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EVIDENCE FOR SEXUAL TRANSMISSION OF HCV IN RECENT EPIDEMIC IN HIV-INFECTED MEN IN SOUTHEAST ENGLAND
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Mark Danta, David Brown, Centre for Hepatology, London, United Kingdom (Great Britain); Oliver Pybus, Department of Zoology, Oxford, United Kingdom (Great Britain); Mark Nelson, Department of HIV Medicine, London, United Kingdom (Great Britain); Martin Fisher, Department of HIV Medicine,
Brighton, United Kingdom (Great Britain); Caroline Sabin, Anne Johnson, Department of Primary Care and Population Sciences, London, United Kingdom (Great Britain); Geoffrey Dusheiko, Centre for Hepatology, London, United Kingdom (Great Britain); Sanjay Bhagani, Department of HIV Medicine, London, United Kingdom (Great Britain)
Aims: To characterise the mode of acute HCV transmission in HIV-infected individuals using linked molecular and clinical epidemiological analysis.
Methods: Patients enrolled were diagnosed with acute HCV, as defined by seroconversion to anti-HCV within six months of a negative result and/or a positive HCV RNA, between October 2002 and May 2005. The E1/E2 region of the HCV genome from each patient’s serum was amplified with RT-PCR and sequenced. Using PAUP* software, phylogenetic trees were constructed from the amplified sequences, comparing them with unrelated E1/E2 sequences. Past population dynamics of the largest independent HCV lineage (clade) were analysed using BEAST software.
A case-control study using a questionnaire instrument to determine transmission factors was performed using two HIV mono-infected controls for each case matching; sexuality, age, race, length of HIV infection and HAART. Mann-Whitney U and Chi-squared tests were used to compare the characteristics of
the cases (n=37) and controls (n=78).
Results:
100 HIV-positive homosexual males (mean age 35 yrs, CD4 552 cells/mcl, 65% on HAART) with acute HCV (HCV genotype 1: 75%, genotype 3a: 17%, genotype 4: 8%) have been identified.
Phylogenetic analysis of 80 E1/E2 sequences reveals multiple monophyletic clades signifying that several independent HCV lineages are co-circulating
in this population. The largest clade involves 31 patients.
Provisional population dynamic analysis of this clade suggests that there has been an increase in the transmission of HCV since the late 1990’s, after the introduction of HAART.
Cases had more sexual partners than controls (median number of partners 30 vs 10, p<0.001) in the preceding 12 months.
Preliminary factors identified more commonly in cases (n=37) vs controls (n=78) are:
--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 (87% vs 52.3%, p<0.01), and
--sexual activity under the influence of drugs (100% vs 64%,
p<0.003).
Conclusions: 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 attributable to viral genetic change, but
rather patient factors such as sexual or drug behaviour. This is supported by the population dynamic analysis. These patient factors should be the focus of education-based public health interventions.
ED NOTE from Jules Levin: the study did not examine prevalence of STDs or syphilis. The presence of STDs could have been a contributing factor to HCV transmission.
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