Acute hepatitis C in HIV-infected men who have sex with men: an emerging sexually transmitted infection.

Since 2000 outbreaks of acute hepatitis C virus (HCV) among HIV-positive men who have sex with men (MSM) who denied injecting drug use have been reported from Europe, the United States, Canada and Australia. Given the burden of liver disease, in particular HCV, on the morbidity and mortality in HIV patients in the era of combination antiretroviral therapy, the rapid and significant rise in the incidence of HCV in the HIV-infected MSM population in high-income countries is alarming. This relates to a significant change in the epidemiology of HCV that has occurred, with HCV emerging as a sexually transmitted infection within this population. Work to date suggests that this permucosal HCV transmission results from high-risk sexual and noninjecting drug use behaviours, reopening the discussion on the importance of sexual transmission. Given this occurs almost exclusively in HIV-infected MSM, HIV probably has a critical role mediated either through behavioural and/or biological factors. Finally, the management of acute HCV in HIV infection is complicated by concomitant HIV infection and combination antiretroviral therapy. This review will synthesize the most recent epidemiological, immunological and management issues that have emerged as a result of the epidemic of acute HCV among HIV-infected MSM.

[1]  A. Charlett,et al.  Increase in diagnosed newly acquired hepatitis C in HIV-positive men who have sex with men across London and Brighton, 2002–2006: is this an outbreak? , 2007, Sexually Transmitted Infections.

[2]  C. Rouzioux,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 , 2006, AIDS.

[3]  C. Katlama,et al.  Liver fibrosis progression in human immunodeficiency virus and hepatitis C virus coinfected patients , 1999, Hepatology.

[4]  N. Terrault,et al.  Sexual activity as a risk factor for hepatitis C , 2002, Hepatology.

[5]  J. Kaldor,et al.  Prevalence, incidence and risk factors for hepatitis C in homosexual men: data from two cohorts of HIV-negative and HIV-positive men in Sydney, Australia , 2009, Sexually Transmitted Infections.

[6]  D. Vlahov,et al.  Protection against persistence of hepatitis C , 2002, The Lancet.

[7]  G. Caldito,et al.  Comparison of Hepatitis C Viral Loads in Patients with or without Human Immunodeficiency Virus , 2001, Clinical Diagnostic Laboratory Immunology.

[8]  F. D. De Rosa,et al.  A short course of pegylated interferon-alpha in acute HCV hepatitis. , 2007, Journal of viral hepatitis.

[9]  Michael J. Rausch,et al.  Effect of the interleukin‐6 C174G gene polymorphism on treatment of acute and chronic hepatitis C in human immunodeficiency virus coinfected patients , 2007, Hepatology.

[10]  T. Santantonio,et al.  Efficacy of a 24-week course of PEG-interferon alpha-2b monotherapy in patients with acute hepatitis C after failure of spontaneous clearance. , 2005, Journal of hepatology.

[11]  Chien-Jen Chen,et al.  Transmission of hepatitis C virus in Taiwan: Prevalence and risk factors based on a nationwide survey , 1999, Journal of medical virology.

[12]  Jacques Fellay,et al.  Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance , 2009, Nature.

[13]  Mila Lebedeva,et al.  Induction of a Striking Systemic Cytokine Cascade prior to Peak Viremia in Acute Human Immunodeficiency Virus Type 1 Infection, in Contrast to More Modest and Delayed Responses in Acute Hepatitis B and C Virus Infections , 2009, Journal of Virology.

[14]  M. Houghton,et al.  Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. , 1989, Science.

[15]  S. Vowler,et al.  Regulatory T Cells Suppress In Vitro Proliferation of Virus-Specific CD8+ T Cells during Persistent Hepatitis C Virus Infection , 2005, Journal of Virology.

[16]  J. V. D. van der Meer,et al.  Increase in HCV incidence among men who have sex with men in Amsterdam most likely caused by sexual transmission. , 2007, The Journal of infectious diseases.

[17]  Y. Hwang,et al.  Transmission of hepatitis C virus between spouses: the important role of exposure duration. , 1996, The American journal of gastroenterology.

[18]  R. Chung,et al.  Coinfection with HIV-1 and HCV--a one-two punch. , 2009, Gastroenterology.

[19]  I. Stolte,et al.  Hepatitis C virus infections among HIV-infected men who have sex with men: an expanding epidemic , 2009, AIDS.

