Hepatitis C in HIV-positive gay men: Amsterdam, Paris, New York and UK compared

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Several posters at the Sixteenth Conference on Retroviruses and Opportunistic Infections in Montreal examined the rise in sexually transmitted hepatitis C in gay men with HIV, each highlighting different aspects of this new epidemic. Risk behaviour was compared between New York and the UK; researchers documented an apparently separate and long-lasting epidemic of HCV genotype 4 in France (in all other cities, genotype 1 predominated); New York investigators documented rapid progression of liver fibrosis in their patients, and also treatment success rates.

These studies have followed on from an alarming one presented at the International AIDS Conference in Mexico last year, which found that 18% of a group of HIV-positive gay men at a single clinic in Amsterdam had hepatitis C (HCV) – a third of them with recent infection – and that its prevalence was growing rapidly. At the time, Kevin Fenton of the US Centers for Disease Control questioned the limited public health response to the outbreaks of hepatitis C in Europe and called for a greater sense of urgency.

Amsterdam

The Amsterdam study presented at CROI (Van den Berk) looked specifically for acute HCV infection – defined symptomatically as marked rises in liver enzymes or testing positive for HCV. It found 46 cases of acute HCV infection between 2003 and August 2008 in a large cohort of about 1380 gay male HIV-positive patients treated at a single hospital clinic.

It found that although acute cases were not as common as in the other Amsterdam study, they were increasing exponentially. There were two in 2003, one in 2004, nine in 2005, twelve in 2006, six in 2007 and 14 in the first eight months of 2008 (equivalent to a 2008 incidence of 1.5% a year). Fifty-nine per cent of patients, based on previous negative HCV tests, had had HCV infection for less than a year. Three-quarters of patients had genotype 1. None of the patients had classic risk factors such as injecting drug use or medical exposure to infected blood.

France

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).

fibrosis

Thickening and scarring of connective tissue. Often refers to fibrosis of the liver. See also ‘cirrhosis’, which is more severe scarring.

receptive

Receptive anal intercourse refers to the act of being penetrated during anal intercourse. The receptive partner is the ‘bottom’.

equivalence trial

A clinical trial which aims to demonstrate that a new treatment is no better or worse than an existing treatment. While the two drugs may have similar results in terms of virological response, the new drug may have fewer side-effects, be cheaper or have other advantages. 

insertive

Insertive anal intercourse refers to the act of penetration during anal intercourse. The insertive partner is the ‘top’. 

The French researchers (Ghosn) presented the results of a national cohort screen for cases of acute HCV infection. They looked through the records of HIV-positive gay men in 115 clinical settings. They found 94 cases of acute HCV infection, defining it in this case as a positive HCV test within a year of a negative one. Of these 32 had complete medical and lab data and also had their HCV infection gene-sequenced.

The men investigated were aged 40 on average and had had HIV for ten years. Twenty two (62.5%) had undetectable HIV viral loads and over half had a CD4 count over 500.

Twenty out of the 32 patients had an STI diagnosed at the same time as HCV, of which 14 had syphilis; a concomitant STI was one of the largest risk factors for HCV. Other significant risks included unprotected anal sex and either surgery or endoscopy. Only five patients cited fisting, often suspected of spreading HCV, as a risk factor.

The researchers found that 14 out of the 32 had genotype 1a, the most common in most other developed-world epidemics, but that 16 or 50% were of the relatively uncommon genotype 4d. Of the genotype 1 viruses, ten were in three infection clusters of three or four members each, suggesting infection chains or a common source, and all 15 of the genotype 4d viruses were in a single cluster of near-identical viruses, suggesting a large connected network of gay men with HCV. Interestingly these viruses were similar to 4d viruses found in Paris in 2001 to 2003, suggesting ongoing sexual transmission in the area.

New York…

Sexually transmitted HCV among HIV-positive gay men in America has lagged a few years behind the outbreaks in Europe, but has now established itself in New York. Two studies by the same team from Mount Sinai Hospital looked at aspects of the New York outbreak.

This team, led by Daniel Fierer, has previously documented alarmingly rapid liver fibrosis (scarring) in HIV-positive men who become infected with HCV, and a further study has confirmed this. In a cohort of 45 HIV-positive gay men, of whom 24 agreed to a liver biopsy, one had stage 3 fibrosis (one step short of cirrhosis), 18 had stage 2 fibrosis, three had stage 1, and two had none.

