Modeling of patient virus titers suggests that availability of a vaccine could reduce hepatitis C virus transmission among injecting drug users

被引:16
作者
Major, Marian [1 ]
Gutfraind, Alexander [2 ,3 ]
Shekhtman, Louis [2 ,4 ]
Cui, Qingwen [1 ]
Kachko, Alla [1 ]
Cotler, Scott J. [2 ]
Hajarizadeh, Behzad [5 ]
Sacks-Davis, Rachel [6 ,7 ]
Page, Kimberly [8 ]
Boodram, Basmattee [3 ]
Dahari, Harel [2 ]
机构
[1] US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Silver Spring, MD 20993 USA
[2] Loyola Univ Chicago, Dept Med, Program Expt & Theoret Modeling, Div Hepatol, Maywood, IL 60153 USA
[3] Univ Illinois, Sch Publ Hlth, Epidemiol & Biostat, Chicago, IL 60612 USA
[4] Bar Ilan Univ, Dept Phys, IL-52990 Ramat Gan, Israel
[5] Univ New South Wales, Kirby Inst, Sydney, NSW 2052, Australia
[6] Burnet Inst, Dis Eliminat Program, Melbourne, Vic 3004, Australia
[7] Univ Melbourne, Dept Med, Parkville, Vic 3010, Australia
[8] Univ New Mexico, Div Epidemiol Biostat & Prevent Med, Dept Internal Med, Hlth Sci Ctr, Albuquerque, NM 87131 USA
基金
英国医学研究理事会;
关键词
SPONTANEOUS CLEARANCE; DEAD-SPACE; VIRAL LOAD; HCV RNA; INFECTION; CHIMPANZEES; HIV; SYRINGES; PEOPLE; ASSAYS;
D O I
10.1126/scitranslmed.aao4496
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The major route of hepatitis C virus (HCV) transmission in the United States is injection drug use. We hypothesized that if an HCV vaccine were available, vaccination could affect HCV transmission among people who inject drugs by reducing HCV titers after viral exposure without necessarily achieving sterilizing immunity. To investigate this possibility, we developed a mathematical model to determine transmission probabilities relative to the HCV RNA titers of needle/syringe-sharing donors. We simulated sharing of two types of syringes fitted with needles that retain either large or small amounts of fluid after expulsion. Using previously published viral kinetics data from both naive subjects infected with HCV and reinfected individuals who had previously cleared an HCV infection, we estimated transmission risk between pairs of serodiscordant injecting drug users, accounting for syringe type, rinsing, and sharing frequency. We calculated that the risk of HCV transmission through syringe sharing increased similar to 10-fold as viral titers (log(10) IU/ml) increased similar to 25-fold. Cumulative analyses showed that, assuming sharing episodes every 7 days, the mean transmission risk over the first 6 months was >90% between two people sharing syringes when one had an HCV RNA titer >5 log(10) IU/ml. For those with preexisting immunity that rapidly controlled HCV, the cumulative risk decreased to 1 to 25% depending on HCV titer and syringe type. Our modeling approach demonstrates that, even with transient viral replication after exposure during injection drug use, HCV transmission among people sharing syringes could be reduced through vaccination if an HCV vaccine were available.
引用
收藏
页数:11
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