Acute hepatitis C in HIV-infected men who have sex with men
Volume 5 Issue 4 Page 303 - July 2004
J Ghosn 1 , S Pierre-François 1 , V Thibault 2 , C Duvivier 1 , R Tubiana 1 , A Simon 3 , MA Valantin 1 , S Dominguez 1 , E Caumes 1 and C Katlama 1
1Département des Maladies Infectieuses et Tropicales, 2Laboratoire de Virologie, and 3Service de Médecine Interne, Centre Hospitalier Universitaire Pitié-Salpétrière, Paris, France
Hepatitis C virus (HCV) is usually transmitted via the parenteral route, but there are widely discrepant findings on its possible sexual transmission. Thus there are no recommendations concerning protected sex for couples in which only one partner is HCV-infected. Whether HIV or other sexually transmitted diseases could favour HCV transmission remains unclear, but recent data suggesting an increasing incidence of acute HCV in HIV-infected men underline the major public health implications of this issue.
Between June 2002 and July 2003, five HIV-infected homosexually active men presented with primary (n=4) and secondary (n=1) syphilis and concomitant abnormal liver function tests revealing acute asymptomatic HCV seroconversion. Other causes of acute viral hepatitis were inquired into and excluded. Highly at-risk sexual behaviour, including unprotected anal intercourse and unsafe oral sex, with concomitant syphilis, was found to be the only identifiable important risk factor for transmission of HCV.
Sexual transmission may be fuelling a significant increase in HCV seroconversions among HIV-infected men who have highly risky sexual behaviours. Given the recent data suggesting the spread of sexually transmitted infections among HIV-infected gay men, specific recommendations concerning safe sex are urgently needed.
The hepatitis C virus (HCV) is widespread, occurring in 1-2% of the population in developed countries, and more than 50% of infected subjects are chronically infected and may develop chronic hepatitis, cirrhosis and liver carcinoma . HCV is currently mostly transmitted by intravenous drug use or invasive medical procedures. Yet, among individuals infected by HCV, approximately 40% have no history of blood transfusion or intravenous drug use [2,3]. The role of sexual transmission in the spread of HCV infection has been a matter of debate for several years, with many studies suggesting its relevance [4-12], while other authors continue to discount it [13-15]. Co-infection with HCV is common in subjects infected with HIV . Whether HIV could increase the sexual transmission of HCV is unclear. Nevertheless, recent studies reported an increasing number of new HCV infections among HIV-infected men [16,17], as well as the return of syphilis and gonorrhoea . We report five cases of acute hepatitis C concomitant with primary or secondary syphilis in HIV-infected gay men attending our clinic.
A 32-year-old man with HIV infection since September 2000 presented in July 2003 with an anal chancre. He was treated for HIV with lamivudine, stavudine and ritonavir-boosted lopinavir and his last CD4 cell count was 408 cells/muL with plasma viral load <200 HIV-1 RNA copies/mL (Cobas Monitor 1.5; Roche, Meylan, France). The Treponema pallidum haemogglutination antibody (TPHA) titre was positive (1/320) with a Venereal Disease Research Laboratory (VDRL) at 16 units. Concomitantly, the alanine aminotransferase level was measured at 716 IU/mL (normal level between 16 and 35 IU/mL).
The serology of HCV was negative but a positive viraemia was detected by PCR (6.7 log10 IU/mL; Amplicor Roche Cobas V2.0, lower limit of detection 50 IU/mL). HCV serology was positive 2 weeks later (genotype 3). Other causes of acute viral hepatitis were excluded.
Over the 3 months before the current episode, he reported active physical relationships, including unsafe oral sex and anal intercourse with multiple male partners.
A 36-year-old man with HIV infection since 1993 presented in May 2003 with primary syphilis attested by Treponema pallidum-positive erosive lesions on his pharynx, concomitant with an acute hepatitis (alanine aminotransferase level 110 UI/mL). He was receiving HIV antiretroviral therapy with lamivudine, didanosine and ritonavir-boosted saquinavir, and his current CD4 cell count was 684 cells/muL with a plasma viral load <200 copies/mL. The serology of syphilis was positive with a TPHA titre of 1/10000 and VDRL 64 units. The HCV serology and HCV viraemia detected by PCR were positive (genotype 4, HCV load 6.07 log10 IU/mL). HCV serology was negative in December 2002. Other causes of acute viral hepatitis were excluded. Over the 6 months before his illness, he reported unprotected oral sex with multiple male partners.
A 30-year-old man with HIV infection presented in April 2003 with a genital chancre. Primary syphilis was attested by a positive serological test for T. pallidum (TPHA titre 1/1280 and VDRL 32 units).
He was treated for HIV with lamivudine, didanosine and ritonavir-boosted indinavir.
His last CD4 cell count was 414 cells/muL and his last viral load was <200 copies/mL. He had already had two previous episodes of syphilis (October 2001 and June 2002).
At the time of presentation, his alanine aminotransferase level was 518 IU/mL.
The serology of HCV was positive and HCV viraemia was detected by PCR (HCV load 6.51 log10 IU/mL, genotype 1a). In the 6 months prior to the current syphilis episode, he reported unprotected oral sex and anal intercourse with multiple casual male partners.
All the other aetiologies of HCV transmission were inquired into and not found. A test for HCV antibodies on a stored blood plasma sample taken 3 months before was negative.
A 41-year-old man regularly attending our clinic for his HIV infection presented in March 2003 with glossitis and two erosive lesions on his palate. He had been receiving antiretroviral therapy with didanosine, lamivudine and nevirapine since November 1999. His last CD4 cell count was 904 cells/muL and his last viral load was <200 copies/mL in January 2003.
