretroviral regimens. The hashed vertical line represents the end of dosing and start of follow-up. Abbreviations: COBI, cobicistat; PI, protease inhibitor; TDF, tenofovir disoproxil fumarate.