13th Conference on Retroviruses and Opportunistic Infections Denver, Colorado - February 5-8, 2006

Conf Retrovir Opportunistic Infect 2006 Feb 5-8;13:abstract no. 86

Mark Danta¹, D Brown¹, G Dusheiko¹, O Pybus², M Nelson³, M Fisher⁴, A Johnson¹, C Sabin¹, and S Bhagani^5
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 ⁵Royal Free Hosp, London, UK

BACKGROUND: 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.

METHODS: 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: We 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).

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 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.

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2006-02-05
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