[20]  J. Weber,et al.  Increasing incidence of acute hepatitis C in individuals diagnosed with primary HIV in the United Kingdom. , 2008, AIDS.

[21]  R. Geskus,et al.  Homosexual men change to risky sex when perceiving less threat of HIV/AIDS since availability of highly active antiretroviral therapy: a longitudinal study , 2004, AIDS.

[22]  E. Drucker,et al.  Epidemiology of chronic hepatitis C virus infection in sub-Saharan Africa. , 2002, The Lancet. Infectious diseases.

[23]  E. Suárez-Pérez,et al.  Sexual activity as a risk factor for hepatitis C in Puerto Rico. , 2004, Boletin de la Asociacion Medica de Puerto Rico.

[24]  C. Sabin,et al.  Non-AIDS-defining deaths and immunodeficiency in the era of combination antiretroviral therapy , 2009, AIDS.

[25]  Dieter Häussinger,et al.  Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. , 2002, The New England journal of medicine.

[26]  Charles M. Rice,et al.  HCV Persistence and Immune Evasion in the Absence of Memory T Cell Help , 2003, Science.

[27]  F. Chisari,et al.  Determinants of Viral Clearance and Persistence during Acute Hepatitis C Virus Infection , 2001, The Journal of experimental medicine.

[28]  B. Clotet,et al.  Sexual transmission of hepatitis C virus and its relation with hepatitis B virus and HIV. , 1990, BMJ.

[29]  B. Walker,et al.  Analysis of Successful Immune Responses in Persons Infected with Hepatitis C Virus , 2000, The Journal of experimental medicine.

[30]  S. Leiner Viral hepatitis in HIV infection. , 2007, The New England journal of medicine.

[31]  F. D. De Rosa,et al.  A short course of pegylated interferon‐α in acute HCV hepatitis , 2007 .

[32]  N. Afdhal,et al.  Duration of peginterferon therapy in acute hepatitis C: A randomized trial , 2006, Hepatology.

[33]  K. Demır,et al.  Sexual Transmission of HCV between Spouses , 2003, The American Journal of Gastroenterology.

[34]  C. Rouzioux,et al.  Hepatitis C virus in the semen of men coinfected with HIV-1: prevalence and origin , 2005, AIDS.

[35]  V. Schuermans,et al.  IMPAIRED NEUTROPHIL PHAGOCYTOSIS , 1974 .

[36]  Qilong Yi,et al.  Natural history of hepatitis C virus infection in HIV-infected individuals and the impact of HIV in the era of highly active antiretroviral therapy: a meta-analysis , 2008, AIDS.

[37]  M. Alary,et al.  Lack of evidence of sexual transmission of hepatitis C virus in a prospective cohort study of men who have sex with men. , 2005, American journal of public health.

[38]  C. B. Hare,et al.  Clinical presentation and course of acute hepatitis C infection in HIV-infected patients. , 2006, Journal of acquired immune deficiency syndromes.

[39]  J. Elford,et al.  High-risk sexual behaviour increases among London gay men between 1998 and 2001: what is the role of HIV optimism? , 2002, AIDS.

[40]  S. Bruisten,et al.  Reply to Richardson et al , 2008 .

[41]  C. Katlama,et al.  Treatment of Acute HCV Infection in HIV-Positive Patients: Experience from a Multicentre European Cohort , 2010, Antiviral therapy.

[42]  O. Pybus,et al.  Re-emergent hepatitis C viremia after apparent clearance in HIV-positive men who have sex with men: reinfection or late recurrence? , 2010, Journal of acquired immune deficiency syndromes.

[43]  M. Alter,et al.  Prevention of spread of hepatitis C , 2002, Hepatology.

[44]  N. Afdhal,et al.  Peginterferon alfa-2b therapy in acute hepatitis C: impact of onset of therapy on sustained virologic response. , 2006, Gastroenterology.

[45]  T. Santantonio,et al.  Recurrence of hepatitis C virus after loss of virus-specific CD4(+) T-cell response in acute hepatitis C. , 1999, Gastroenterology.

[46]  P. Klenerman,et al.  HCV–HIV Coinfection: Simple Messages from a Complex Disease , 2007, PLoS medicine.

[47]  T. Heeren,et al.  Influence of human immunodeficiency virus infection on the course of hepatitis C virus infection: a meta-analysis. , 2001, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[48]  J. Benito,et al.  Influence of HCV genotype and co‐infection with human immunodeficiency virus on CD4+ and CD8+ T‐cell responses to hepatitis C virus , 2007, Journal of medical virology.

