Double trouble – how hepatitis C is on the increase in HIV-positive gay men

Studies at CROI showed how hepatitis C is gaining ground, says Gus Cairns.

Last summer, an alarming study¹ presented at the International AIDS Conference in Mexico found that 20 out of a group of 157 HIV-positive gay men (18%) at a single clinic in Amsterdam had hepatitis C, a third of them with recent infection, and that hepatitis C prevalence was growing rapidly. In contrast only two of 532 HIV-negative men (0.4%) had the virus – a similar proportion to heterosexual women.

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.

We still don’t fully understand why some HIV-positive men are so vulnerable to hepatitis C, but several posters at the 16th Conference on Retroviruses and Opportunistic Infections (CROI) in Montreal last month confirmed the existence of new epidemics of the virus among gay men with HIV. They found that it sometimes had potentially severe health consequences, although treatment, if taken, was more often than not successful if started early.

The UK may have a particular public health problem here. A study from New York compared behaviours in local and UK gay men who had been infected and found that on a whole range of indicators the UK men were taking more health risks.

Another study from Amsterdam² confirmed that hepatitis C infection among HIV-positive men is a recent and rapidly growing problem there. Although cases of recent infection were not as common as in the other Amsterdam patient group, they were increasing exponentially. There were two in 2003, one in 2004, nine in 2005, 12 in 2006, six in 2007 and 14 in the first eight months of 2008. That means that by the end of 2008 one in every 66 HIV-positive gay men at the clinic might have become infected that year; 59% per cent of patients, based on the timing of previous negative hepatitis C tests, had had it for less than a year. The doctors presume it must be being transmitted sexually because none of the patients had classic risk factors such as injecting drug use or medical exposure to infected blood.

One study³ compared hepatitis C outbreaks in the UK and New York and looked at differences in the risk behaviours between 21 co-infected gay men in New York and 60 in the UK. The New York patients answered the same transmission risk survey that the UK patients had answered for a study in 2007.⁴

Soberingly, from a UK perspective, the majority of risk factors were a great deal higher on the European side of the Atlantic.

The New York patients were more likely to have ever injected drugs (24% versus 3%), and were more likely to have shared injection equipment (15% versus 1.7%): both ‘classic’ non-sexual risk factors.

The UK patients were somewhat younger (average 36 versus 40) and had had HIV for less time (3.7 versus eight years).

They also had the lion’s share of risky behaviours. For instance, three-quarters of UK patients had been fisting ‘tops’ and over half of them ‘bottoms’ compared with a third and a quarter of New York men, respectively. Two-thirds of the UK men reported fisting in a group situation compared with one in eight New Yorkers, and the vast majority (94%) had had unprotected receptive anal sex in a group situation compared with three-quarters of New York men.

They were also much heavier users of non-injectable drugs. Eighty per cent of UK patients versus 24% of New Yorkers had used ketamine, 77% versus 38% had used cocaine, and 80% versus 38% had taken 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. Having said this, one possible bias in the study is that, based as it was on a British questionnaire, they did not ask about the use of methamphetamine (crystal meth), which is much more common in the USA.

The UK men also had higher rates of sexually transmitted infections (STIs) with 85% having had a lifetime history of STIs compared with 38% of the Americans.

Another study⁵ was led by Daniel Fierer, who has previously documented alarmingly rapid liver fibrosis (scarring) in HIV-positive men who become infected with hepatitis C.⁶ In a different group of 45 HIV-positive gay men with recent hepatitis C infection, 24 agreed to having a liver biopsy. One had stage 3 fibrosis; this is significant liver scarring and is one step short of cirrhosis. Most of the others had stage 2 fibrosis, indicating more-than-mild liver damage.

Four patients (13%) spontaneously cleared hepatitis C infection. The other 41 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, and of the 15 treated eight achieved a sustained viral response, equivalent to a cure, while only two actually failed treatment. So at the very least, more than half of the patients who have undergone a course of treatment have found it successful.

Fierer also looked at risk factors by matching 21 men were matched with similar hepatitis C-negative men. 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’. Fisting, often the biggest suspect when it comes to sexual hepatitis C transmission, was not a significant risk factor (as long as the men were telling the truth) but there was an interesting and unexpected difference between being a ‘bottom’, which was not a risk factor at all, and being a ‘top’, which was of borderline significance (one chance in 14 the association was not real). All we can say about this is that how hepatitis C is being transmitted remains unclear, and may differ between groups.

A French study⁷ illustrated some of these similarities and differences. On one hand, the demographic and medical profile of the 45 New York and the 94 French patients was very similar. In both cases the men had an average age of 40, and 63 to 64% had an undetectable HIV viral load. French patients had had HIV for seven years and New York patients for ten.

On the other hand while in the other outbreaks documented at CROI, most of the patients had the genotype 1 variety of hepatitis C, the most common, half of the Paris patients whose full hepatitis C gene sequence was tested had the comparatively rare genotype 4. Furthermore all of these 15 patients had almost identical viral strains, suggesting rapid transmission within a closely-connected sexual network of gay men. Interestingly these viruses were closely similar to genotype 4 viruses found in Paris in 2001-03, suggesting ongoing sexual transmission in the area.

The study also highlighted the suspected link between being infected with another sexually transmitted infection and acquiring hepatitis C. Twenty out of the 32 patients with full lab data had an STI diagnosed at the same time as HCV, of which 14 had syphilis. Only five patients cited fisting as a behaviour.

Next month, HIV Treatment Update will look at reasons for the spread of hepatitis C among HIV-positive gay men and will also look at treatment prospects.

References

1. Urbanus A HCV is emerging as an STI among HIV-infected MSM: a threat to the MSM community? XVII International AIDS Conference, Mexico City, abstract THPDC203, August 7 2008.

2. 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.

3. 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.

4. 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.

5. 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.

6. Fierer D S et al. Liver fibrosis during an outbreak of acute hepatitis C virus infection in HIV-infected men: a prospective cohort study. J Infect Dis 198: 683 – 686, 2008.

7. 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.