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HIV Transmission Bottleneck Offers Clue to HCV Epidemic in HIV+ MSM
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CROI 2014, March 3-6, 2014, Boston
Mark Mascolini
HIV-positive men who have sex with men (MSM) who had a broad HIV transmission bottleneck were more likely to become infected with hepatitis C virus (HCV) during follow-up, according to results of a 558-man analysis in the Swiss HIV Cohort Study (SHCS) [1]. The finding supports the hypothesis that frequent risky sex explains the recent spread of HCV among MSM because high-risk sex and an impaired mucosal barrier would contribute to a broad transmission bottleneck.
Epidemiologic work in Western Europe, Australia, and the United States tracks a growing HCV epidemic in MSM, including MSM with HIV. The reasons for these HCV outbreaks remain unclear, but frequent condom-free sex between men seems a likely suspect. To learn more about HCV transmission in HIV-positive MSM, SHCS investigators analyzed HCV incidence and transmission bottlenecks in MSM enrolled in the cohort.
A transmission bottleneck is a term that describes how many genetically distinct viruses can be transmitted during one sex act. A wide bottleneck allows transmission of several genetically distinct viruses, while a narrow bottleneck allows transmission of one or few genetically distinct viruses. Research links high-risk sexual behavior with wide HIV transmission bottlenecks [2,3]. SHCS investigators hypothesized that HCV incidence would be higher in MSM with a broad HIV transmission bottleneck. To test this hypothesis, they assessed the association between (1) viral diversity in recently HIV-infected antiretroviral-naive MSM and (2) HCV incidence.
The analysis included 558 MSM in the SHCS with recent HIV infection and an accurately estimated HIV seroconversion date after 1998. All men had an HIV genotypic resistance test within 1 year of estimated seroconversion, and all had an initially negative HCV test and at least one subsequent HCV test. (HCV-negative people in the SHCS get tested for HCV at least every 2 years.) The researchers defined a narrow HIV transmission bottleneck as one in which the fraction of ambiguous nucleotides in genotyping samples lies below below 0.5% [4]. A broad HIV transmission bottleneck meant the fraction of ambiguous nucleotides was 0.5% or higher.
Total HCV incidence stood at 8.9 per 1000 person-years, meaning about 9 of every 1000 men became infected with HCV every year. The bottleneck analysis showed that 428 men had a narrow bottleneck and 130 had a broad bottleneck. Among the 130 men with a broad bottleneck, 26 (20%) became infected with HCV during follow-up. HCV incidence was 12 per 656 person-years in men with a broad bottleneck and 14 per 2279 person-years in men with a narrow bottleneck.
Cox proportional hazards analysis determined that men with a broad transmission bottleneck versus a narrow bottleneck had a tripled risk of incident HCV infection (hazard ratio [HR] 3.02, 95% confidence interval [CI] 1.40 to 6.55). When the researchers further adjusted the analysis for age at HIV seroconversion, year of HIV seroconversion, and lab performing the genotypic resistance test, men with a broad bottleneck had an even higher risk of HCV infection (HR 3.17, 95% CI 1.45 to 6.91).
The SHCS team concluded that HIV-positive MSM with a broad HIV transmission bottleneck had a highly increased incidence of HCV infection. They believe this result supports the hypothesis that high-risk sexual behavior indicated by mucosal breaches plays a key role in sexual transmission of HCV.
References
1. Kouyos RD, Rauch A, Braun D, et al. Higher risk of sexually acquired HCV coinfection in MSM with wide HIV transmission bottleneck. CROI 2014. Conference on Retroviruses and Opportunistic Infections. March 3-6, 2014. Boston. Abstract 675.
2. Keele BF, Giorgi EE, Salazar-Gonzalez JF, et al. Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection. Proc Natl Acad Sci USA. 2008;105:7552-7557.
3. Rieder P, Joos B, Scherrer AU, et al. Characterization of human immunodeficiency virus type 1 (HIV-1) diversity and tropism in 145 patients with primary HIV-1 infection. Clin Infect Dis. 2011;53:1271-1279.
4. Kouyos RD, Wyl von V, Yerly S, et al. Ambiguous nucleotide calls from population-based sequencing of HIV-1 are a marker for viral diversity and the age of infection. Clin Infect Dis. 2011;52:532-539.
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