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HCV/HIV Coinfection at IAS
Management of HCV/HIV Coinfection: New Data From IAS 2015

Released: September 08, 2015

Expiration: September 06, 2016

Jürgen Rockstroh
Jürgen Rockstroh, MD
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During the oral hepatitis session at the recent International AIDS Society (IAS) conference in Vancouver, multiple studies were presented on the efficacy and safety of all-oral, direct-acting antiviral (DAA) combinations in individuals with HCV/HIV coinfection, including in the setting of cirrhosis and previous HCV treatment experience.

DAA Combination Clinical Trials
The DAA combinations studied included the once-daily, fixed-dose combination ledipasvir/sofosbuvir in 335 patients with genotype 1 or 4 HCV infection in the phase III ION-4 study; ombitasvir/paritaprevir/ritonavir plus dasabuvir and ribavirin, which requires twice-daily dosing, in 62 patients with genotype 1 HCV infection in the phase II/III TURQUOISE-I study; and grazoprevir/elbasvir, an investigational once-daily, fixed-dose combination, in 218 patients with genotype 1, 4, or 6 HCV infection in the phase III C-EDGE study. For each of these combinations, SVR rates were between 96% and 97% overall. Moreover, the rate of study discontinuations due to drug-related adverse events was close to 0%, underlining the dramatically improved safety and tolerability of all-oral DAA regimens over previous therapies, particularly when they are ribavirin free. Clearly, these high SVR rates have prompted guideline panels to no longer distinguish between HCV-monoinfected and HCV/HIV-coinfected subjects, with updated guidance from AASLD/IDSA and EASL now stating that the indication and choice of HCV regimen should no longer differ between these 2 groups. Considering recent history in which patients with HCV/HIV coinfection were less likely to receive treatment because of the often required longer treatment durations with added toxicity and lower overall cure rates, this development is a tremendous success. It is noteworthy, however, that due to a higher risk for hepatic decompensation in coinfected patients—even those receiving fully suppressive HIV therapy—there remains a need to prioritize patients with HCV/HIV coinfection for HCV treatment over HCV-monoinfected individuals. This recommendation is emphasized accordingly in treatment guidelines.

Overall, these new data have increased my confidence in treating even the more challenging patients with HCV/HIV coinfection with cirrhosis and previous treatment failure, as results from real-life cohorts demonstrate excellent cure rates with all-oral DAA therapy in this particular patient group.

Real-World Data of DAAs in HCV/HIV Coinfection
Critical voices have raised the question whether the high cure rates observed in coinfected individuals in clinical trials can be reproduced in real-life patient settings. This is an extremely relevant issue, as in many countries, HCV treatment is reserved for patients with advanced fibrosis (stage 3 or 4), a patient population sometimes underrepresented in clinical trials. I was, therefore, reassured to hear the first results from the French multicenter compassionate use program assessing the efficacy of daclatasvir and sofosbuvir with or without ribavirin in a patient population with HCV genotypes 1, 3, or 4 and HIV coinfection where 76% of study participants were cirrhotic and 85% treatment experienced. The overall SVR rate was 90% in the strict sensitivity analyses, comprising 159 patients with available HCV RNA assessments at posttreatment Week 12 or with detectable HCV RNA at posttreatment Week 4 but without posttreatment Week 12 data (the latter of whom were considered virologic failures). Clearly, this outcome further demonstrates that high SVR rates for patients with HCV/HIV coinfection have become a reality even in real-world settings among patients with advanced disease.

HCV Reinfection Among Coinfected Individuals
One interesting finding that appears relatively unique to HCV/HIV coinfection is that, in many studies—including C-EDGE—a small number of patients can be identified who experience a new rise in HCV RNA after achieving end-of-treatment response but prior to SVR assessment. In the C-EDGE study, phylogenetic analyses revealed that this increase in HCV RNA was likely due to reinfection rather than relapse. In this setting, HCV reinfection is likely to result from persistent high-risk behavior among HIV-seropositive men who have sex with men (MSM). Indeed, HCV reinfection has been described to occur in up to 25% of MSM with HCV/HIV coinfection within 2 years of receiving HCV treatment. These data strongly call for behavioral interventions, as curing HCV with DAAs alone will not be sufficient. Larger prevention and awareness campaigns targeting this specific patient population are needed.

The Impact of Fibrosis Regression on Survival
Finally, interesting data were presented from a retrospective analysis evaluating the impact of SVR and liver fibrosis regression on clinical outcomes in 133 patients with HCV/HIV coinfection who received treatment with peginterferon/ribavirin. During 7 years of follow-up, fibrosis regression was more predictive than SVR of improved overall survival and liver disease–related survival. These data indicate that the overall benefit of therapy may not include survival prolongation if treatment occurs in very late stages of disease where the reversibility of cirrhosis is limited. Moreover, it suggests that treatment in liver disease stages where fibrosis regression is still possible is crucial for improving survival. These data further support the argument for earlier HCV therapy across the board.

Your thoughts?
I’d like to hear from you. Based on new data from IAS 2015, would you agree that all HCV/HIV-coinfected patients should receive treatment regardless of fibrosis stage? What strategies do you employ for preventing HCV reinfection among your high-risk patients? I encourage readers to post their thoughts in the comments section below.

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When treating with DAA HCV combination therapy, are the SVR rates obtained in your clinic similar to those reported in clinical trials?
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