The profile of the men was very similar to the French patients; they were 40 years old on average and their median CD4 count was 525. Three-quarters were on antiretrovirals of whom 94%, 64% of the total, had an undetectable viral load. The average time since HIV diagnosis was seven years.

Four patients (13%) spontaneously cleared infection. All the others were offered pegylated interferon and ribavirin treatment. Of these 41, half chose to delay or refused treatment. Of the other 21, six are still awaiting treatment; of the 15 treated, eight achieved a sustained viral response, equivalent to a cure. Two failed treatment. The others are still being treated or evaluated.

Twenty-one men were matched with similar HCV-negative men to look at risk factors. The only factors that reached significance were unprotected receptive anal sex, with or without ejaculation, unprotected oral sex with ejaculation, use of sex toys, and ‘sex while high’. Again, fisting was not a significant risk factor but there was an interesting difference between receptive fisting, which was not a risk factor at all, and insertive fisting (the ‘top’), which was of borderline significance (p=0.07).

… and the UK

The second study (Fishman) compared the New York and UK outbreaks and looked at differences in the risk behaviours between 21 HCV/HIV-positive gay men (not the same cases as in the first study) and 60 UK cases previously reported by the HIV and Acute HCV Group (Danta 2007). Soberingly, from a UK perspective, the frequency of previously reported risk factors was a great deal higher in UK patients than for their New York counterparts.

UK patients were somewhat younger (average 36 versus 40) and had had HIV for less time (3.7 versus eight years), though their CD4 counts were the same, and a higher proportion of UK patients had undetectable HIV viral loads (59% versus 48%).

New York patients were more likely to have ever injected drugs (24% versus 3%), and were more likely to have shared injecting equipment (15% versus 1.7%) or shared crack pipes.

Apart from those factors, the UK patients had the lion’s share of risky behaviours. Just to take a few: 73% of UK patients had been fisting ‘tops’ and 57% ‘bottoms’ compared with 33% and 24% of New York men; 67% of UK men had practised fisting in a group compared with 12% of the New Yorkers; and 94% had had unprotected receptive anal sex in a group situation compared with 77% of the New York men. They had also used far more non-injectable recreational drugs: 80% versus 24% had used ketamine, 77% versus 38% cocaine, and 80% versus 38% had used ecstasy. A third had used LSD compared with none of the Americans. The greater use of drugs in the UK was called a “notable finding” by the researchers although, perhaps surprisingly, they did not look at methamphetamine use.

The UK men also had higher rates of STIs, with 85% having had a lifetime history of STIs compared with 38% of the Americans. All these differences were highly statistically significant.

Lastly, another US study found that only a minority of HIV-positive gay men are being screened for viral hepatitis of any kind in US HIV clinics. The study of eight clinics by Karen Hoover found that only 43% of men were tested for hepatitis A, 33% for hepatitis B, and 48% for hepatitis C. Practice varied but was “suboptimal” at all clinics, the researchers comment.

References

Van den Berk G et al. Rapid rise of acute HCV cases among HIV-1-infected men who have sex with men, Amsterdam.16th Conference on Retroviruses and Opportunistic Infections, Montreal. Poster abstract 804, 2009.

Ghosn J et al. Evidence for ongoing sexual transmission of hepatitis C (2006 to 2007) among HIV-1-infected men who have sex with men: France. 16th Conference on Retroviruses and Opportunistic Infections, Montreal. Poster abstract 800, 2009.

Fierer D et al. Characterisation of an outbreak of acute HCV infection in HIV-infected men in New York City. 16th Conference on Retroviruses and Opportunistic Infections, Montreal. Poster abstract 802, 2009.

Fishman S et al. Age and risky behaviors of HIV-infected men who have sex with men with acute HCV infection in New York City are similar, but not identical, to those in a European outbreak. 16th Conference on Retroviruses and Opportunistic Infections, Montreal. Poster abstract 801, 2009.

Danta M et al. Recent epidemic of acute hepatitis C virus in HIV-positive men who have sex with men linked to high-risk sexual behaviours. AIDS 21:983–991, 2007.

Hoover K et al. Hepatitis screening of HIV-infected men who have sex with men: 8 US clinics. 16th Conference on Retroviruses and Opportunistic Infections, Montreal. Poster abstract 803. 2009.