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Sexually transmitted hepatitis C virus superinfection in HIV/hepatitis C virus co-infected men who have sex with men
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[Research Letters]
"These are the first reports of sexually transmitted HCV superinfection in HIV/HCV-co-infected patients engaging in high-risk sexual behaviour."
AIDS:Volume 22(5)12 March 2008p 658-661
Ghosn, Jadea,b; Thibault, Vincentc; Delaugerre, Constancea; Fontaine, Helened; Lortholary, Oliviere; Rouzioux, Christinea; Pol, Stanislasd; Chaix, Marie-Laurea
aAP-HP, EA MRT 3620, Universite Paris Descartes, Department of Virology, Necker Hospital, Paris, France
bAP-HP, Department of Infectious Diseases, Pitie-Salpetriere Hospital, Paris, France
cAP-HP, Department of Virology, Pitie-Salpetriere Hospital, Paris, France
dAP-HP, Department of Hepatology, Necker Hospital, Paris, France
eAP-HP, Department of Infectious Diseases, Necker Hospital and Necker-Pasteur Centre for Infections Diseases, Paris, France.
Abstract
We report two cases of sexually transmitted hepatitis C virus (HCV) superinfection in HIV/HCV-co-infected patients with high-risk sexual behaviour. The two patients had chronic HCV and a history of sexually transmitted infections. HCV superinfection was confirmed by phylogenetic analysis. No risk factors for HCV were found except unprotected anal sex with multiple casual male partners. HCV serology and serum HCV RNA should be examined periodically in HIV-infected men who have sex with men engaging in high-risk sexual behaviours.
Infection with a divergent strain of hepatitis C virus (HCV), both intra and inter-genotype, in already HCV-infected patients (i.e. superinfection [1]) has been described in individuals who receive blood-product transfusion or organ transplants [2,3], after an invasive medical procedures [3] and among intravenous drug users [4]. To the best of our knowledge, however, sexually transmitted HCV superinfection has not yet been described. Here we report two cases of sexually transmitted HCV superinfection in HIV/HCV-co-infected patients with high-risk sexual behaviour.
Case report 1
A 41-year-old man chronically infected with HIV-1 and hepatitis B virus (HBV) since 1988 was hospitalized for acute cytolytic hepatitis in March 2001. His CD4 cell count was 500 cell/ƒÊl, his HIV-RNA level was 290 copies/ml (HIV Cobas Amplicor v1.5; Roche Diagnostic Systems, Inc., Branchburg, New Jersey, USA) on antiretroviral therapy including stavudine, lamivudine and efavirenz. At the time of presentation, his alanine aminotransferase (ALT) level was 1450 IU/ml (normal level < 65 IU/ml) associated with fever, asthenia and maculopapular rash. HBV viraemia was under the threshold of 0.7 million Eq/ml (branched DNA Quantiplex HBV; Bayer Diagnostics, Tarrytown, New York, USA). HCV serology and polymerase chain reaction (PCR) were negative (Cobas Amplicor HCV test v2.0; Roche; lower limit of detection 50 IU/ml). He reported unprotected sexual intercourse with multiple casual male partners. First, clinical diagnosis of secondary syphilis was proposed and confirmed by a positive serology (Treponema pallidum haemagglutination antibody titre of 1/10 000 and Venereal Disease Research Laboratory at 128 units). Second, hepatitis D virus (HDV) infection was suggested and confirmed with a positive HDV PCR [5] concomitantly to positive HDV serology. One year later (March 2002), elevation of transaminases led to the diagnosis of acute HCV, with a negative HCV serology but positive HCV viraemia (6.3 log10 IU/ml, Quantiplex HCV RNA 3.0; Bayer; lower limit of detection of 615 IU/ml). The HCV genotype was determined using both InnoLIPA HCV II and sequencing and phylogenetic analysis of NS5b gene as previously described [6]. HCV was genotype 4d, and the sequence clustered with sexually transmitted epidemic HCV genotype 4d strains circulating in the Paris area at that time [7], confirming that this patient engaged in high-risk sexual behaviour. In May 2003, HCV viraemia was detectable (4.6 log10 IU/ml) concomitantly with the re-occurrence of secondary syphilis. In December 2003, the patient presented again with secondary syphilis, and HCV viraemia was stable (4.4 log10 IU/ml) but with an unexpected genotype 3 virus. This HCV superinfection with a new genotype was confirmed 3 months later (March 2004). Other aetiologies of HCV infection were investigated but not found. The only risk factor was unprotected anal sex with multiple casual male partners. Contact tracing could not be performed as the patient was not able to identify his anonymous casual partners.
