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HCV Sexual Transmission --MSM & Heterosexual
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Reported by Jules Levin
Simultaneously, at both the EACS HIV conference in Warsaw and at the AASLD liver conference in Boston researchers reported studies about the risk for sexual transmission of HCV among men who have sex with men. Additionally, at AASLD researchers reported on the presence of HCV in the genital secretions of women infected with both HIV and HCV. The authors of this study reported that women with HCV in genital secretions also had vaginal infections or lacerations. The authors raised concerns about sexual transmission of HCV and from mother to newborn.
The studies raise an interesting issue about the possibility of identifying acute HCV infection in people identified with acute HIV infection. If at-risk individuals are tested and identified with acute HIV, they should also be tested for HCV. Several studies show acute HCV can be treated with significantly higher rates of viral clearance than in chronically infected HCV. This appears to be in contrast with treating acute HIV. HIV therapy is lifetime, cannot be eradicated with current drugs, and studies of treating acute HIV have recently reported questions about initiating HAART for acute HIV. Viral failure can occur and this may affect subsequent therapy for HIV and the long term course of successfully treating HIV. However, since HCV therapy is short term, for 6 or 12 months, and HCV can be eradicated, identification and treatment for acute HCV appears to be a strategy worth pursuing.
The studies reported on the risk for sexual transmission among MSM are the latest to be presented. These concerns were first reported at the Retrovirus Conference in 2001 by researchers from British Vancouver. NATAP reported on this study and has been following this hot topic ever since. Here is a link to the original NATAP Retrovirus Report of this study:
Risky Sex Practices That May Increase Risk for Getting HCV Among Men Who Have Sex With Men http://www.natap.org/2001/8thcroi/riskysex022601.htm
Craib and colleagues looked at stored blood samples to determine HCV prevalence & identify risk factors for HCV in a group of sexually active HIV+ and HIV- MSM in British Vancouver, Canada. HIV+ men were more likely to have HCV and the risk factors for having HCV were: >20 sex partners in the last year; oral-anal contact; insertive fisting; receptive anal intercourse; injection drug use; illegal drug use. 50% of the HCV+ men reported never using injection drugs, and among them insertive fisting and oral-anal contact were significant risk factors for being HCV+. The authors concluded that “specific sex practices that might include the exchange of blood” may increase the risk for acquiring HCV.
Since the initial presentation by the researchers in British Columbia several reports and studies presented at scientific conferences have emerged regarding increased risk for sexual transmission among MSM. Simultaneously, there have been several published studies finding increased risk for heterosexual sexual transmission of HCV when certain circumstances are present: anal sex; sex during menstruation; when STDS and HIV are present; herpes; open sores; multiple sex partners.
Here are the latest reports from EACS in Warsaw and AASLD in Boston, conferences simultaneously held.
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Acute HCV Infection Among MSM in London, UK
Mark Danta and colleagues from the Royal Free Hospital, London, UK reported on a study at the 2003 AASLD liver conference just completed in Boston, MA (October 29, 2003).
The objective of the study was to characterize the infection and transmission of acute HCV in a cohort of HIV positive homosexual males in London. A group of men with (n=23) acute HCV infection with HIV positive has been identified using paired HCV antibody serology (EIA-3) and HCV PCR by RT-PCR (TMA, Versant) between February 2001 and April 2003.
Eradication of HCV was defined by subsequent HCV PCR negativity. Genotype was determined by Lipa (Genprobe). Detailed demographic, clinical and serological data were collected. Clinical and molecular epidemiological analysis has been performed to elucidate the source of acute HCV transmission. Relatedness of the HCV isolates was examined by sequencing the hypervariable region (HVR1) and NS5B regions of the HCV genome with construction of phylogenetic trees.
Patients were all Caucasian homosexual males (mean age 35 years). HCV was predominantly genotype 1 (one 3A and 4). The mean peak ALT was 674 U/l and initial mean HCV viral load was 1.3 x106 IU/ml. At diagnosis the mean CD 4 count was 600 cells and the HIV viral load was 1.6 x105 copies/ml (nine had undetectable levels). Thirteen patients were on HAART.