[49]  F. Chiodo,et al.  Anti-hepatitis C virus antibodies amongst Italian homo-bisexual males , 1992, European Journal of Epidemiology.

[50]  A. Burchell,et al.  The prevalence and correlates of hepatitis C virus (HCV) infection and HCV-HIV co-infection in a community sample of gay and bisexual men. , 2009, International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases.

[51]  G. Ahlenstiel,et al.  The transforming growth factor-β high-producer genotype is associated with response to hepatitis C virus-specific therapy in HIV-positive patients with acute hepatitis C , 2008, AIDS.

[52]  H. Thio,et al.  A cluster of acute hepatitis C virus infection among men who have sex with men – results from contact tracing and public health implications , 2005, AIDS.

[53]  Hua-Lin Wu,et al.  Intrafamilial transmission of hepatitis C virus: The important role of inapparent transmission , 1994, Journal of medical virology.

[54]  J. Sidney,et al.  Cellular immune selection with hepatitis C virus persistence in humans , 2005, The Journal of experimental medicine.

[55]  N. Caporaso,et al.  Prevalence of anti-HCV among spouses and offspring of anti-HCV positive subjects: an Italian multicentre study. , 1995, The Italian journal of gastroenterology.

[56]  L. Kingsley,et al.  Hepatitis C virus infection in a male homosexual cohort: risk factor analysis. , 1996, Genitourinary medicine.

[57]  Michael J. Rausch,et al.  Pegylated interferon-alpha for the treatment of sexually transmitted acute hepatitis C in HIV-infected individuals. , 2006, Antiviral therapy.

[58]  T. Santantonio,et al.  Possible mechanism involving T-lymphocyte response to non-structural protein 3 in viral clearance in acute hepatitis C virus infection , 1995, The Lancet.

[59]  J. Kaldor,et al.  Characteristics and treatment outcomes among HIV-infected individuals in the Australian Trial in Acute Hepatitis C. , 2009, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[60]  H. Jessen,et al.  Treatment of acute hepatitis C infection in HIV‐infected patients: a retrospective analysis of eleven cases , 2005, Journal of viral hepatitis.

[61]  J. Elford Changing patterns of sexual behaviour in the era of highly active antiretroviral therapy , 2006, Current opinion in infectious diseases.

[62]  C. Graham,et al.  Pegylated interferon α therapy in acute hepatitis C: Relation to hepatitis C virus–specific T cell response kinetics , 2004, Hepatology.

[63]  D. Vlahov,et al.  Antibody to hepatitis C virus among cardiac surgery patients, homosexual men, and intravenous drug users in Baltimore, Maryland. , 1991, American journal of epidemiology.

[64]  J. Ghrayeb,et al.  Memory CD8+ T Cells Are Required for Protection from Persistent Hepatitis C Virus Infection , 2003, The Journal of experimental medicine.

[65]  Mario Roederer,et al.  Massive infection and loss of memory CD4+ T cells in multiple tissues during acute SIV infection , 2005, Nature.

[66]  R. Molenkamp,et al.  Frequent HCV reinfection and superinfection in a cohort of injecting drug users in Amsterdam. , 2009, Journal of hepatology.

[67]  Kenneth Koury,et al.  For Personal Use. Only Reproduce with Permission from the Lancet Publishing Group , 2022 .

[68]  M. Buti,et al.  HEPATITIS C VIRUS ANTIBODIES AMONG RISK GROUPS IN SPAIN , 1989, The Lancet.

[69]  A. Lackner,et al.  The gastrointestinal tract and AIDS pathogenesis. , 2009, Gastroenterology.

[70]  A. Samri,et al.  Acute hepatitis C in HIV-infected patients: rare spontaneous clearance correlates with weak memory CD4 T-cell responses to hepatitis C virus , 2009, AIDS.

[71]  A. Zanetti,et al.  Lack of Evidence of Sexual Transmission of Hepatitis C among Monogamous Couples: Results of a 10-Year Prospective Follow-Up Study , 2004, American Journal of Gastroenterology.

[72]  C. Walker,et al.  Adaptive immune responses in acute and chronic hepatitis C virus infection , 2005, Nature.

[73]  R. Biggar,et al.  Sexual transmission of hepatitis C virus: cohort study (1981-9) among European homosexual men. , 1990, BMJ.

