Hepatitis C infection and reinfection among men who have sex with men need higher priority, US and European studies show

Public health officials in Michigan have identified a cluster of more than 20 cases of apparently sexually transmitted hepatitis C virus (HCV) infection among HIV-positive gay and bisexual men, according to a report at the 2016 STD Conference last week in Atlanta. A recently published related study saw a high rate of HCV reinfection among gay men and concluded that prevention measures are needed to address the risk of HCV recurrence after spontaneous clearance or a cure.

Starting in the early 2000s, researchers in the UK and elsewhere in Europe began reporting clusters of apparently sexually transmitted acute HCV infection among HIV-positive men who have sex with men (MSM); similar outbreaks followed in Australia and the US.

The US Centers for Disease Control and Prevention (CDC) has held that sexual transmission of HCV is rare – at least among monogamous HIV-negative heterosexuals. HCV sexual transmission among gay and bi men is not fully understood. It has traditionally been assumed that HCV is transmitted through sexual activities that involve blood, but the virus has also been detected in semen and in rectal secretions and faeces. A number of risk factors have been implicated – including condomless anal sex, fisting, group sex, use of sex toys, having other sexually transmitted infections (STIs) and non-injected recreational drug use – but these have not been consistent across studies.

Sexually transmitted HCV infection has mostly been seen among HIV-positive gay and bi men, though some cases have also been reported among HIV-negative men – including a few among men on PrEP. It is unclear why HCV sexual transmission is more common among men with HIV, since it can occur in those with well-preserved immune function and high CD4 cell counts.

HCV cluster in Michigan

At the STD Prevention Conference Jenny Gubler of the Michigan Department of Health and Human Services reported findings from an investigation of sexually transmitted HCV among MSM in Detroit.   

In February 2016 an “astute clinician” notified the health department about an increase in acute or recent HCV infections among HIV-positive gay and bi men who did not inject drugs.

The department began an investigation to determine the scope of the outbreak, matching HCV case reports to individuals in its Electronic HIV/AIDS Reporting System. Disease intervention specialists interviewed men and their contacts and recommended testing for HCV antibodies and HCV RNA. 

As of mid-September the department had identified 22 confirmed cases and 11 suspected cases in Detroit and surrounding counties, with around 30 sexual contacts still under investigation. 

All 22 cases involved HIV-positive men. Most were African American and ages ranged from 21 to 48 years. All of the men reported having sex with men, and all but one said they had never injected drugs – the most common risk factor for hepatitis C.

While all are in HIV care, only about half had undetectable HIV viral load. Most also reported a history of other STIs including syphilis, gonorrhoea, chlamydia and lymphogranuloma venereum (LGV).

Many of the identified HCV infections were acute or new seroconversions after a previous negative test, indicating recent infection. Isolates that underwent genotypic testing were found to be genotype 1a, the most common type in the US and Europe.

The investigators said they plan to carry out additional molecular characterisation and patient interviews to learn more about HCV transmission patterns in this community.

HCV reinfection in Europe

In a related study reported in the September 17 online edition of Journal of Hepatology, Patrick Ingiliz and fellow investigators with the NEAT study group did an analysis of HCV reinfection rates among HIV-positive gay and bi men in Europe.

Up to a quarter of people with acute HCV infection – somewhat less if HIV-positive – will naturally clear the infection without treatment, while the remainder develop chronic or long-term infection. HCV usually does not confer full protective immunity and people can be reinfected after spontaneous clearance or successful treatment. However, it appears that spontaneous clearance becomes more likely with subsequent infections, suggesting the immune system may get better at controlling HCV.

HCV reinfection remains a possibility for individuals with ongoing risk behaviour, including people who inject drugs and men who have sex with men. One meta-analysis of 61 studies found that the five-year risk of HCV reinfection among HIV-positive MSM was as high as 15% – higher than in most studies of people who inject drugs, the study authors noted as background.

This retrospective analysis included 606 HIV-positive MSM at eight centres in the UK, Austria, France and Germany within the European AIDS Treatment Network who were followed between May 2002 and June 2014.

Of these, 111 men spontaneously cleared their initial HCV infection (two negative HCV tests at least 24 weeks apart after a positive test), while 494 were cured with pegylated interferon plus ribavirin (SVR12, or undetectable HCV RNA at 12 week post-treatment).

During follow-up 149 participants (24.6%) presented with subsequent HCV reinfection after viral clearance, defined as recurrent detectable HCV RNA after these time points, or within these time frames if the HCV genotype was different. The median CD4 count at the time of reinfection was 533 cells/mm³ and 82% had undetectable HIV viral load. Almost all had elevated alanine aminotransferase (ALT), a marker of liver inflammation.

Of the 70 men who spontaneously cleared HCV a second time or were successfully treated again, 30 (43%) presented with a second reinfection. In addition, five men had a third reinfection and one had a fourth reinfection.

The overall incidence of first HCV reinfection among 552 patients with complete data was 7.3 per 100 person-years (PY), occurring a median of two years after clearance. Reinfection rates varied considerably across centres, ranging from 5.0 per 100 PY in Hamburg to 21.8 per 100 PY in Paris. The incidence of a second reinfection was much higher, at 18.8 per 100 PY.

The researchers noted a trend toward a lower reinfection rate among people who spontaneously cleared HCV compared to those who were cured with treatment, but the difference did not reach statistical significance (4.9 vs 7.8 per 100 PY; p = 0.06).

Looking at outcomes among men who were reinfected, 15.6% spontaneously cleared their first reinfection and 28.6% did so after their second reinfection – possibly indicating increased HCV-specific immune responses. Spontaneous clearance of reinfection was associated with ALT levels >1000 IU/ml and spontaneous clearance of the first HCV infection.

“We found a high reinfection incidence of 7.3/100 PY with an estimate that almost one-third of patients [were] reinfected after five years,” the study authors summarized.

“These numbers highlight the failure of current prevention strategies and the need for specific measures in the HIV-infected MSM population at risk in Europe,” they wrote in their discussion. “As new, well tolerated, but costly HCV treatments have become the standard of care for HCV therapy, there is an urgent need to develop strategies to prevent reinfection at such scale.”

The higher incidence of second reinfection compared to first reinfection “indicates a maintained risk behaviour in a potentially specific high-risk group, who require urgent targeting for prevention measures related to risk behaviours,” the authors added. They recommended that HIV-positive gay men who have been infected once with HCV should be tested for reinfection every three to six months, and those who have been reinfected should be retested every three months.