HCV antibody testing may miss recent infections in gay men living with HIV

Nucleic acid testing should be used to diagnose acute hepatitis C virus (HCV) infections in gay men living with HIV, Dutch research published in the online edition of Clinical Infectious Diseases shows. HCV antibodies only developed a median of 74 days after infection with the virus. Over half of people who had a successful response to HCV therapy lost their HCV antibodies during follow-up. However, there was a high rate of re-infection, and these could be reliably diagnosed using antibody testing.

“Screening for acute HCV is…preferably performed using nucleic acid testing instead of anti-HCV testing,” write the authors.

Epidemics of sexually transmitted HCV have been observed among HIV-positive gay and other men who have sex with men (MSM) in several European and US cities. Routine HIV care for people at risk of HCV should include regular HCV screens, including testing for HCV RNA and HCV antibody testing.

But the utility of antibody testing – especially for the diagnosis of acute infections – is open to question. People with HCV mono-infection typically develop antibodies within 30-70 days of infection, but there have been reports of a delayed antibody response in people with HIV co-infection.

Investigators in Amsterdam therefore designed a study to examine the HCV antibody dynamics in gay men living with HIV with an estimated date of HCV infection. Their aims were to determine time to emergence of antibodies following infection; antibody response to spontaneous clearance or successful therapy; and antibody activity following HCV re-infection.

The study sample comprised 63 MSM. Most received care after 2009 and retrospective testing of stored blood samples gave a firm date of primary infection with HCV. Follow-up lasted four years.

All participants in the study developed HCV antibodies. The median time between infection and the emergence of antibodies was 74 days. Just over half (59%) had antibodies within three months of infection, 73% within four months and 98% at twelve months.

“Among 17/63 subjects (27%) in our study, no anti-HCV antibodies were detected four months after the estimated date of HCV infection,” comment the researchers. They believe this shows the importance of using HCV RNA testing to detect recent infections. But they also note that the median time to the emergence of antibodies – 74 days – was comparable to that observed in some research involving people with HCV mono-infection.

Overall, 36 participants cleared their infection, 31 after HCV therapy. A decrease, but not complete loss of HCV antibodies, was observed in people with spontaneous clearance. The cumulative incidence of loss of antibodies was 37% within three years of their initial appearance, and 51% within three years of a successful treatment response. Lower peak HCV viral load was associated with disappearance of antibodies.

A total of 21 re-infections were observed in 18 people who cleared the virus. Peak HCV antibody levels were significantly higher following re-infection compared to primary infection (p = 0.014). Disturbances in liver function were less pronounced following re-infection compared to primary infection (median ALT, 66 vs. 119 u/l), suggesting that monitoring liver function may not pick-up all re-infections.

“Our main findings were that (1) the seroconversion window in this population was comparable to the seroconversion window reported among HIV-uninfected subjects, (2) seroreversion was very common following successful antiviral treatment, and (3) after an initial decrease in anti-HCV levels following SVR, levels increased following reinfection to levels reached during primary infection or higher,” comment the authors.

They conclude, “monitoring antibody dynamics following SVR could thus be a useful and inexpensive alternative or additional tool for evaluation and diagnosis of HCV reinfection in the HIV-infected MSM population.”

But Dr Thomas Reiberger of the HIV and Liver Study Group, Medical University of Vienna, author of an editorial that accompanies the study emphasises that acute HCV infections could be missed if only antibody testing was used. Early detection is important for prevention of onward transmission and also for provision of treatment - HCV is more likely to be cleared by interferon-based treatment during acute infection. He concludes that the study’s findings support “broader use of sensitive quantitative PCR-based HCV-RNA testing in this high-risk population.”