CROI: More on sexual transmission of HCV in HIV+ gay men and heterosexual women

London and Brighton

To date, more than 200 HIV-positive gay men in London and around 25 HIV-positive gay men in Brighton have been diagnosed with sexually-transmitted HCV. Mark Danta from London's Royal Free Hospital provided an update on risk factors associated with sexual transmission of HCV in 111 HIV-positive gay men diagnosed in London and Brighton between October 2002 and August 2005.

Dr Danta previously reported in detail about this cohort last November at the American Association for the Study of Liver Diseases meeting in San Francisco.

The HIV-positive gay men with HCV coinfection had three times as many sexual partners in the previous twelve months compared with HIV-positive gay men without HCV coinfection (30 vs. 10, p <0.001).

Highly statistically significant (all p <0.001) risk factors seen more frequently in the HCV coinfected men compared with men without HCV coinfection included:

• unprotected receptive and insertive anal intercourse
• mucosally traumatic practices, including receptive and insertive fisting, and use of sex toys.
• group sex
• and sexual activity under the influence of 'club' drugs (including 'crystal meth', ketamine, GHB, poppers, LSD, and ecstasy).

Insertive or receptive anal intercourse without condoms and/or insertive or receptive fisting without gloves were all found to increase the risk of acquiring HCV sexually, with group sex situations greatly increasing the risk. Dr Danta said that the risk was increased ninefold if two of the above four sexual practices took place during group sex. But if three or all four of these sexual practices took place during group sex the risk increased more than 23-fold.

More data on the sexual transmission of hepatitis C virus (HCV) from London, Brighton and Amsterdam were presented earlier this month at the Thirteenth Conference on Retroviruses and Opportunistic Infections (CROI) in Denver suggesting that it occurs primarily amongst HIV-positive gay men who practice unprotected anal sex and/or 'fisting' with many sexual partners. However, sexually transmitted HCV does also occur heterosexually: a French study reports that two HIV-positive women in a cohort of 402 recently-infected HIV-positive men and women probably acquired HCV through vaginal sex.

Since 2002, when AIDS Treatment Update reported on a previously unrecognised oubreak of acute HCV infection amongst gay HIV-posititive men in London, evidence continues to mount that although injection drug use (IDU) is the most frequent mode of HCV transmission worldwide, hepatitis C is also being sexually transmitted.

Three presentations at CROI focused on this area, providing further insight into specific risk factors and which populations might be particularly at risk.

Amsterdam

Sexually transmitted HCV is also occuring in Amsterdam, according to Professor Roel Coutinho of Amsterdam's Municipal Health Service. By retrospectively testing 1836 gay men participating in the Amsterdam Cohort Study between 1984 and 2003 for HCV antibodies they found that HCV incidence in HIV-infected gay men increased tenfold after the year 2000 compared with the 15 years before (0.08/100 person-years vs. 0.87/100 person-years, p = 0.001).

The investigators also obtained serum samples of gay men who had been diagnosed with an acute HCV infection from all Amsterdam hospitals between 2003 and 2005. A combined 26 cases of acute HCV coinfection were seen, 25 (96%) of which were in HIV-positive men.

Twenty of the 25 men were interviewed to assess sexual risk factors. Ten (50%) reported fisting and thirteen (65%) were also diagnosed with mucosa-damaging sexually transmitted infectious, including lymphogranuloma venereum (LGV), syphilis, or HSV-2 along with their HCV infection.

Phylogenetic analysis of HCV genotypes in 24 of the men found two large clusters: one of genotype 4 (45%) and one of genotype 1 (38%). Two smallers clusters of genotype 3 and genotype 1 were also seen. Since the genetic make-up of these HCV genotypes did not match HCV isolated from other Dutch risk groups, their data provide strong evidence supporting the introduction and sexual transmission of different co-circulating HCV genotypes.

During the question and answer session, Professor Coutinho commented that the HCV infections seen so far are probably "the tip of the iceberg", since "we only found these cases through the clear attention of the doctor."

Attempting to explain why an increased risk of HCV sexual transmission has only been seen in recent years when unprotected sex occurred in the 1970s and 1980s, before safer sex education, a representative from New York's Department of Health suggested that serosorting may partially explain the phenomenon.

Since 2000, many more men chronically infected with HIV have been able to meet via the internet for 'bareback' or 'poz' parties, and this may partially explain the epidemiology of sexual HCV transmission. In addition, fisting and more esoteric sexual practices that expose sexual partners to blood have become more commonplace during this period, compared with the 1970s/80s.

Comment

Is the heterosexual transmission of HCV amongst HIV-infected women a concern? Data are conflicting.

A large study from the United States published in 2003 examined stored blood samples taken between 1994 and 1999 from 2059 HIV-positive women and 569 HIV-negative women who were enrolled in the Women’s Interagency HIV Study (WIHS). They found no evidence of the sexual transmission of HCV in any of the women enrolled in their study.

However, another study published in the same year, examining the prevalence of seven chronic viral infections in 871 HIV-positive women and 439 HIV-negative women enrolled in the US HIV Epidemiology Research Study (HERS) between 1993 and 1999, found possible evidence for the sexual transmission of HCV. Here, 10.5% of the women coinfected with HCV had sex alone as a risk factor for the infection. The investigators wrote that their increased risk “might be explained by the higher number of sex partners” women in this study had, as well as “a higher prevalence of HCV infection in sex partners”.

Interestingly, many of the coinfected women in the HERS study also had genital herpes (HSV-2) infection, and an Indian study from 2003 also found that genital ulcers, including those caused by HSV-2, increased the risk of HCV coinfection four-fold.

Since the number of reported lifetime sexual partners was low in the Indian study (between one and six, although 95% of sex was unprotected) that study suggests that factors which increase the risk of an HIV-positive woman's risk becoming infected with HCV depends on the prevalence of HCV in the population, as well as infections that cause genital ulcer disease.

This would suggest that female HIV-positive sexual partners of current or former IDUs are more likely to be at risk of acquiring HCV sexually, since HCV is highly prevalent amongst IDUs.

France

A poster presentation from France suggests that HIV-positive women are also being infected heterosexually with HCV.

The French PRIMO Cohort includes patients who were diagnosed with primary HIV infection, and this study included the 402 of the 605 cohort members with at least 18 month's follow-up (median 4 years) providing a follow-up period of 1404 person-years.

HCV seroconversion was observed in three men and two women, with four of the five acquiring HCV after January 2002. The corresponding incidence rate for men was 2.61 per 1000 person-years and 7.81 per 1000 person-years for women.

The investigators found that the only identified risk factor for HCV acquisition in all five individuals was "unsafe sex", although they do not define the term. They also only report "inconstant condom use" in one of the women.

Although the heterosexual tranmission of HCV is not a new finding, and the investigators only identify two women, their study does suggest that sexually-acquired HCV may be occuring more frequently than previously thought – albeit at a low rate – amongst HIV-positive women during the past few years.