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STD 2016: HCV Infection and Reinfection Among Men Who Have Sex with Men

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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. Routine HCV screening at sexual health clinics can help detect more HCV infections among gay men, and prevention measures are needed to address the risk of HCV reinfection after spontaneous clearance or a cure, researchers concluded in recent related journal articles.

Starting in the early 2000s, researchers in the U.K. 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 U.S.

The 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, rectal secretions, and feces. 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 T-cell counts.

Michigan HCV Cluster

At the STD Prevention Conference Jenny Gubler from 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 cases 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 1 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, gonorrhea, chlamydia, and lymphogranuloma venereum.

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 U.S.

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

HCV Screening in Amsterdam

As described in the September edition of Sexually Transmitted Diseases, Martijn van Rooijen from the Public Health Service of Amsterdam and colleagues evaluated whether routine HCV screening of HIV-positive men at a sexual health clinic would result in more and earlier diagnoses.

U.S. and European hepatitis C guidelines recommend that HIV-positive MSM who have "unprotected" -- implying condomless -- sex should be tested annually for HCV, but this is often not widely implemented.

Amsterdam was among the first cities to report outbreaks of sexually transmitted HCV among MSM, and in 2007 a municipal STI clinic introduced routine HCV antibody screening for gay and bi men who were HIV-positive or of unknown HIV status. All such clients were tested at their first clinic visit, and thereafter only those who initially tested HCV-negative were retested.

The researchers found that 112 out of 1724 HIV-positive clients (6.4%) and 3 of 446 unknown-status clients (0.7%) tested HCV antibody-positive at their first visit. During follow-up another 32 HIV-positive men and no unknown-status men became newly infected with HCV (incidence rate 2.35 per 100 person years). In addition, 4 of 34 HIV-positive men (11.8%) who were notified by their sexual partners that they'd been exposed to HCV tested HCV-positive.

Only 78 of the 163 HIV-positive men who tested HCV antibody-positive reported a known history of hepatitis C. The researchers then requested HCV diagnosis data from the remaining patients' HIV clinic to compare dates; this was available for 54 men. Of these, 51.9% were first diagnosed with HCV at the STI clinic.

"The introduction of routine anti-HCV testing at the STI outpatient clinic resulted in additional and earlier HCV detection among HIV-positive MSM," the study authors concluded. "Testing should be continued among HIV-positive MSM, at least for those not (yet) under the care of an HIV clinic and those notified of HCV by their sexual partner."

HCV Reinfection

Finally, as 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 behavior, including people who inject drugs and men who have sex with men. One meta-analysis of 61 studies found that the 5-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 8 centers in Austria, France, Germany, and the U.K. 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 (2 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, 5 men had a third reinfection and 1 man 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 2 years after clearance. Reinfection rates varied considerably across centers, 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 5 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 behavior in a potentially specific high-risk group, who require urgent targeting for prevention measures related to risk behaviors," the authors added. They recommended that HIV-positive gay men who have been infected once with HCV should be tested for reinfection every 3 to 6 months, and those who have been reinfected should be retested every 3 months.

9/27/16

References

J Gubler, S Johnson, and J Coyle. Cluster of Sexually Transmitted Hepatits C Virus Among the MSM Population in Southeast Michigan. 2016 STD Conference. Atlanta, September 20-23, 2016. Abstract 3F4.

M van Rooijen, T Heijman, N de Vrieze, M Prins, et al. Earlier Detection of Hepatitis C Virus Infection Through Routine Hepatitis C Virus Antibody Screening of Human Immunodeficiency Virus-Positive Men Who Have Sex With Men Attending A Sexually Transmitted Infection Outpatient Clinic: A Longitudinal Study. Sexually Transmitted Diseases 43(9):560-565. September 2016.

P Ingiliz, TC Martin, A Rodger, et al. HCV reinfection incidence and spontaneous clearance rates in HIV-positive men who have sex with men in Western Europe. Journal of Hepatology. September 17, 2016 (online ahead of print).