CROI: Recurrent hepatitis C in HIV-positive gay men: relapse or reinfection?

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Genetic analysis suggests that HIV-positive gay men in London are being re-infected with sexually transmitted hepatitis C virus rather than experiencing relapse after treatment, according to a presentation at the Fifteenth Conference on Retroviruses and Opportunistic Infections in Boston on Monday.

There have been several outbreaks of apparently sexually transmitted hepatitis C infection amongst mostly HIV-positive men who have sex with men reported since the early 2000s. The largest epidemic is centred in the south of England (London and Brighton), but smaller clusters have also been seen in other major northern European cities, including Amsterdam, Paris, and several cities in Germany, as well as in Australia.

It is thought that men who have already been diagnosed as HIV-positive and have frequent, unprotected or ‘hard’ sex with other HIV-positive men (often in groups, and often under the influence of recreational drugs such as ketamine or GHB) are most at risk of acquiring hepatitis C via sex.



In HIV, synonym for superinfection. In hepatitis C, used when someone who has been cured of the virus is infected with hepatitis C again.

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).


The return of signs and symptoms of a disease after a patient has been free of those signs and symptoms. 

lymphogranuloma venereum (LGV)

A sexually transmitted infection that can have serious consequences if left untreated. Symptoms include genital or rectal ulcers.


A sexually transmitted infection caused by the bacterium Treponema pallidum. Transmission can occur by direct contact with a syphilis sore during vaginal, anal, or oral sex. Sores may be found around the penis, vagina, or anus, or in the rectum, on the lips, or in the mouth, but syphilis is often asymptomatic. It can spread from an infected mother to her unborn baby.

However, data from Brighton presented at last year’s Retrovirus conference showed that a small number of HIV-negative gay men are being diagnosed with hepatitis C as well; this report suggested that most of these men also become HIV-positive within a short time. Further, at the 2006 conference, researchers reported a few cases of apparent sexual transmission of hepatitis C to HIV-positive heterosexual women.

In a Monday afternoon session on HIV and hepatitis C coinfection, Rachael Jones from London’s Chelsea and Westminster Hospital presented a late-breaker study that examined the incidence of subsequent acute hepatitis C infection amongst HIV-positive gay men who had previously been infected with hepatitis C and who had achieved sustained response following treatment of their first acute hepatitis C infection.

The study combined data from the two largest HIV treatment centres in London – Chelsea and Westminster Hospital and the Royal Free Hospital. Of 211 HIV/hepatitis C coinfected individuals, 16 were identified as having two or more episodes of hepatitis C infection. Unlike some diseases, hepatitis C infection does not produce a lasting immune response that can protect against subsequent reinfection.

All were HIV positive gay or bisexual men with no known history of injecting drug use. The men had been diagnosed with HIV for an average of four years (range 1 – 17 years). The average age at first H hepatitis C infection was 38 years (range 26 – 51 years) and the average CD4 cell count at that time was 476 cells/mm3, indicating well preserved immune function.

All the men had previously undergone hepatitis C treatment with pegylated interferon plus ribavirin during their first acute infection, and had achieved sustained virological response, defined as undetectable HCV viral load on at least two measurements. While sustained virological response—more typically defined as continued undetectable hepatitis C RNA six months after completion of treatment—does not indicate complete hepatitis C eradication, it is usually considered a “cure,” and relapse more than six months after finishing interferon-based therapy is uncommon.

Subsequent hepatitis C infection in these men was detected following an increase in liver enzymes (ALT) during regular HIV clinic follow-up. Eleven of the 16 men were on antiretroviral therapy for HIV therapy at the time, and the average CD4 count was 499 cells/mm3. The average duration of sustained response before subsequent detection of hepatitis C viraemia was 28 months (range 6 – 55 months).

The investigators were able to obtain amplifiable, paired hepatitis C samples (from the first and subsequent HCV episodes) from eight of the men (all hepatitis C genotype 1). They performed a phylogenetic analysis to determine the likelihood that the two samples were related and to provide information about clusters of infection.

In two of the eight men, the samples were very closely related, suggesting either late relapse or subsequent re-infection from a common source. The other six men were found to have divergent paired sequences, suggesting that they were re-infected with a second hepatitis C strain of the same genotype.

In addition, the analysis found a clustering of most of the analysed hepatitis C strains which, the researchers suggested, may mean that a small “closed population” of gay HIV-positive men are re-infecting each other after treatment.

Importantly, the investigators found that all but two of the men with suspected hepatitis C reinfection had a concurrent sexually transmitted infection—usually syphilis (ten episodes), but also gonorrhoea (six cases) and new or recurrent herpes (three cases). This finding adds weight to their assertion that the men were continuing to practice sex that put them at a high risk of acquiring HCV.

Last year, Dr Mark Nelson, of the Chelsea & Westminster told the August/September issue of AIDS Treatment Update that he had observed syphilis and lymphogranuloma venereum (LGV) in many of his patients who had acquired hepatitis C via sex, both of which, he said, “make HIV and hepatitis C transmission even more likely.”

He added that the continued sexual transmission of hepatitis C amongst HIV-positive men “underlines the importance of safer sex messages for HIV-positive men. Some men are having condomless sex because they perceive that they won’t pass on HIV to someone who already has HIV, or if they have an ‘undetectable’ viral load for HIV, they can’t pass on HIV to anyone. But it does seem they’re passing on—and getting—hepatitis C.”

Along these lines, Dr Jones suggested that healthcare providers are “failing our patients,” since they are becoming infected with hepatitis C not once, but multiple times.

Indeed, she added, after the current presentation had been prepared, the researchers learned that two of the men who had been treated for a second episode of acute hepatitis C had become reinfected (or relapsed) yet a third time.

“We need a much stronger public health information and screening program” for hepatitis C, she said.


Jones R et al. Hepatitis C viremia following sustained virological response to pegylated interferon and ribavarin in HIV+ men who have sex with men –re-infection or late relapse? Fifteenth Conference on Retroviruses and Opportunistic Infections, Boston. Abstract 61LB, 2008.