TY - JOUR
T1 - Sex Discrepancies in the Protective Effect of Opioid Agonist Therapy on Incident Hepatitis C Infection
AU - Geddes, Louise
AU - Iversen, Jenny
AU - Wand, Handan
AU - Esmaeili, Aryan
AU - Tsui, Judith
AU - Hellard, Margaret
AU - Dore, Gregory
AU - Grebely, Jason
AU - Dietze, Paul
AU - Bruneau, Julie
AU - Prins, Maria
AU - Morris, Megan D.
AU - Shoukry, Naglaa H.
AU - Lloyd, Andrew R.
AU - Kim, Arthur Y.
AU - Lauer, Georg
AU - Cox, Andrea L.
AU - Page, Kimberly
AU - Maher, Lisa
N1 - Funding Information:
Potential conflicts of interest. J. B., P. D., and M. H. have received funding from Gilead Sciences for work on HCV treatment. P. D. has received funding from Reckitt Benckiser, the Ramsay Foundation, and Indivior. J. G. is a consultant/advisor and reports grants from AbbVie and Cepheid, and grants and personal fees from Gilead Sciences and Merck. M. H. has received funding from AbbVie and Bristol-Meyers Squibb for investigator-initiated HCV research. G. D. is a consultant/advisor and has received research grants from AbbVie, Bristol-Myers Squibb, Cepheid, Gilead, Merck, Janssen, and Roche. J. B. has received personal fees from Gilead Sciences and Merck Canada (Merke Sharp Dohme). A. L. has received grants from Gilead Sciences and AbbVie. All other authors report no potential conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
Funding Information:
InC3 was funded by the National Institute on Drug Abuse (NIDA) (grant number R01DA031056). Research support for the InC3 cohorts includes the following: Netherlands National Institute for Public Health and the Environment (support to the ACS); National Institutes of Health (NIH) to BBAASH (grant number U19 AI088791); the National Institute of Allergy and Infectious Diseases (NIH) to BAHSTION (grant number U19 U19 AI066345); the NIDA to the ATAHC (grant number RO1 DA 15999-01); the National Health and Medical Research Council (Australia) (NHMRC) to HITS-p (project number 222887, partnership number 1016351, program numbers 510488 and 1053206); the University of New South Wales Hepatitis C Vaccine Initiative and NHMRC to HITS-c (project grant number 630483); the NHMRC (project grant numbers 331312 and 545891); the Victorian Operational Infrastructure Support Programme (Department of Health, Victoria, Australia) to Networks/SuperMIX; the Canadian Institutes of Health Research to HepCo (grant numbers MOP-103138 and MOP-19106468); Reseau SIDA Maladies Infectieuses, Rese ctieuses, Fonds de la Recherche du Quebec-Sante supports the HepCo cohort (grant number Octroi 52905); the NHMRC to HCVC (project grant number 991357); and the NIH to UFO (grant number R01 DA016017). J. I., M. H., P. D., A. L., G. D., J. G., and L. M. receive fellowship support from the Australian NHMRC. N. S. receives support from the Fonds de la Recherche du Quebec-Sante, Canada. In addition to grant support for the InC3 research, K. P. receives support from The Australian Government Research Training Program Scholarship is a program which funds PhDs in Australia (grant numbers 3R01 DA016017, 1ULTR001449, and U54GM104944). L. G. is supported through an Australian Government Research Training Program Scholarship. P. D. received grant funding from the Colonial Foundation Trust.
Funding Information:
Financial support. InC3 was funded by the National Institute on Drug Abuse (NIDA) (grant number R01DA031056). Research support for the InC3 cohorts includes the following: Netherlands National Institute for Public Health and the Environment (support to the ACS); National Institutes of Health (NIH) to BBAASH (grant number U19 AI088791); the National Institute of Allergy and Infectious Diseases (NIH) to BAHSTION (grant number U19 U19 AI066345); the NIDA to the ATAHC (grant number RO1 DA 15999-01); the National Health and Medical Research Council (Australia) (NHMRC) to HITS-p (project number 222887, partnership number 1016351, program numbers 510488 and 1053206); the University of New South Wales Hepatitis C Vaccine Initiative and NHMRC to HITS-c (project grant number 630483); the NHMRC (project grant numbers 331312 and 545891); the Victorian Operational Infrastructure Support Programme (Department of Health, Victoria, Australia) to Networks/SuperMIX; the Canadian Institutes of Health Research to HepCo (grant numbers MOP-103138 and MOP-19106468); Réseau SIDA Maladies Infectieuses, Rése ctieuses, Fonds de la Recherche du Québec-Santé supports the HepCo cohort (grant number Octroi 52905); the NHMRC to HCVC (project grant number 991357); and the NIH to UFO (grant number R01 DA016017). J. I., M. H., P. D., A. L., G. D., J. G., and L. M. receive fellowship support from the Australian NHMRC. N. S. receives support from the Fonds de la Recherche du Québec-Santé, Canada. In addition to grant support for the InC3 research, K. P. receives support from The Australian Government Research Training Program Scholarship is a program which funds PhDs in Australia (grant numbers 3R01 DA016017, 1ULTR001449, and U54GM104944). L. G. is supported through an Australian Government Research Training Program Scholarship. P. D. received grant funding from the Colonial Foundation Trust.
