Beneficial Treatment for Early-Stage Hepatitis C and HIV Co-Infection

Shortened treatments have shown promise in the early stages of hepatitis C (HCV), with a study on the 4-week glecaprevir/pibrentasvir (G/P) regimen presented at the Conference on Retroviruses and Opportunistic Infections (CROI), highlights a promising strategy for HCV elimination, particularly in HIV co-infected populations.

From November 2019 to January 2023, the study enrolled 45 participants predominantly male (98%), with a diverse racial background (51% White, 27% Black, 31% Hispanic/Latino), and a median age of 36 years (ranging from 22 to 65) from the US and Brazil. Of these, 27% reported a history of injecting drug use, 84% were diagnosed with their first HCV infection, and 51%were living with HIV, The median time from HCV diagnosis to study enrollment was 31 days (IQR: 15-49), with participants exhibiting a median baseline HCV RNA level of 5.3 log IU/mL (IQR: 3.3-6.0), predominantly genotype 1 (71%), and a median ALT level of 146 U/L (ranging from 22-3866).

The phase 2 study explored the efficacy and safety of a once-daily oral regimen of G/P 300 mg/120 mg for 4 weeks in adults with early-stage HCV. Eligibility for early-stage HCV included a significant new increase in ALT levels (either ≥5x the upper limit of normal (ULN) or >250 U/L if a normal ALT was documented in the year prior, or ≥10x ULN or >500 U/L if no prior ALT or an abnormal ALT was recorded) or detection of HCV RNA after a previously negative antibody test (indicating a first infection) or HCV RNA test (indicating reinfection) within the 24 weeks leading up to study participation.

The study achieved a sustained virologic response (SVR12) 12 weeks after treatment in 38 out of 45 participants (84%), with a confidence interval (CI) of 74%-91%. Excluding a participant lost to follow-up, the SVR12 rate increases to 86% (CI: 76%-93%). SVR12 rates were 83% (CI: 66%-92%) among participants with HIV and 86% (CI: 70%-94%) in those without HIV.

There were no serious adverse events linked to the treatment observed. Among the six participants who encountered a recurrence of viremia by or before the 12-week post-treatment mark (SVR12), the median initial HCV RNA level was notably high at 6.3 log IU/mL (IQR: 5.8-7.1), yet self-reported adherence to the pill regimen was considered good. All 4 individuals who received a subsequent course of treatment with alternative regimens successfully achieved SVR12. The trial's primary aim was to evaluate the SVR12, which is the absence of detectable HCV RNA 12 weeks after completing treatment, to surpass the 80% success rate according to the 90% Wilson CI. For those not meeting the criteria for SVR12, a second opportunity for treatment was made available.

The study shows potential for simplified treatment protocols, improving adherence and accessibility. Future research, focusing on long-term data, is needed to confirm the long-term durability and safety of this approach, aiming to solidify advancements in HCV treatment.

Reference

Kim A, Kang M, Umbleja T, et. al. A Phase II Trial of 4 Weeks of Glecaprevir/Pibrentasvir for Early Hepatitis C Virus: ACTG A5380. Poster #969 presented at CROI 2024. March 3-6, 2023. Denver, CO.