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Sexual Transmission of Hepatitis C for MSM & Heterosexual Women Facilitated by STDs, HIV, Unsafe Sex Practices
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Reported by Jules Levin
13th CROI
Denver, Feb 5-8, 2006
Women Are at Risk for Acquiring HCV by Sexual Transmission
"Increase in HCV Incidence in HIV-1-infected Women and Men Followed in the French PRIMO Cohort"
J Ghosn1, C Goujard2, C Deveau3, J Galimand1, I Garrigue4, N Saichi3, C Delaugerre1, L Meyer3, C Rouzioux1, Marie-Laure Chaix*1, and PRIMO Cohort Study Group (ANRS CO 06)
1Univ Hosp Necker, Paris, France; 2INSERM E109, Univ Hosp Bicetre, Le Kremlin-Bicetre, France; 3INSERM U569, Univ Hosp Bicetre, Le Kremlin-Bicetre, France; and 4CHU Pellegrin, Bordeaux, France
An increase in sexually transmitted infections, and in the incidence of sexually transmitted hepatitis C infections (HCV) in HIV-infected men who have sex with men have recently been reported. The study objective was to investigate HCV incidence among HIV-1-infected patients, identified at the time of primary HIV infection and enrolled in the French PRIMO Cohort between 1996 and 2005.
They included patients with a minimum follow-up of 18 months for this study. HCV antibody tests were done at inclusion and on the latest available sample.
Results
To date, 605 patients had been included in the French Primo Cohort, 27 of 605 (4.46%) had positive HCV antibodies at inclusion. Of 605 patients, 402 had at least an 18-month follow-up and were eligible for the present analysis. At inclusion, HCV antibodies were detected in 23 of the 402 patients (4 of 75 women [5.33%] and 19 of 327 men [5.80%]). For these 402 patients, median follow-up was 48 months (range 18 to 104), providing a follow-up period of 1404 person-years. HCV seroconversion was observed in 5 patients (3 men and 2 women) corresponding to an HCV incidence rate of 3.56 per 1000 person-years. Incidence rate for men and for women was 2.61 and 7.81 per 1000 person-years, repectively. The incidence rate before January 2002 was 1.81 per 1000 person-years (n = 1 of 5 patients) and 4.69 per 1000 person-years (n = 4 of 5 patients) after January 2002 (p = 0.24). In all 5 patients, classical risk factors for HCV infection (injection drug users, blood transfusion, recent invasive medical procedures surrounding seroconversion period) were inquired into and not found. The only identified risk factor for HCV acquisition was unsafe sex. One woman reported inconstant condom use, 2 men had concomitant syphilis at the time of acute HCV, and the remaining man reported at-risk sexual behaviour.
The authors concluded that the increase in the incidence of acute HCV infection in recently HIV-infected patients confirms the shift in sexual behavior in the recent years. We report a high HCV incidence among HIV-infected women, suggesting that women are also at-risk of acquiring HCV via the sexual route. Repeated testing for HCV antibodies should be done in HCV-negative HIV-infected patients and specific recommendations concerning protected sex clearly provided for men and women living with HIV.
What about the risk for sexual transmission among women in the USA? This has not been well studied. But here is what one published study said: authors suggest 10.5% sexual transmission among women in this study population in the USA.
"Prevalence of and Risk Factors for Viral Infections among Human Immunodeficiency Virus (HIV)-Infected and High-Risk HIV-Uninfected Women" JID May 1, 2003
Cynthia T. Stover, et al for the HIV Epidemiology Research Study Groupa. 1Emory University, 2National Center for HIV, STD and TB Prevention, Division of HIV/AIDS Prevention, and 3Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia.