Publisher Copyright:
© 2019 The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved.
PY - 2020/1/1
Y1 - 2020/1/1
N2 - Background: While opioid agonist therapy (OAT) reduces the risk of hepatitis C virus (HCV) acquisition among people who inject drugs (PWID), protective effects may be attenuated in females. We used pooled data from an international collaboration of prospective cohorts to assess sex disparities in HCV incidence among PWID exposed to OAT. Methods: Independent predictors of HCV infection were identified using Cox regression models with random effects after accounting for the clustering effect of study sites. Unadjusted and adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) are presented in sex-specific analyses. Results: Among 701 participants exposed to OAT, HCV incidence was 16.5/100 person-years of observation (PYO) (95% CI, 13.1-20.7) in females and 7.6/100 PYO (95% CI, 6.0-9.5) in males (female:male adjusted HR [aHR], 1.80 [95% CI, 1.37-2.22]; P <. 001). Factors associated with HCV acquisition among females exposed to OAT included nonwhite race (aHR, 1.79 [95% CI, 1.25-2.56]; P =. 001), unstable housing (aHR, 4.00 [95% CI, 3.62-4.41]; P <. 001), daily or more frequent injection (aHR, 1.45 [95% CI, 1.01-2.08]; P =. 042), and receptive syringe sharing (aHR, 1.43 [95% CI, 1.33-1.53]; P <. 001). Conclusions: Female PWID exposed to OAT are twice as likely as their male counterparts to acquire HCV. While there is a need for better understanding of sex differences in immune function and opioid pharmacokinetic and pharmacodynamic parameters, structural and behavioral interventions that target women are required to bolster the efficacy of OAT in preventing HCV transmission.
AB - Background: While opioid agonist therapy (OAT) reduces the risk of hepatitis C virus (HCV) acquisition among people who inject drugs (PWID), protective effects may be attenuated in females. We used pooled data from an international collaboration of prospective cohorts to assess sex disparities in HCV incidence among PWID exposed to OAT. Methods: Independent predictors of HCV infection were identified using Cox regression models with random effects after accounting for the clustering effect of study sites. Unadjusted and adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) are presented in sex-specific analyses. Results: Among 701 participants exposed to OAT, HCV incidence was 16.5/100 person-years of observation (PYO) (95% CI, 13.1-20.7) in females and 7.6/100 PYO (95% CI, 6.0-9.5) in males (female:male adjusted HR [aHR], 1.80 [95% CI, 1.37-2.22]; P <. 001). Factors associated with HCV acquisition among females exposed to OAT included nonwhite race (aHR, 1.79 [95% CI, 1.25-2.56]; P =. 001), unstable housing (aHR, 4.00 [95% CI, 3.62-4.41]; P <. 001), daily or more frequent injection (aHR, 1.45 [95% CI, 1.01-2.08]; P =. 042), and receptive syringe sharing (aHR, 1.43 [95% CI, 1.33-1.53]; P <. 001). Conclusions: Female PWID exposed to OAT are twice as likely as their male counterparts to acquire HCV. While there is a need for better understanding of sex differences in immune function and opioid pharmacokinetic and pharmacodynamic parameters, structural and behavioral interventions that target women are required to bolster the efficacy of OAT in preventing HCV transmission.
KW - harm reduction
KW - opioid agonist therapy
KW - people who inject drugs
KW - sex; hepatitis C virus
UR - http://www.scopus.com/inward/record.url?scp=85076537181&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85076537181&partnerID=8YFLogxK
U2 - 10.1093/cid/ciz162
DO - 10.1093/cid/ciz162
M3 - Article
C2 - 30816419
AN - SCOPUS:85076537181
SN - 1058-4838
VL - 70
SP - 123
EP - 131
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 1
ER -