Sexually transmitted HCV in HIV positive and negative gay men

Simon Collins, HIV i-Base

Several studies at BHIVA 2014 focused at HCV sexual transmission, together with the social complications this brings.

Of note, two studies reported sexual transmission of HCV to HIV negative gay men.

Sexual HCV transmission to HIV negative gay men

In an oral presentation, Dr Juan Tiraboschi, Guy’s & St Thomas’, reported on acute HCV infections that were detected during the PROUD study. [1]

This is an ongoing PrEP study that will randomise approximately 500 HIV negative gay men at risk of HIV to either immediate or deferred use of daily oral tenofovir/FTC. HCV testing was not routinely incorporated into the study design because the risk of sexual HCV testing has generally only been reported in HIV positive gay men. Neither positive HCV antibody status nor raised LFT levels were exclusion criteria for entering PROUD.

However, 160/393 (41%) patients enrolled in PROUD by December 2013, had been tested for HCV at least once during follow-up and 5/160 were found to have recent HCV infection. All men had a negative HCV test three months earlier. This correlates to an incidence of 3.1% of the tested cohort or 1.3% of the cohort as a whole.

The five cases (3 in the immediate PrEP arm and 2 in the deferred arm) ranged in age from 24 to 64 years old. HCV was diagnosed during the screening period in one person and from 7 to 64 days since enrollment for the others. Mean HCV RNA was 6.2 log copies/mL (range 9000 to 25,000,000). Only one patient was symptomatic (jaundice) with HCV testing prompted by recent risk behaviour including having an HCV positive partner for the others. All men reported anal sex (without condoms). One man was diagnosed with rectal chlamydia and gonorrhea and another man reported injecting drug use.

The high and unexpected rates of HCV in high risk gay men, lead the researchers to conclude that HCV testing should be considered in PrEP studies.

A separate presentation from PROUD reported a history at baseline of high rates of other STIs showing that the study has recruited an appropriately high risk population. [2]

Self-reported STIs history for the previous 12 months included 25% (of the first 310 participants) each reported having had rectal, oral or urethral gonorrhoea (some people had more than one), 15% reported urethral and/or oral chlamydia, 10% reported syphilis, 9% genital warts and 2% LGV.

The second HCV study was a retrospective review of acute HCV in HIV negative men diagnosed over four years at the sexual health clinic of the Chelsea and Westminster Hospital from January 2010 and December 2013. Of 36 acute HCV diagnosed by positive HCV antibody, ten were RNA negative at baseline and categorised as spontaneously cleared. Acute HCV was diagnosed by previous recent negative antibody status for 9 people, by positive HCV RNA in 4 people and by risk history in another 13. [3]

Risk factors included having an HCV positive partner (27%), multiple sexual partners in the previous three months (median 2, range 1- 60), group sex (35%), fisting (35%), recreational drug use (58% including cocaine, GHB, mephedrone, crystal methamphetamine and ketamine), intravenous use (27%). Most people reported having anal sex without condoms (85%) and 30% had an additional STI.

Genotype was only documented in 13 individuals (12 genotype 1 and 1 genotype 4). Three men (11%) with positive RNA at baseline spontaneously cleared HCV. Nine men were treated with pegylated interferon +/- ribavirin, of whom, seven achieved SVR clearance. Of the remaining 14 men, 6 had persistent infection, and 8 were lost to follow up.

Implications of detectable HCV RNA in semen

Although blood-to-blood transmission of HCV appears more plausible as the route for sexual HCV transmission, an oral presentation looked at HCV levels in semen, looking for differences by HIV status and in acute compared to chronic HCV infection. [4]

Of 66 HCV positive men, 40/66 were HIV positive, Of the HIV positive men, 18 with acute HCV (median duration 3.5 months (IQR 2.0, 6.3) and 22 had chronic HCV. Of these, 35/40 were on ART with undetectable HIV viral load. All 26 HIV negative men had chronic HCV infection.

At baseline, HCV RNA was detected in semen sample from 29 (43.9%) at median 2.1 log IU/mL (IQR 1.8-2.6) with no relationship reported for either HIV status or acute compared to chronic HCV. This was approximately 4 logs lower than median plasma HCV RNA (5.5 logs IU/mL; IQR 5.5, 6,5) again without differences between groups. For people in acute HCV infection, plasma RNA levels were higher (approximately 6.1 vs 4.2 log IU/mL) in those with detectable levels in semen, though this was not observed for with groups with chronic HCV.

