Reinfection and Risk Behaviors After Treatment of Hepatitis C Virus Infection in Persons Receiving Opioid Agonist Therapy

Grebely, Jason; Dore, Gregory J.; Altice, Frederick L.; Conway, Brian; Litwin, Alain H.; Norton, Brianna L.; Dalgård, Olav; Gane, Edward; Shibolet, Oren; Nahass, Ronald; Luetkemeyer, Anne F; Peng, Cheng Yuan; Iser, David; Gendrano, Isaias Noel; Kelly, Michelle M.; Hwang, Peggy; Asante‐Appiah, Ernest; Haber, Barbara; Barr, Eliav; Robertson, Michael; Platt, Heather

doi:10.7326/m21-4119

Cited by 12 publications

(7 citation statements)

References 38 publications

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“…In this international cohort composed predominantly of GBM with HIV from high-income countries, high reinfection incidence was observed among people treated for recent HCV infection, two to three times greater than contemporary reinfection estimates among at-risk populations treated for chronic HCV [8,9,[15][16][17]. Reinfection was associated with a previous diagnosis of HCV reinfection, injection drug use posttreatment, condomless anal intercourse with casual male partners and geographic region.…”

Section: Discussionmentioning

confidence: 82%

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Reinfection incidence and risk among people treated for recent hepatitis C virus infection: the react study

Martinello

Carson

Valk

et al. 2023

Aids

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Objective: Reinfection poses a challenge to HCV elimination. This analysis assessed incidence of, and factors associated with reinfection among people treated for recent HCV (duration of infection <12 months). Methods: Participants treated for recent HCV (primary infection or reinfection) in an international randomised trial were followed at three-monthly intervals for up to two years to assess for reinfection. Reinfection incidence was calculated using person-time of observation. Factors associated with HCV reinfection were assessed using Cox proportional hazards regression analysis. Results: Of 222 participants treated for recent HCV, 196 (62% primary infection, 38% reinfection) were included in the cohort at risk for reinfection, of whom 87% identified as gay or bisexual men, 71% had HIV, and 20% injected drugs in the month prior to enrolment. During 198 person-years of follow-up, 28 cases of HCV reinfection were identified among 27 participants, for an incidence of 14.2 per 100 person-years (95%CI 9.8, 20.5). Reinfection was associated with prior HCV reinfection (aHR 2.42; 95%CI 1.08, 5.38), injection drug use post-treatment (aHR 2.53; 95%CI 1.14, 5.59), condomless anal intercourse with casual male partners (aHR 3.32; 95%CI 1.14, 9.65) and geographic region (United Kingdom, aHR 0·21; 95% CI 0.06, 0.75). Among gay and bisexual men, reinfection was also associated with sexualised drug use involving injecting post-treatment (aHR 2.97; 95%CI 1.10, 8.02). Conclusion: High reinfection incidence following treatment for recent HCV among people with ongoing sexual and drug use risk behaviour highlights the need for post-treatment surveillance, rapid retreatment of reinfection, and targeted harm reduction strategies. Clinical trial registration: clinicaltrials.gov Identifier NCT02625909 Funding: National Institutes of Health (R01DA040506). Study medication - Gilead Sciences Inc.

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Section: Discussionmentioning

confidence: 82%

“…Onethird reported needle/syringe sharing, higher than other studies of reinfection following recent (22%) and chronic (6%) infection among PWID [14,19]. For PWID, access to harm reduction interventions known to reduce risk is essential [17,20]. However, different PWID populations require nuanced approaches.…”

Section: Discussionmentioning

confidence: 98%

Reinfection incidence and risk among people treated for recent hepatitis C virus infection: the react study

Martinello

Carson

Valk

et al. 2023

Aids

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“…In a systematic review, the rate of HCV reinfection after successful DAA therapy among people with recent drug use was reported to be 5.9 per 100 person‐years 23 . A recent study showed a reinfection rate of 1.7 per 100 person‐years among people receiving opioid agonist therapy (OAT) for at least 3 months and who were at least 80% adherent to OAT appointments 24 . These data showed that the reinfection rate was lower if patients continue to engage in addiction treatment therapies.…”

Section: Discussionmentioning

confidence: 99%

“…for at least 3 months and who were at least 80% adherent to OAT appointments. 24 These data showed that the reinfection rate was lower if patients continue to engage in addiction treatment therapies. Furthermore, the cure for HCV infection should have a positive effect on PWIDs and PWUDs.…”

Section: Measures In the United States And Challenges In Linkage To C...mentioning

confidence: 97%

A single site study to investigate the current prevalence of anti‐hepatitis C virus antibody among substance use disorder patients in Hiroshima—Insufficient testing and diagnosis