[74]  Brad J. Wood,et al.  Rapid development of advanced liver fibrosis after acquisition of hepatitis C infection during primary HIV infection. , 2009, AIDS patient care and STDs.

[75]  J. Kaldor,et al.  Estimating progression to cirrhosis in chronic hepatitis C virus infection , 2001, Hepatology.

[76]  P. Marcellin,et al.  Hepatitis C virus infection in anti-HIV positive and negative French homosexual men with chronic hepatitis: comparison of second- and third-generation anti-HCV testing. , 2008, Liver.

[77]  Y. Gilleece,et al.  Increased numbers of acute hepatitis C infections in HIV positive homosexual men; is sexual transmission feeding the increase? , 2004, Sexually Transmitted Infections.

[78]  J. Kaldor,et al.  Spontaneous viral clearance following acute hepatitis C infection: a systematic review of longitudinal studies , 2006, Journal of viral hepatitis.

[79]  B. Gazzard,et al.  Transmission of Hepatitis C Virus Among HIV-Positive Homosexual Men and Response to a 24-Week Course of Pegylated Interferon and Ribavirin , 2005, Journal of acquired immune deficiency syndromes.

[80]  S. Riestra,et al.  Hepatitis C virus: evidence for sexual transmission. , 1991, BMJ.

[81]  M. Houghton,et al.  Recurrence of hepatitis C virus after loss of virus specific CD4+ T cell response in acute hepatitis C , 1998 .

[82]  Stuart C. Ray,et al.  Divergent and convergent evolution after a common-source outbreak of hepatitis C virus , 2005, The Journal of experimental medicine.

[83]  J. Kaldor,et al.  Effective treatment of injecting drug users with recently acquired hepatitis C virus infection. , 2010, Gastroenterology.

[84]  C. Bréchot,et al.  Epidemiological and virological analysis of couples infected with hepatitis C virus , 1999, Gut.

[85]  J. Desenclos,et al.  Acute hepatitis C infection in HIV positive men who have sex with men in Paris, France, 2001-2004. , 2005, Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin.

[86]  A. Mocroft,et al.  Influence of hepatitis C virus infection on HIV-1 disease progression and response to highly active antiretroviral therapy. , 2005, The Journal of infectious diseases.

[87]  C. Rouzioux,et al.  Increase in hepatitis C virus incidence in HIV-1-infected patients followed up since primary infection , 2006, Sexually Transmitted Infections.

[88]  R. Wolitski,et al.  Meta-analysis of cognitive-behavioral interventions on HIV-positive persons' mental health and immune functioning. , 2008, Health psychology : official journal of the Division of Health Psychology, American Psychological Association.

[89]  David B. Goldstein,et al.  Genetic variation in IL28B and spontaneous clearance of hepatitis C virus , 2009, Nature.

[90]  O. Pybus,et al.  Impact of HIV on host-virus interactions during early hepatitis C virus infection. , 2008, The Journal of infectious diseases.

[91]  B. Walker,et al.  The magnitude and breadth of hepatitis C virus-specific CD8+ T cells depend on absolute CD4+ T-cell count in individuals coinfected with HIV-1. , 2005, Blood.

[92]  Jennifer Y. Liu,et al.  Hepatitis C virus infection in sexually active homosexual men. , 1994, The Journal of infection.

[93]  S. Joekes,et al.  Hepatitis B and C Virus Sexual Transmission Among Homosexual Men , 1998, American Journal of Gastroenterology.

[94]  A. Theamboonlers,et al.  Interspousal transmission of hepatitis C in Thailand , 2003, Journal of Gastroenterology.

[95]  M. Sakamoto,et al.  Hepatitis C Virus Infection in Spouses of Patients with Type C Chronic Liver Disease , 1994, Annals of Internal Medicine.

[96]  R. Trivello,et al.  Hepatitis C virus infection in homosexual men: A seroepidemiological study in gay clubs in North-East Italy , 1991, European Journal of Epidemiology.

[97]  A. Branch,et al.  Liver fibrosis during an outbreak of acute hepatitis C virus infection in HIV-infected men: a prospective cohort study. , 2008, The Journal of infectious diseases.

[98]  C. Katlama,et al.  Efficacy of early treatment of acute hepatitis C infection with pegylated interferon and ribavirin in HIV-infected patients , 2006, AIDS.

