Spontaneous hepatitis C clearance rare in gay and bisexual men with HIV

Immediate treatment after recent diagnosis recommended in preference to waiting for spontaneous clearance
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Fewer than one in eight gay or bisexual men with HIV spontaneously cleared a recent infection with hepatitis C, a large European study has found. The study investigators say that if hepatitis C virus levels don’t decline within a month of diagnosis in gay or bisexual men with ongoing risk behaviour, direct-acting antiviral treatment should be offered – and in some cases, doctors should not wait, but should offer treatment upon diagnosis.

The findings, published in the journal Clinical Infectious Diseases, come from the PROBE-C study, an observational cohort study of recent hepatitis infections in people with HIV in western Europe. The study was designed to evaluate the rate of spontaneous clearance of hepatitis C in people with HIV and responses to treatment for hepatitis C initiated during acute infection.

Spontaneous clearance of hepatitis C has been observed in between 25% and 50% of people without HIV and is more common in women. In people with HIV, cohort studies have reported spontaneous clearance rates between 5% and 20%.



A drug that acts against a virus or viruses.

direct-acting antiviral (DAA)

Modern drugs for the treatment of hepatitis C, which work directly against the hepatitis C virus. They stop the virus from reproducing by blocking certain steps in its lifecycle.

acute infection

The very first few weeks of infection, until the body has created antibodies against the infection. During acute HIV infection, HIV is highly infectious because the virus is multiplying at a very rapid rate. The symptoms of acute HIV infection can include fever, rash, chills, headache, fatigue, nausea, diarrhoea, sore throat, night sweats, appetite loss, mouth ulcers, swollen lymph nodes, muscle and joint aches – all of them symptoms of an acute inflammation (immune reaction).

ribonucleic acid (RNA)

The chemical structure that carries genetic instructions for protein synthesis. Although DNA is the primary genetic material of cells, RNA is the genetic material for some viruses like HIV.


pegylated interferon

Pegylated interferon, also known as peginterferon, is a chemically modified form of the standard interferon, sometimes used to treat hepatitis B and C. The difference between interferon and peginterferon is the PEG, which stands for a molecule called polyethylene glycol. The PEG does nothing to fight the virus. But by attaching it to the interferon (which does fight the virus), the interferon will stay in the blood much longer. 

Determining how often spontaneous clearance happens and when it is no longer likely to happen could enable doctors to decide when to offer direct-acting antiviral therapy to people with recent infection. Treating acute infection could limit the sexual transmission of hepatitis C among gay and bisexual men, whereas waiting for spontaneous clearance – which may be a low-probability event – could permit further hepatitis C transmission.

The study recruited people with HIV with a positive hepatitis C RNA test within the past year and a negative hepatitis C antibody or RNA test 12 months prior to the positive hepatitis C RNA test.

People were also eligible to join the study if they had a negative hepatitis C antibody test and a history of normal liver enzymes followed by a persistent increase in ALT and a positive hepatitis C virus (HCV) antibody result.

The study enrolled 464 participants between 2007 and 2017; all but seven were men. Almost all participants were exposed to hepatitis C through sex between men. Sharing of injecting equipment was a risk factor for hepatitis C transmission in only 0.7% of those recruited to the study. Fifty-one participants had been reinfected with hepatitis C.

Ninety-one percent were taking antiretroviral treatment, 90% had a suppressed viral load and the median CD4 count of participants was 574.

Spontaneous clearance occurred in 55 participants (12%), a median of 13 weeks after the first positive HCV-RNA test, with three-quarters of all clearances occurring by 18 weeks. The absence of an HCV RNA decline of at least two logs, four weeks after diagnosis, was associated with a very high probability of persistent, or chronic, infection.

The study investigators say that this finding leaves no doubt as to when treatment should start in people who have been diagnosed with recent infection: as reflected in European AIDS Clinical Society guidelines, direct-acting antiviral treatment should start four weeks after diagnosis if HCV viral load has not fallen by two logs.

Seventy-nine percent of participants subsequently initiated hepatitis C treatment in the 144-week follow-up period. Participants started pegylated interferon treatment a median of 14 weeks after diagnosis, compared to 44 weeks after diagnosis for people initiating direct-acting antiviral treatment. The delay in initiating direct-acting antiviral treatment was due to reimbursement and licensing restrictions on the use of direct-acting antivirals during acute infection. Only 14% of people diagnosed after the introduction of direct-acting antivirals in 2017 were able to initiate treatment within 24 weeks, compared to 75% in 2007.

The cure rate in people receiving direct-acting antivirals was 93%; in people receiving pegylated interferon, it was 73%.

The study investigators say that their findings reinforce recommendations that direct-acting antiviral treatment should start as soon as recent hepatitis C infection is diagnosed, to limit onward transmission. Although the long-term benefit of early hepatitis C treatment is unclear, the investigators say that the consequence of not treating is clear in people with HIV: faster progression of liver progression and earlier development of liver cirrhosis and other complications, compared to people without HIV.