HCV shedding in semen was intermittent in 40% of men. Of 35 men with a follow-up sample (at median 4.5, IQR 3.8-6.5 months), HCV was detected in semen in at least one sample for 26/35 men (74%), and in both samples in 12 men (34%).

Social complications of coinfection

Two posters looked at the social issues associated with a new HCV diagnosis.

Saxon and colleagues reported on the difficulty of disclosure of HCV status to new sexual partners experienced by HIV positive gay men in Manchester. [5]

Only 16/52 men with coinfection agreed to participate in a semi-structured, face-to-fact interview, about HCV disclosure to sexual partners. At the time of the interview, most (12/16) were no longer HCV positive. Four men reported abstinence while HCV positive, highlighting the impact of HCV in this group. HCV disclosure was reported always, mostly, sometimes and never, by 3, 2, 4 and 3 men respectively.

Perceived stigma of HCV and fear of rejection or reaction to disclosure, but also safer sex and behaviour and lack of HCV awareness were associated with non-disclosure. Themes for disclosure included increasing HCV awareness, fear of legal prosecution, responsibility, trust and feelings for partner.

These results suggest that a larger study may be worthwhile, perhaps using an anonymised survey, especially given the low numbers of men agreeing to participate.

Also concerned with anecdotal reports of stigma associated with hepatitis C, Archibold and colleagues at the Bloomsbury Clinic in London ran two peer-led workshops for HIV positive people who were newly diagnosed with HCV. [6]

Evaluations completed by 16 people generally reported generally high satisfaction scores associated with acceptance of their HCV diagnosis and a better understanding of treatment. Greater confidence about disclosure scored 3.13 (out of a maximum 4.00)

The workshop reported that isolation felt by HIV positive men with coinfection led to wider psychological issues causing lack of confidence and depression, and that this was helped by this format for support.

Comment

Studies on the incidence of HCV sexual transmission in HIV negative men have not reported a consistent pattern. In Brighton, 9 cases of acute HCV were in HIV negative men and 5 in men who HIV status was unknown (though some of these men were likely to have become HIV positive at the same time, [5] whereas other surveillance data have not reported this.

These studies add to the complexity of understanding HCV sexual transmission. As the biological route is not yet identified this limits the accuracy of advice for avoiding infection or transmission. Currently, the plausibility is higher for blood-blood exposure during sex explaining these cases than for a new concern about the infectiousness of semen and/or other sexual fluids.

References

Unless stated otherwise, references are to the 3rd Joint BHIVA/BASHH Conference, 3-6 April 2014, Liverpool. A PDF file of the abstract book is available at:
http://www.bhiva.org/documents/Conferences/2014Liverpool/AbstractBook2014.pdf (PDF)

Tiraboschi J et al. Acute Hepatitis C in the PROUD pilot study. 3rd Joint BHIVA/BASHH Conference, 3-6 April 2014, Liverpool. Oral abstract O45.
Dolling D et al. Who accesses PrEP? An analysis of baseline data in the PROUD pilot study. 3rd joint BHIVA/BASHH Conference, 3-6 April 2014, Liverpool. Oral abstract abstract 043.
McFaul K et al. Acute hepatitis C infection in HIV-negative men who have sex with men. 3rd Joint BHIVA/BASHH Conference, 3-6 April 2014, Liverpool. Poster abstract 384.
Bradshaw D et al. Seminal HCV RNA level may mirror dynamics of plasma HCV RNA in HIV-infected men with acute HCV. 3rd Joint BHIVA/BASHH Conference, 3-6 April 2014, Liverpool. Oral abstract O23.
Saxon C et al. Do HIV/hepatitis C co-infected men who have sex with men disclose their status to sexual partners? 3rd Joint BHIVA/BASHH Conference, 3-6 April 2014, Liverpool. Poster abstract 107.
Archbold J et al. Impact of peer-led support for HIV/hepatitis C coinfected MSM. 3rd Joint BHIVA/BASHH Conference, 3-6 April 2014, Liverpool. Poster abstract 389.
Richardson D et al. Sexual transmission of hepatitis C in MSM may not be confined to those with HIV infection. J Infect Dis 2008; 197:1213–1214.
http://jid.oxfordjournals.org/content/197/8/1213.full.pdf+html

Note: the STI data from PROUD and reference 2 was added subsequent to the initial publication of this report.