[99]  F. Caprilli,et al.  Heterosexual and homosexual transmission of hepatitis C virus: relation with hepatitis B virus and human immunodeficiency virus type 1 , 1991, Epidemiology and Infection.

[100]  B. Berkhout,et al.  Risk of Hepatitis-Related Mortality Increased Among Hepatitis C Virus/HIV-Coinfected Drug Users Compared With Drug Users Infected Only With Hepatitis C Virus: A 20-Year Prospective Study , 2008, Journal of acquired immune deficiency syndromes.

[101]  Mardge H. Cohen,et al.  Factors associated with prevalent hepatitis C infection among HIV-infected women with no reported history of injection drug use: the Women's Interagency HIV Study (WIHS). , 2009, AIDS patient care and STDs.

[102]  S. Vermund,et al.  Risk Factors for Syphilis and Prevalence of HIV, Hepatitis B and C among Men Who Have Sex with Men in Beijing, China: Implications for HIV Prevention , 2009, AIDS and Behavior.

[103]  J. Kaldor,et al.  Hepatitis C virus infection in a large cohort of homosexually active men: independent associations with HIV-1 infection and injecting drug use but not sexual behaviour. , 1996, Genitourinary medicine.

[104]  M. Manns,et al.  Cellular immune responses persist and humoral responses decrease two decades after recovery from a single-source outbreak of hepatitis C , 2000, Nature Medicine.

[105]  C. Sabin,et al.  Sexual transmission of hepatitis C in MSM may not be confined to those with HIV infection. , 2008, The Journal of infectious diseases.

[106]  F. Caprilli,et al.  Incidence and Determinants of Hepatitis C Virus Infection Among Individuals at Risk of Sexually Transmitted Diseases Attending a Human Immunodeficiency Virus Type 1 Testing Program , 1997, Sexually transmitted diseases.

[107]  E. Thomson,et al.  Delayed anti-HCV antibody response in HIV-positive men acutely infected with HCV , 2009, AIDS.

[108]  K. Chayama,et al.  Molecular analysis of intraspousal transmission of hepatitis C virus. , 1995, Journal of hepatology.

[109]  Martin Fisher,et al.  Evidence of a large, international network of HCV transmission in HIV-positive men who have sex with men. , 2009, Gastroenterology.

[110]  M. Memon,et al.  Hepatitis C: an epidemiological review , 2002, Journal of viral hepatitis.

[111]  M. Stazi,et al.  Sexual transmission of the hepatitis C virus and efficacy of prophylaxis with intramuscular immune serum globulin. A randomized controlled trial. , 1997, Archives of internal medicine.

[112]  V. Soriano,et al.  Care of patients coinfected with HIV and hepatitis C virus: 2007 updated recommendations from the HCV-HIV International Panel. , 2007, AIDS.

[113]  Anne M Johnson,et al.  Recent epidemic of acute hepatitis C virus in HIV-positive men who have sex with men linked to high-risk sexual behaviours , 2007, AIDS.

[114]  J. Kaldor,et al.  Further evidence of HCV sexual transmission among HIV-positive men who have sex with men: response to Danta et al. , 2007, AIDS.

[115]  J. Altman,et al.  Viral Immune Evasion Due to Persistence of Activated T Cells Without Effector Function , 1998, The Journal of experimental medicine.

[116]  G. Everson,et al.  Telaprevir with peginterferon and ribavirin for chronic HCV genotype 1 infection. , 2009, The New England journal of medicine.

[117]  F. D. De Rosa,et al.  Twelve-week treatment of acute hepatitis C virus with pegylated interferon- alpha -2b in injection drug users. , 2007, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[118]  M. Manns,et al.  Early monotherapy with pegylated interferon alpha‐2b for acute hepatitis C infection: The HEP‐NET acute‐HCV‐II study , 2006, Hepatology.

[119]  O. Kirk,et al.  Liver-related deaths in persons infected with the human immunodeficiency virus: the D:A:D study. , 2006, Archives of internal medicine.

[120]  C. Trautwein,et al.  Treatment of acute hepatitis C with interferon alfa-2b. , 2001, The New England journal of medicine.

[121]  R. Weber,et al.  Unsafe sex and increased incidence of hepatitis C virus infection among HIV-infected men who have sex with men: the Swiss HIV Cohort Study. , 2005, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[122]  J. Stephenson,et al.  Behavioural predictors of subsequent hepatitis C diagnosis in a UK clinic sample of HIV positive men who have sex with men , 2006, Sexually Transmitted Infections.