ABSTRACT: Viruses that can persist in the host are of special concern in immunocompromised populations. Among 871 human immunodeficiency virus (HIV)-infected and 439 high-risk HIV-uninfected women, seroprevalences of cytomegalovirus, hepatitis B virus, hepatitis C virus, and herpes simplex virus types 1 and 2 and prevalence of human papillomavirus DNA in cervicovaginal lavage fluids were all >50% and were 2-30 times higher than prevalences in the general population. Prevalences were highest among HIV-infected women, of whom 44.2% had >5 other infections, and were relatively high even among the youngest women (age 1625 years). In multivariate analyses, viral infections were independently associated not only with behaviors such as injection drug use and commercial sex but also with low income, low levels of education, and black race. Disadvantaged women and women who engage in high-risk behaviors are more likely to be coinfected with HIV and other viruses and, thus, may be at high risk of serious disease sequelae.
HERS followed up a cohort of women over a period of 6 years (19931999) to examine the biological, psychological, and social effects of HIV infection on women's health. The study enrolled 871 HIV-infected and 439 demographically matched (i.e., by age, race/ethnicity, and study site) HIV-uninfected women aged 1655 years in 4 US cities. By design, approximately two-thirds (66.5%) of the women in the study were infected with HIV, and more than one-half (58.5%) reported having injected drugs. Black was the dominant racial group (58.2%), followed by white (24.2%) and other (17.6%). Almost one-half of the women (42.7%) had less than high school education, and approximately three-fourths (72.6%) had an annual income of <$12,000. Two-thirds (65.8%) reported having smoked crack cocaine. Approximately one-fourth of the women (28.1%) reported having had >20 sex partners in their lifetimes, and 41.1% reported having had commercial sex. One-third (35.7%) of the women began having sex before they were 15 years old. Nearly all of the women (87.9%) reported having smoked cigarettes.
In the discussion the authors said: We found that HIV was associated with multiple infections (e.g., >4 and .5 infections) even after we controlled for behavioral variables. This result suggests that, as has been shown for single infections, HIV may facilitate the transmission of other viruses, and other viruses may facilitate the transmission of HIV. For example, genital HSV-2 lesions can facilitate transmission of HIV or other sexually transmitted agents. Conversely, in HIV-infected persons, HSV-2 lesions occur more frequently and tend to last longer, thus increasing the chance that an individual will acquire or transmit additional infections.
IDU was a strong risk factor for both HBV and HCV and was associated, to a much lesser extent, with HHV-8 and CMV. Nearly all HCV was acquired via IDU; HCV seroprevalence was 89.7% among injection drug users, compared with 10.5% among noninjection drug users, and IDU was by far the strongest risk factor for HCV infection in multivariate analyses. Women in HERS who did not inject drugs may have acquired HCV sexually. The 10.5% HCV seroprevalence among noninjection drug users is much higher than that in the general population, which might be explained by higher numbers of sex partners and a higher prevalence of HCV infection in sex partners among women included in HERS.
Increasing rates of Sexual Transmission Among MSM in London & Risk Factors, Unsafe Sex Practices
"Evidence for Sexual Transmission of HCV in Recent Epidemic in HIV-infected Men in the UK"
Mark Danta*1, D Brown1, G Dusheiko1, O Pybus2, M Nelson3, M Fisher4, A Johnson1, C Sabin1, and S Bhagani6
1Royal Free and Univ Coll Med Sch, London, UK; 2Oxford Univ, UK; 3Chelsea and Westminster Hosp, London, UK; 4Brighton and Sussex Univ Hosp, Brighton, UK; and 6Royal Free Hosp, London, UK
The reported incidence of acute hepatitis C virus (HCV) among HIV-infected individuals has increased significantly in the United Kingdom and the rest of Europe. The aim of this study was to characterize the mode of acute HCV transmission in HIV-infected individuals from 3 U.K. clinics, using linked molecular and clinical epidemiological analysis.
Patients enrolled were diagnosed with acute HCV, defined by seroconversion of anti-HCV antibody within 6 months of a negative result or a positive HCV polymerase chain reaction (PCR), between October 2002 and August 2005. The E1/E2 region of the HCV genome from each patient's serum was amplified with real-time PCR and sequenced. Using PAUP software, phylogenetic trees were constructed from the amplified sequences, comparing them with unrelated E1/E2 sequences. A questionnaire-based case-control study was performed to determine transmission factors using HIV mono-infected controls from each clinic's database, matching for age, race, length of HIV infection, and HAART.