Kagaya¹,

Nagaoki

Shimura

et al. 2023

Neuropsychopharm Rep

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AimsHepatitis C virus (HCV) infection among drug users presents an important public health problem; however, little recognition and few approaches to address this issue in Japan. This study was conducted to investigate the current disease status by assessing anti‐HCV antibody (Ab) seroprevalence among people who inject drugs (PWIDs) and people who use drugs (PWUDs) in Hiroshima, Japan.MethodsThis study was a psychiatric single‐site chart review in patients with drug abuse problems in the Hiroshima region. The primary outcome was anti‐HCV Ab prevalence among PWIDs who underwent anti‐HCV Ab testing. The secondary outcomes included the prevalence of anti‐HCV Ab among PWUDs who underwent anti‐HCV Ab testing and the proportion of patients who underwent anti‐HCV Ab examination.ResultsA total of 222 PWUD patients were enrolled. Among these, 16 patients (7.2%) had records of injection drug use (PWIDs). Eleven (68.8%) of the 16 PWIDs received anti‐HCV Ab tests, and 4 (36.4%, 4/11) were anti‐HCV Ab‐positive. Among 222 PWUDs, 126 (56.8%) patients received anti‐HCV Ab tests, and 57 of these patients (45.2%, 57/126) were anti‐HCV Ab‐positive.ConclusionThe prevalence of anti‐HCV Ab among PWIDs and PWUDs who visited the study site was higher than the general population, which was 2.2% among hospitalized patients between May 2018 and November 2019. Considering the World Health Organization's (WHO) elimination goal and recent advances in HCV treatment, patients with drug abuse experience should be encouraged to take HCV tests and consult hepatologists for further investigations and treatment if they are positive for anti‐HCV Ab.

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“…Hepatitis C virus (HCV) infection represents an ideal model to study this question with two dichotomous outcomes where approximately 30% of acutely infected individuals resolve spontaneously while the rest develop chronic infection. Despite the resolution of primary HCV infection, people who inject drugs (PWID) remain at high risk of HCV exposure and reinfection (4)(5)(6)(7)(8), thus representing a natural experimental rechallenge framework to study memory immune responses against human viral infection. Spontaneous resolution of primary HCV is associated with both Tcell and antibody responses.…”

Section: Introductionmentioning

confidence: 99%

Coordinated expansion of memory T follicular helper and B cells mediates spontaneous clearance of HCV reinfection

Eisa,

Gomez-Escobar,

Bédard

et al. 2024

Front. Immunol.

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IntroductionFollicular helper T cells are essential for helping in the maturation of B cells and the production of neutralizing antibodies (NAbs) during primary viral infections. However, their role during recall responses is unclear. Here, we used hepatitis C virus (HCV) reinfection in humans as a model to study the recall collaborative interaction between circulating CD4 T follicular helper cells (cTfh) and memory B cells (MBCs) leading to the generation of NAbs.MethodsWe evaluated this interaction longitudinally in subjects who have spontaneously resolved primary HCV infection during a subsequent reinfection episode that resulted in either another spontaneous resolution (SR/SR, n = 14) or chronic infection (SR/CI, n = 8).ResultsBoth groups exhibited virus-specific memory T cells that expanded upon reinfection. However, early expansion of activated cTfh (CD4+CXCR5+PD-1+ICOS+FoxP3−) occurred in SR/SR only. The frequency of activated cTfh negatively correlated with time post-infection. Concomitantly, NAbs and HCV-specific MBCs (CD19+CD27+IgM−E2-Tet+) peaked during the early acute phase in SR/SR but not in SR/CI. Finally, the frequency of the activated cTfh1 (CXCR3+CCR6−) subset correlated with the neutralization breadth and potency of NAbs.ConclusionThese results underscore a key role for early activation of cTfh1 cells in helping antigen-specific B cells to produce NAbs that mediate the clearance of HCV reinfection.

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Reinfection and Risk Behaviors After Treatment of Hepatitis C Virus Infection in Persons Receiving Opioid Agonist Therapy

Cited by 12 publications

References 38 publications

Reinfection incidence and risk among people treated for recent hepatitis C virus infection: the react study

Reinfection incidence and risk among people treated for recent hepatitis C virus infection: the react study

A single site study to investigate the current prevalence of anti‐hepatitis C virus antibody among substance use disorder patients in Hiroshima—Insufficient testing and diagnosis

Coordinated expansion of memory T follicular helper and B cells mediates spontaneous clearance of HCV reinfection

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