IAS: Hepatitis C clusters reveal international transmission among HIV-positive gay men

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Clusters of acute hepatitis C in the United Kingdom and elsewhere in Europe provide further evidence that sexual transmission is occurring internationally among HIV-positive gay men, researchers reported Tuesday at the Fourth International AIDS Society Conference on HIV Treatment, Pathogenesis and Prevention.

Six years ago, sexual transmission of HCV among gay men was almost completely under the radar, with many physicians believing that it was a very rare occurrence.

Beginning in the early 2000s, however, doctors in large cities in the UK and Europe (including the Netherlands, Germany and France) started seeing outbreaks of acute hepatitis C, mostly among HIV-positive men who have sex with men. There have now been nearly 400 such cases reported in London and Brighton alone, and similar outbreaks have since been observed in Australia and the United States.

Glossary

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).

gene

A unit of heredity, that determines a specific feature of the shape of a living organism. This genetic element is a sequence of DNA (or RNA, for viruses), located in a very specific place (locus) of a chromosome.

pathogenesis

The origin and step-by-step development of disease.

exclusion criteria

Defines who cannot take part in a research study. Eligibility criteria may include disease type and stage, other medical conditions, previous treatment history, age, and gender. For example, many trials exclude women who are pregnant, to avoid any possible danger to a baby, or people who are taking a drug that might interact with the treatment being studied.

control group

A group of participants in a trial who receive standard treatment, or no treatment at all, rather than the experimental treatment which is being tested. Also known as a control arm.

As aidsmap has previously reported, these acute HCV infections appear to be sexually transmitted, and have been linked to risk factors including unprotected anal sex, fisting, multiple partners, group sex practices, concurrent sexually transmitted infections, and non-injection recreational drug use.

Given the mobility of gay men between European cities like London, Amsterdam and Berlin, an international group of researchers decided to investigate patterns of HCV transmission in northern Europe.

Mark Danta from the UCL Institute of Hepatology in London and colleagues recruited 190 HIV-positive men who had been diagnosed with acute HCV infection between 2000 and 2006. Of these, 107 were from the UK, 51 were from the Netherlands, 24 were from Germany, and eight were from France.

All were men who have sex with men, with an average age of about 38 years. Between two-thirds and three-quarters of the men in the various countries were taking HAART, and the mean CD4 cell count ranged from about 400 to about 600 cells/mm3.

Using blood samples, the researchers compared parts of the NS5B sequence of the HCV genome and constructed phylogenetic trees to better understand the linkages between these cases.

Phylogenetic testing compares viral gene sequences with a control group in order to determine the likelihood that samples from the study group are related. Although phylogenetic testing is not considered a reliable way to prove that one individual has infected another, it can provide suggestive information about clusters of infection.

Half the men were infected with HCV genotype 1a, followed by genotype 4d (23%), with the remainder distributed between genotypes 3a (7%), 1b (5%), and 2 (2%). Genotype information was not available for 24 men (13%), who were excluded from further analysis. Compared with the overall distribution of HCV genotypes in northern Europe, the proportion with genotype 4 was unusually high.

The phylogenetic analysis revealed ten clusters that together accounted for 88% of all the HCV isolates, ranging in size from three to 36 individuals. Seven of the ten clusters contained sequences from more than one country, and four contained isolates from more than two countries. One of the two genotype 4d clusters -- which comprised 31 men and was the second largest cluster overall -- included samples from all four countries.

The researchers concluded that this phylogenetic analysis reveals a large HCV transmission network among HIV-positive gay men in Europe, and that travel between countries presumably plays an important role in transmission. Further, they noted, international mixing increased with larger cluster size, indicating rapid spread of regional outbreaks to neighbouring countries.

They recommended that national public health agencies should implement targeted prevention strategies, including HCV screening for high-risk HIV-positive men who have sex with men, to reduce the spread of hepatitis C in this population.

During the discussion following the presentation, Greg Dore from Sydney said that researchers were now analysing gene sequences from gay men with acute hepatitis C in Australia. Danta urged American researchers to collaboration as well, in an effort to learn whether outbreaks in these countries may be linked to those in Europe.

References

Danta M et al. Evidence of international transmission of HCV in pan-European study of HIV-positive men who have sex with men (MSM). Fourth International AIDS Society Conference on HIV Treatment and Pathogenesis, Sydney, abstract TUAB201, 2007.