The risk factors for infection were: unprotected sexual intercourse was a universal risk factor, with group sex and fisting in (70%); intranasal drug use in 15 (65%), injected drugs in 4 (17%).
Supporting an hypothesis of sexual transmission, ten (43%) had a documented STD (7 syphilis and 1 gonorrhoea), including 2 patients with acute HIV seroconversion. To date five isolates have been sequenced and three appear related by phylogenetic analysis, suggesting a common source.
The four patients who eradicated the HCV spontaneously had significantly higher CD4 counts (810 vs 556, p<0.05). There was no correlation with peak ALT or HIV viral load. Nine patients are now on pegylated interferon and ribavirin. The authors concluded that this cohort provides insight into the natural history of HCV in HIV. A higher CD4 count appears to predict HCV eradication. Clinical and molecular evidence suggests both sexual and intranasal transmission of HCV among homosexual men.
At the EACS HIV Conference being held in Warsaw, Poland simulataneous to AASLD London researchers reported similar information.
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Barebacking the sole common risk factor in London's sexually transmitted hepatitis C epidemic - www.aidsmap.com
Being the passive partner during unprotected anal intercourse is emerging as the main sexual practice associated with gay HIV-positive men becoming co-infected with hepatitis C (HCV), according to a presentation in Warsaw today from Professor Brian Gazzard of the Chelsea & Westminster Hospital, London's largest HIV clinic.
In the past 21 months, 44 new, acute HCV infections have been diagnosed at the C&W, all of whom have been in gay HIV-positive men. "It is clear there is an epidemic going on within the London gay community of acute hepatitis C infection," Professor Gazzard told the conference, "and this is also being seen in a number of other units across London." The Royal Free and Mortimer Market Centre presented data earlier this year about their own experiences with the epidemic.
Modes of transmission have not been identified in four co-infected gay men, and another four also injected drugs (two of whom also had unprotected anal intercourse).
It was just over a year ago that AIDS Treatment Update published the first reports about this new sexually transmitted epidemic, and since then aidsmap has reported on its developments. One of the major issues is exactly how and why HCV is being sexually transmitted amongst gay HIV-positive in London. As well as barebacking, associations with fisting, sharing drug-snorting paraphernalia, and particularly syphilis have been made, but according to Professor Gazzard receptive unprotected anal intercourse was the single common factor amongst the 44 out of the total of 50 gay men seen at their HIV/HCV co-infection clinic since it began in January 1997.
"They all had passive anal sex," he told aidsmap, "but many of them were also fisting. We did ask about [snorting drugs] and we didn't find any association, so I don't think that was a risk factor." The C&W also found that around 40% had been diagnosed with syphilis in the year prior to HCV seroconversion.
At the moment, it is not known whether it is other acutely or chronically co-infected HCV/HIV-positive men who are most likely to transmit HCV to their sexual partners, but extremely high HCV viral loads are seen during acute infection and just like HIV, HCV is more likely to be transmitted when viral loads are high, and possibly in the presence of an STI, like syphilis. The next step will be to do "DNA fingerprinting, to see if it comes from a common source or many difference sources," Professor Gazzard said. "The suspicion is that it may well come from a common source."
The C&W has learned lessons about identifying and treating new cases of HCV co-infection from its past experiences, and now does routine liver function tests every three months on all of their HIV-positive patients. If they are abnormal, they are then screened for HCV antibody and HCV PCR (viral load. Thirty-nine of the 50 co-infection cases reported so far in the epidemic were picked up in this way, another three told their doctors they had had barebacked with a known HCV-positive sexual partner, four presented at the clinic with jaundice, and the rest were screened for HCV during seroconversion for HIV antibodies.
Although treatment with the 'gold standard' of pegylated interferon/ribavirin is standard practice at the C&W, they now wait 12 weeks to see if the HCV co-infection spontaneously clears, since so far 12 out of the 22 patients who did not take any treatment spontaneously converted to HCV PCR negative within that time. "We were surprised by the relatively high rate of spontaneous conversion to PCR negative," said Professor Gazzard, "since it is not that different to what it is seen in HIV-negative patients."