Case report 2
A 30-year-old man with HIV infection presented in April 2004 with a genital chancre. Primary syphilis was attested by positive serological test for T. pallidum (T. pallidum haemagglutination antibody titre 1/1280 and Venereal Disease Research Laboratory at 32 units).
At the time of presentation, his ALT level was 518 IU/ml. HCV serology was positive and HCV viraemia was detected by PCR (HCV load 6.51 log10 IU/ml, genotype 1a by both InnoLIPA HCV II and sequencing of NS5b). In the 6 months before the current syphilis episode he reported unprotected oral sex and anal intercourse with multiple casual male partners. The detection of HCV antibodies applied on a stored blood plasma sample taken 3 months earlier was negative. The patient was willing to participate in a retrospective epidemiological investigation conducted by the French national sentinel surveillance system in Parisian hospital wards on sexually transmitted HCV [8]. He answered questions about history of blood exposure, intravenous drugs, sexually transmitted infections and sexual behaviour. No other risk factor for HCV infection was found except unprotected anal sex. In addition, genotype 1 was detected in 22% of cases in this retrospective study [8]. He was started on pegylated interferon alpha-2a plus ribavirin, and HCV RNA was negative as early as 12 weeks on specific treatment. HCV RNA remained negative throughout the anti-HCV treatment course (i.e. 48 weeks) and at month 3 after treatment discontinuation. At month 6 posttreatment, HCV RNA was positive (genotype 1a) with concomitant secondary syphilis. The patient reported unprotected anal intercourse with bleeding during sex with multiple anonymous male casual partners during the previous 12 weeks, without identification of source partners.
Phylogenetic analysis was performed with NS5b nucleotide sequences (pretreatment and posttreatment sequences) and reference sequences of HCV subtypes (Los Alamos database). After alignment with the CLUSTAL W program V1.7, phylogenetic reconstruction was performed using a Kimura two parameters model and the neighbour-joining method with 1000 bootstrapped data sets. Bootstrap numbers of 800 or over are generally taken as positive evidence for the accuracy of a cluster of sequences [9]. In both cases, phylogenetic analyses showed distinct HCV strains (Fig. 1), thus suggesting, in the absence of other risk factors for HCV, sexually transmitted HCV superinfection.
Sexually transmitted HIV superinfection has been well documented [10]. In contrast, sexual HCV superinfection has not yet been described. These are the first reports of sexually transmitted HCV superinfection in HIV/HCV-co-infected patients engaging in high-risk sexual behaviour. Sexual intercourse seems to be the only important risk factor as no parenteral risk, recent hospitalization, history of acupuncture, ear piercing, tattooing, or sharing used razors or toothbrushes, was identified. Phylogenetic analysis confirmed the superinfection in the two cases; with a genotype 3 virus for patient 1, and with a distinct strain of genotype 1a in patient 2. In patient 2, the two sequences clustered independently, the first strain isolated in 2004 clustered with seven other 1a HCV strains with a bootstrap value of 900 and the second strain isolated in 2006 clustered with five other HCV strains with a bootstrap value of 900. This phylogenetic analysis ruled out the hypothesis of relapse of the first genotype 1a virus.
HCV sexual transmission is enhanced by high-risk sexual behaviour such as multiple casual partners [11], anal intercourse [12], syphilis and gonorrhea, and HIV co-infection [13]. HCV has been found to be detectable in semen with higher levels of HCV RNA in semen of HIV/HCV-co-infected patients than in HCV-monoinfected patients [14]. The incidence of HCV infection is increasing in HIV-infected men who have sex with men (MSM) [15].
Partial protection against re-infection was reported among HCV-seropositive intravenous-drug users who had spontaneously cleared viraemia [16]. In contrast, in individuals with established chronic HCV infection, immunological cross-protection is limited [1]. Our two patients did not spontaneously clear HCV. In addition, HIV-related deregulation itself might also limit immunological cross-protection against HCV superinfection.
