Little Overlap of Sexually Transmitted HCV between U.S. and Europe

	SUMMARY: A phylogenetic analysis of more 200 hepatitis C virus (HCV) strains from HIV positive gay and bisexual men revealed extensive clustering of related viruses within U.S. cities, but little overlap between the East and West coasts, or between the U.S. and Europe or Australia, according to findings presented at the at the 18th Conference on Retroviruses and Opportunistic Infection (CROI 2011) this month in Boston.

By Liz Highleyman

For the past decade researchers have reported outbreaks of apparently sexually transmitted acute hepatitis C among HIV positive men who have sex with men (MSM), first in the U.K., then in large cities in Europe, Australia, and the U.S.

Although details vary from study to study, these acute HCV infections have been linked to unprotected anal intercourse, fisting, multiple sex partners, group sex, use of sex toys, nasal drug use, and presence of other sexually transmitted diseases; coinfected men typically do not report injection drug use.

Daniel Fierer from Mt. Sinai School of Medicine in New York City and colleagues conducted a genetic analysis to see if cases of acute HCV infection among HIV positive gay/bisexual men in the U.S. are genetically related to the European and Australian cases.

In 2009, Thijs van de Laar and colleagues reported results from a phylogenetic analysis indicating that HCV from coinfected gay and bisexual men in Europe and Australia fell into clusters of related viruses. More than 80% of European HCV strains and about 40% from Australia belonged to 11 clusters, some of which included men from multiple countries. These findings they wrote, "revealed a large international network of HCV transmission among HIV positive MSM."

In the analysis presented at CROI, investigators looked at new HCV infections among HIV positive MSM in 6 U.S. cities. They sequenced a 436 base pair region of the HCV NS5B polymerase gene and constructed phylogenetic trees to show the relationship among U.S. viral strains, and between U.S. strains and those found in Europe and Australia.

Since HCV accumulates mutations as it replicates, viral strains that are closer to one another in a tree are more recently descended from a common ancestor; degree of relationship, therefore, can reveal transmission patterns.

The comparison included 102 HCV sequences from men in the U.S. (77 from New York City, 12 from San Francisco, 9 from Boston, 2 from Philadelphia, and 1 each from Los Angeles and San Diego), as well as 128 men in Europe and Australia. All had hard-to-treat HCV genotype 1.

Results

	About 90% of U.S. HCV strains were genotype 1a and about 10% were genotype 1b.
	None of the U.S. men in this analysis had an unusual genotype 4 HCV strain seen in European men.
	HCV strains could be grouped into 9 clusters, each representing 3 to 10 individuals.
	7 clusters were found among men in New York City.
	More than half the patients fell into at least 1 of these clusters.
	There were 8 pairs (2 person clusters) of homologous, or very similar, viral sequences.
	67% of the U.S. men carried an HCV sequence that was very similar to that found in at least 1 other man, usually from the same city.
	There was extensive clustering within cities, especially New York and San Francisco.
	There was limited clustering, however, between cities in the Northeast U.S.
	There was also limited clustering between East Coast and West Coast cities, although there was a New York/San Diego pair and a New York/San Francisco cluster.
	There was minimal overlap between U.S. HCV sequences and those from Europe or Australia, although 2 San Francisco strains fell into large European clusters.

"Molecular epidemiology shows little overlap between U.S., European, and Australian cities, suggesting largely independent evolution of epidemics, not a network of transmission," the investigators concluded.

"Besides a few strains sweeping across countries, what we have is simultaneous behavior clusters," Fierer said. "We need better prevention efforts."

Investigator affiliations: Mt Sinai School of Medicine, New York, NY; Centers for Disease Control and Prevention, Atlanta, GA; Univ of California San Francisco School of Medicine, San Francisco, CA; Weill Cornell Medical College, New York, NY; Univ of Pennsylvania School of Medicine, Philadelphia, PA; Univ of New South Wales, Sydney, Australia; VU Univ Medical Ctr, Amsterdam, Netherlands.

3/15/11

Reference
D Fierer, Y Khudyakov, B Hare, et al. Molecular Epidemiology of Incident HCV Infection in HIV-infected MSM in the US vs Infections in Europe and Australia. 18th Conference on Retroviruses and Opportunistic Infections (CROI 2011). Boston. February 27-March 2, 2011. Abstract 112.