Results
They identified 111 HIV+ homosexual males (mean age 35 years, CD4 552 cells/mL, 65% on HAART) with acute HCV (HCV genotype 1, 88%, genotype 3a, 8%, genotype 4, 4%). Phylogenetic analysis of 91 E1/E2 sequences reveals multiple monophyletic clades signifying that several independent HCV lineages (clades) are co-circulating in this population. The largest clade involves 43 patients. Provisional population dynamic analysis of this clade suggests that there has been an increasing transmission rate over time.
Cases (n = 60) had more sexual partners than controls (n = 130, median number of partners 30 vs 10, p <0.001) in the preceding 12 months.
Factors identified more commonly in cases than controls were: unprotected receptive and insertive anal intercourse (p <0.001), mucosally traumatic practices including fisting (p <0.001) and use of sex toys (p <0.001), group sex (88% vs 64%, p <0.001), and sexual activity under the influence of drugs (92% vs 62%, p <0.001).
The authors concluded that high-risk and mucosally traumatic sexual factors are significantly associated with the recent transmission of HCV. The co-circulating HCV lineages identified by phylogenetic analysis belong to different subtypes and genotypes, indicating that the epidemic is not caused by viral genetic change, but rather patient factors such as sexual or drug behavior. These patient factors should be the focus of education-based public health interventions.
HIV infection and/or mucosal trauma caused by extreme sexual techniques and concurrent STD might facilitate sexual transmission of HCV in MSM
"Rise in HCV Incidence in HIV-infected Men Who Have Sex with Men in Amsterdam: Sexual Transmission of Difficult to Treat HCV Genotypes 1 and 4"
R Coutinho1 and Thijs van de Laar*2
1Hlth Svc, Amsterdam, The Netherlands and 2Amsterdam HCV Study Group, The Netherlands
Hepatitis C virus (HCV) is usually transmitted parenterally. However, recent reports suggest that HCV emerges as a sexually transmitted disease (STD) among HIV+ men who have sex with men (MSM).
The study retrospectively tested 1836 MSM participating in the Amsterdam Cohort Study (1985-2003) for HCV antibodies. Poisson regression analysis was used to evaluate temporal changes in HCV incidence. Additionally, during 2003 through 2005, they obtained serum samples of MSM who had been diagnosed with an acute HCV infection from hospitals in Amsterdam. HCV+ MSM were tested for HCV RNA. Part of the NS5B region of the HCV genome was amplified with RT-PCR, genotyped and sequenced. Phylogenetic trees were constructed from the sequences obtained comparing them with other unrelated NS5B sequences.
Results
HCV prevalence at cohort entry was 1.3%. The HCV incidence was 0.18/100 person-years in HIV-infected MSM and 0/100 person-years in MSM without HIV. After 2000, HCV incidence in HIV-infected MSM increased 10-fold compared with the 15 years before (0.08/100 person-years vs 0.87/100 person-years, p = 0.001). Combining cohort and hospital cases, 29 acute HCV infections were identified after 2000; 28 (97%) MSM were co-infected with HIV.
Observed HCV genotypes were: 4d (45%), 1a (38%), 3a (10%), and 1b (7%). Phylogenetic analysis (n = 24) showed 2 large clusters of respectively 10 (4d) and 5 (1a) MSM, and 2 smaller clusters (1a, 1b) of 2 MSM each. HCV lineages isolated from Amsterdam MSM did not resemble isolates of other Dutch risk groups. All 20 MSM interviewed denied injecting drug use; of 20 (90%), 18 reported either "fisting" (n = 10) or co-infections with mucosa-damaging STD (n = 13)—eg, lymphogranuloma venereum (LGV), syphilis, or HSV-2—within the period of HCV seroconversion.
The authors concluded that the incidence of HCV has significantly increased in HIV+ but not in HIV- MSM in Amsterdam. The high degree of clustering observed in phylogenetic analysis provides strong evidence for the introduction and sexual transmission of different co-circulating HCV lineages. HIV infection and/or mucosal trauma caused by extreme sexual techniques and concurrent STD might facilitate sexual transmission of HCV.
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