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Selected Presentations from CROI 2018
Low Spontaneous HCV Clearance in Big European HCV/HIV Cohort
25th Conference on Retroviruses and Opportunistic Infections (CROI), March 4-7, 2018, Boston

Mark Mascolini

Only about 1 in 10 HCV/HIV-coinfected Europeans spontaneously clear HCV after acute infection, according to a 464-person analysis [1]. PROBE-C investigators believe the finding supports early consideration of direct-acting antiviral (DAA) therapy before newly infected people transmit HCV to partners. Christoph Boesecke (Bonn University Hospital) and colleagues titled their study, "Fueling the epidemic: Low rates of spontaneous clearance of acute HCV infection.” [17% % (51/300) were reinfected]

“Which patients will clear spontaneously and which are the ones I should refer to for early treatment and not waste any more time & money” said Christoph Boesecke in his talk.

The researchers noted that several clinical trials show comparable HCV cure rates (sustained virologic response, SVR) with DAA therapy for acute HCV coinfection and chronic HCV. Cohort and modeling data indicate that acute HCV incidence drops when clinicians use DAAs to treat acute HCV. Yet no DAA has an indication for acute HCV infection.

For these reasons, the rese
archers determined rates of spontaneous clearance of acute HCV in a large European HCV/HIV cohort, PROBE-C [2]. Cohort members live in 9 European countries and are at last 18 years old. They have documented current or past acute HCV infection with detectable HCV RNA for an estimated duration of 52 weeks or less at diagnosis. No one has non-HCV acute liver disease.

From 2007 through 2017, PROBE-C identified 464 acute HCV episodes in HIV-positive people with at least 12 months of follow-up. No one started immediate anti-HCV therapy. The group had a median age of 41 years (interquartile range [IQR] 40 to 42), and 98% were men. Transmission risk was gay sex in 98.8%, heterosexual sex in 0.5%, and drug injecting in 0.7%. Median CD4 count stood at 574 (IQR 547 to 604), and 90.8% of cohort members had an HIV load below 200 copies. Median HCV RNA measured 682,646 (IQR 518,000 to 1,149,828). While 78.5% of participants had HCV genotype 1, 18.6% had genotype 4.

HCV load dropped at least 100-fold at week 4 in 13.6% of PROBE-C members. Only 11.9% (55 of 464) spontaneously cleared HCV, while the rest had persistent viremia. Overall 245 of 324 treated people (75.6%) achieved SVR. Fifty-one of 300 treated people with follow-up (17%) got reinfected, indicating ongoing risk behavior after SVR.

Comparing people who had spontaneous clearance with the persistent-viremia group, the researchers found little difference in median age (42 and 41), proportion of men who have sex with men (97.7% and 98.9%), median CD4 count (544 and 580), proportion with an HIV load below 200 (94.1% and 90.4%), or median HCV load (677,481 and 687,811). Compared with chronically infected people, those with spontaneous clearance had a lower proportion taking antiretroviral therapy (83.6% versus 92.6%, P = 0.036) and a much higher proportion with more than a 100-fold drop in HCV RNA by week 4 (96.4% versus 2.5%, P < 0.001).

Multivariate analysis identified only one factor independently associated with spontaneous HCV
clearance: more than a 100-fold 4-week drop in HCV load boosted chances 1115-fold (95% confidence interval 225.5 to 5515.3, P < 0.001). Factors not independently associated were age, gender, HCV load, HIV load, taking antiretrovirals, median alanine aminotransferase, and HCV genotype.

The PROBE-C team argued that
"DAA drug labels as well as clinical guidelines need to be amended to allow usage of DAAs during the acute phase of HCV infection in a high-risk population." The European AIDS Clinical Society (EACS) just revised its guidelines to support early DAA therapy for acute HCV infection in high-risk people.

1. Boesecke C, Muller Martinez E, Nelson M, et al. Fueling the epidemic: low rates of spontaneous clearance of acute HCV coinfection. 25th Conference on Retroviruses and Opportunistic Infections (CROI). March 4-7, 2018. Boston. Abstract 129.
2. ClinicalTrials.gov. The natural history and treatment of acute hepatitis C virus (HCV) in HIV-positive individuals (PROBE-C). ClinicalTrials.gov identifier NCT01289652. https://clinicaltrials.gov/ct2/show/NCT01289652