Factors associated with spontaneously converting to HCV PCR negative including having a CD4 count above 500 (70% vs 30%) and higher peak ALT levels at diagnosis, indicating a greater hepatic inflammatory response.
Of the 24 individuals who received anti-HCV therapy, 15 finished treatment, and nine are continuing. One received interferon/ribavirin, one pegylated interferon alone, and the rest pegylated interferon/ribavirin. 10 out of the 15 have been successfully treated to PCR negativity with a follow-up of between 1-8 months. Of the five that failed treatment, one was due to toxicity, and four due to lack of response.
However, of the nine individuals presently receiving treatment, four have a poor anti-HCV response. Putting a positive spin on things, Professor Gazzard reported that they had found that the short-term success rate of treatment of acute HCV co-infection "was close to 60%." Reference Nelson M. et al. Increasing Incidence Of Acute Hepatitis C In HIV Positive Men Secondary To Sexual Transmission, Epidemiology And Treatment Ninth European AIDS Conference, Warsaw, abstract F12/3, 2003.
At AASLD researchers reported on finding HCV in female genital secretions of women with HIV. The women with HCV in genital secretions had vaginal infections and lacerations.
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HCV Presence in Genital Secretions in HIV/HCV Coinfected Women
Jorge Rakela and colleagues from the Mayo Clinic Clinic, Scottsdale, AZ and the University of Southern California, Los Angeles, CA reported these study findings.
Sexual transmission of HCV occurs at a low level and seems to be more prevalent among women co-infected with HIV and HCV. Although some studies show increased risk for transmission when certain circumstances are present: anal sex, multiple sex partners, sex during menstruation, when STDS, HIV and herpes are present, when open sores are present, and when risky behavior suching as fisting occurs which may lead to blood-to-blood contact. Mother to infant transmission of HCV is also more common in the setting of HIV/HCV co-infection and the mechanism is unclear. Genital secretions are rarely studied because of difficulties in obtaining such specimens.
The aim of the study is to define prevalence of HCV in genital secretions among women infected with HCV. The authors have studied 75 anti-HCV positive women enrolled in the Women's Interagency HIV-1 Study (WHIS) at the Los Angeles site. They studied plasma and cervical lavage (CVL) specimens, and determined anti-HCV in plasma, HCV-RNA presence and titer in plasma and CVL. They further characterized amplified viral sequences by single strand conformational polymorphism (SSCP), cloning and sequencing.
Sixty-two of 75 women (83%) who were anti-HCV positive were also HIV positive. CVL from 18 of 62 women (28%) who were co-infected with HIV was HCV-RNA positive; none of CVL from 13 women who were anti-HCV positive only was HCV-RNA positive (p=. 03, Fisher's exact test). Sixteen CVL specimens had HCV < 8,000 copies/ml. Two CVL specimens had HCV RNA of 8,360 and 39,667 copies/ml. The mean HCV viral load in CVL was 1.52x103 copies/ml.
A multivariate analysis that included CD4 counts, CD3 counts, HIV RNA in plasma, HIV RNA in CVL, and HCV RNA in plasma, showed that the only independent predictors of HCV RNA in CVL were HCV viremia in plasma (p=0.02) and HIV viremia in CVL (p=0.03). We studied in detail plasma and CVL HCV quasispecies from 9 women. HCV-RNA was detected in both plasma and CVL in 5 of 9 women. HCV-RNA negative strand was found in CVL in one. In 4 of 5 women, SSCP, cloning and sequencing demonstrated that HCV strain present in CVL was unique to that compartment.
The authors said that all the women who acquired HCV from sex partners had vaginal infections or lacerations.
The authors concluded: 1) HCV-RNA in CVL is more likely to be present in HIV/HCV co-infected women; this may provide substrate to increased likelihood of HCV transmission to their respective sexual contacts and may also provide an explanation for the increased likelihood of HCV transmission to their infants 2) The presence of HCV-RNA in CVL was associated with HIV-RNA in the same compartment; this suggests a local interaction between both viruses that needs further analysis. 3) We found evidence of HCV compartmentalization in CVL; this finding supports the concept of extrahepatic HCV replication and may be consequential for sexual and mother to infant transmission of HCV. Supported by NIH grants DA13760 and RO1 AI52065. |
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