Primary syphilis was attested by positive serology for syphilis (TPHA titre 1/20480 and VDRL 32 units). A lumbar puncture was performed, with a positive TPHA titre of 1/320 and a negative VDRL in the cerebrospinal fluid. Concomitantly, his alanine aminotransferase level was measured at 717 IU/mL. The serology of HCV was positive, and HCV replication was detected by PCR (HCV load 5.93 log10 IU/mL, genotype 4).
Over the 3 months before his illness, he self-reported highly at-risk oral sex and anal intercourse with multiple casual male partners. All the other aetiologies of HCV transmission were inquired into and not found. He was negative for HCV infection 3 months before as attested by the absence of anti-HCV antibodies in stored blood plasma samples.
A 45-year-old man living with HIV infection since December 1989 presented in June 2002 with a maculo-papular rash suggestive of secondary syphilis concomitant with an acute hepatitis. He was treated for HIV with lamivudine, zidovudine, and ritonavir-boosted-amprenavir, with a current CD4 cell count of 273 cells/muL and a plasma viral load <200 copies/mL.
The clinical diagnosis of secondary syphilis was confirmed by a positive serology (TPHA titre 1/20480 and VDRL 16 units), and alanine aminotransferase level was 626 IU/mL. The serology of HCV was positive and HCV replication was detected by PCR (HCV load 5 log10 IU/mL, genotype 3a). Other causes of acute viral hepatitis were excluded.
Over the 6 months before his illness, he had unprotected oral sex and anal intercourse with multiple partners. HCV serology was negative for the most recent stored blood plasma sample (2 months before).
There is now strong evidence confirming the role of sexual transmission in the spread of HCV. Indeed, HCV has been found to be detectable in semen [4,6]. Moreover, there is some molecular evidence of sexual transmission of HCV [5,10]. This sexual transmission seems to be enhanced by highly at-risk sexual behaviour such as multiple casual partners (>10 lifetime sexual partners) [11,19-22], age of first sexual intercourse <18 years , anal intercourse [5,19,23], history of or current syphilis and gonorrhoea [7,19], herpes simplex type 2 infection , and HIV co-infection [7,9,12,16,24]. A recent cohort study in France reported an increase in at-risk sexual behaviour among HIV-infected patients , while another study indicated the return of syphilis and gonorrhoea among the same population .
Our five HIV-infected patients were single, and reported unprotected anal intercourse and oral sex with multiple casual partners. They were all seronegative for HCV 3 to 5 months before the current diagnosis as attested by the absence of anti-HCV antibodies in stored blood plasma samples. The concomitant syphilis is consistent with their at-risk sexual behaviours and suggests that the presence of an anal or oral chancre may confer a risk for the sexual transmission of HCV. Moreover, sexual intercourse seems to be the only important risk factor as they all live alone and no parenteral or other risk factors for transmission of HCV, such as drug addiction, recent hospitalization, a history of acupuncture, ear piercing, tattooing, or sharing used razors and toothbrushes, were identified. For all five patients, acute HCV was not self-limiting 3 months after seroconversion, requiring a dual therapy with pegylated interferon alpha and ribavirine. It is interesting that, the five patients did not present with any symptom suggestive of hepatitis (e.g. jaundice or hepatalgia), and the diagnosis of acute hepatitis was made fortuitously. Hence, in HCV-seronegative HIV-infected gay men who have at-risk sexual behaviour, serological tests for HCV should be performed at least every year.
There is no evidence of a higher HCV viral load in the semen of HIV/HCV co-infected men than in the semen of HCV-infected patients [6,26]. However, HIV-infected men have significantly more seminal lymphocytes than HIV-seronegative men [27,28], which could yield a higher viral burden of HCV in the semen of HIV/HCV co-infected men in comparison to HCV-infected men, although not at the level of statistical significance. No association was found between HCV viral load in the semen of HIV/HCV co-infected individuals and antiretroviral treatment, decreased CD4 cell count, HIV viral load in semen or the blood viral loads of HIV and HCV . Nevertheless, HCV sexual transmission is significantly associated with HIV infection [12,16,19]. This strong association could be attributable to the specific sexual behaviour of HIV-infected gay men, with multiple casual partners and at-risk sexual behaviour. Moreover, the concomitant presence of another sexually transmitted infection such as syphilis, gonorrhoea or genital herpes could increase the risk of sexual transmission of HCV. Overall, HCV seroprevalence among HIV-infected patients ranges between 16% [29,30] and 30% [31,32], with a significant variability depending on risk factors. Indeed, HCV prevalence in HIV-infected intravenous drug users reaches 75%, while it is only 3% among HIV-infected gay men . Recent data suggesting the spread of sexually transmitted infections among HIV-infected gay men [18,34] underline the major public health implications of this issue.
It is interesting that, the widely discrepant findings on the sexual transmission of HCV may explain the lack of any recommendation concerning protected sex for couples in which only one partner is HCV-infected [35,36]. As regards sexual transmission of HCV, our five cases suggest the possibility of transmission of HCV during anal sexual intercourse or oral sex without safe-sex protections, in HIV-infected gay men engaging in highly risky sexual practices with multiple casual partners. Our findings suggest that people living with HIV should themselves be a target of prevention campaigns, with specific recommendations concerning protected sex. Further longitudinal studies are needed to monitor the role of sexual transmission in the possible spread of HCV in groups with specific features such as HIV-infected homosexually active men.
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