Although the importance of sexually transmitted HCV superinfection remains limited in the general population, HCV/HIV-co-infected MSM with high-risk mucosal traumatic sexual practices should be aware of sexually transmitted HCV superinfection and should also benefit from education-based public health interventions. In addition, HCV serology and serum HCV RNA should be examined periodically in HIV-infected MSM who continue to engage in high-risk sexual behaviours.
Conflicts of interest: None.
References
1. Blackard JT, Sherman KE. Hepatitis C virus coinfection and superinfection. J Infect Dis 2007; 195:519-524.
2. Radkowski M, Wang LF, Vargas H, Wilkinson J, Rakela J, Laskus T. Changes in hepatitis C virus population in serum and peripheral blood mononuclear cells in chronically infected patients receiving liver graft from infected donors. Transplantation 2001; 72:833-838.
3. Laskus T, Wang LF, Radkowski M, Vargas H, Nowicki M, Wilkinson J, Rakela J. Exposure of hepatitis C virus (HCV) RNA-positive recipients to HCV RNA-positive blood donors results in rapid predominance of a single donor strain and exclusion and/or suppression of the recipient strain. J Virol 2001; 75:2059-2066.
4. Herring BL, Page-Shafer K, Tobler LH, Delwart EL. Frequent hepatitis C virus superinfection in injection drug users. J Infect Dis 2004; 190:1396-1403.
5. Deny P, Fattovich G, Le Gal F, Giustina G, Lecot C, Morsica G, et al. Polymerase-chain-reaction-based semi-quantification of hepatitis D viraemia in patients treated with high doses of alpha 2b interferon. Res Virol 1994; 145:287-295.
6. Sandres-Saune K, Deny P, Pasquier C, Thibaut V, Duverlie G, Izopet J. Determining hepatitis C genotype by analyzing the sequence of the NS5b region. J Virol Methods 2003; 109:187-193.
7. Serpaggi J, Chaix ML, Batisse D, Dupont C, Vallet-Pichard A, Fontaine H, et al. Sexually transmitted acute infection with a clustered genotype 4 hepatitis C virus in HIV-1-infected men and inefficacy of early antiviral therapy. AIDS 2006; 20:233-240.
8. Gambotti L, Batisse D, Colin-de-Verdiere N, Delaroque-Astagneau E, Desenclos JC, Dominguez S, et al. Acute hepatitis C infection in HIV positive men who have sex with men in Paris, France, 2001-2004. Euro Surveill 2005; 10:115-117.
9. Van der Kuyl AC, Cornelissen M. Identifying HIV-1 dual infections. Retrovirology 2007; 4:67.
10. Smith DM, Richman DD, Little SJ. HIV superinfection. J Infect Dis 2005; 192:438-444.
11. Feldman JG, Minkoff H, Landesman S, Dehovitz J. Heterosexual transmission of hepatitis C, hepatitis B, and HIV-1 in a sample of inner city women. Sex Transm Dis 2000; 27:338-342.
12. Halfon P, Riflet H, Renou C, Quentin Y, Cacoub P. Molecular evidence of male-to-female sexual transmission of hepatitis C virus after vaginal and anal intercourse. J Clin Microbiol 2001; 39:1204-1206.
13. Filippini P, Coppola N, Scolastico C, Rossi G, Onofrio M, Sagnelli E, Piccinino F. Does HIV infection favor the sexual transmission of hepatitis C? Sex Transm Dis 2001; 28:725-729.
14. Briat A, Dulioust E, Galimand J, Fontaine H, Chaix ML, Letur-Konirsch H, et al. Hepatitis C virus in the semen of men coinfected with HIV-1: prevalence and origin. Aids 2005; 19:1827-1835.
15. Ghosn J, Deveau C, Goujard C, Garrigue I, Saichi N, Galimand J, et al. Increase in hepatitis C virus incidence in HIV-1-infected patients followed up since primary infection. Sex Transm Infect 2006; 82:458-460.
16. Mehta SH, Cox A, Hoover DR, Wang XH, Mao Q, Ray S, et al. Protection against persistence of hepatitis C. Lancet 2002; 359:1478-1483.
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