Tenofovir Disoproxil Fumarate and Tenofovir Alafenamide Interruption in Hepatitis B Virus/HIV Co-Infected Individuals in the USA: Monitoring Practices and Incidence of Hepatitis B Virus Reactivation or Hepatitis Flare - European Medical Journal

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Tenofovir Disoproxil Fumarate and Tenofovir Alafenamide Interruption in Hepatitis B Virus/HIV Co-Infected Individuals in the USA: Monitoring Practices and Incidence of Hepatitis B Virus Reactivation or Hepatitis Flare

2 Mins
Hepatology
Authors:
Douglas T. Dieterich,1 *Laurence Brunet,2 Ricky K. Hsu,3 Karam Mounzer,4 Gerald Pierone,5 Michael B. Wohlfeiler,6 Jennifer S. Fusco,2 Megan S. Dunbar,7 Joshua Gruber,7 Leland J. Yee,8 Catherine Frenette,9 Gregory P. Fusc2
  • 1. Institute for Liver Medicine, Mount Sinai Health System, Icahn School of Medicine at Mount Sinai, New York, USA
  • 2. Epividian, Raleigh, North Carolina, USA
  • 3. AIDS Healthcare Foundation, NYU Langone Medical Center, New York, USA
  • 4. Philadelphia FIGHT, Pennsylvania, USA
  • 5. Whole Family Health Center, Vero Beach, Florida, USA
  • 6. AIDS Healthcare Foundation, Miami, Florida, USA
  • 7. HIV Global Medical Affairs, Gilead Sciences, Foster City, California, USA
  • 8. Gilead Sciences, Foster City, California, USA
  • 9. Global Medical Affairs, Liver Diseases, Gilead Sciences, Foster City, California, USA
*Correspondence to [email protected]
Disclosure:

Dieterich has received consulting and speaking fees from Gilead, and consulting fees from VIR; Brunet has received a grant from Gilead Sciences for the current project through payments to Epividian, grants from AIDS Healthcare Foundation, EMD Serono, Gilead Sciences, Janssen Scientific Affairs, Merck & Co., Theratechnologies Inc., and ViiV Healthcare through payments to Epividian; Hsu received grants from Speaker honoraria from ViiV Healthcare, Merck, Gilead Sciences, and Janssen, and advisory board participation with ViiV Healthcare, Gilead Sciences, Janssen, and Epividian; Mounzer has received a grant from Gilead Sciences for the current project through payments to Epividian; Mounzer has received grants from Gilead Sciences and Epividian through payments to Philadelphia FIGHT; Pierone has received grants from GSK, ViiV Healthcase, and Abbvie through payments through the institution; Wohlfeiler has received grant from ViiV Healthcare and Epividian for being the Principal Investigator on ViiV Healthcare clinical trials, and has received personal fees for being on the Epividian Epidemiology and Clinical Advisory Board for Epividian; Fusco has received a grant from Gilead Sciences for the current project through payments to Epividian, and has received research funding from AIDS Healthcare Foundation, EMD Serono, Gilead Sciences, Janssen Scientific Affairs, Merck & Co., Theratechnologies Inc., and ViiV Healthcare; Dunbar is an employee and owns stock at Gilead Sciences; Yee is an employee and owns stock at Gilead Sciences; Frenette is an employee and owns stock at Gilead Sciences; Fusco has received research funding from AIDS Healthcare Foundation, EMD Serono, Gilead Sciences, Janssen Scientific Affairs, Merck & Co., Theratechnologies Inc., and ViiV Healthcare with payments made to Epividian. This research was sponsored by Gilead Sciences and the authors have declared no conflict of interest.

Acknowledgements:

The authors would like to thank Robin Beckerman (SAS programming), Michael Stagner (QA), Bernie Stooks (IT/data management), Lisa Lutzi and Nicole Shaw (data architecture), and Judy Johnson (medical terminology classification). This research would not be possible without the generosity of people living with HIV/HBV and their OPERA caregivers.

Citation:
EMJ Hepatol. ;12[1]:40-42. https://doi.org/10.33590/emjhepatol/SVUV5256.
Keywords:
Hepatitis B, hepatitis flare, HIV, monitoring, reactivation, tenofovir alafenamide, tenofovir disoproxil fumarate, treatment interruption.

Each article is made available under the terms of the Creative Commons Attribution-Non Commercial 4.0 License.

BACKGROUND AND AIMS

Among hepatitis B virus (HBV) core antibody positive (cAb+) people with HIV, suppressive HBV treatment, including either tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide (TAF), is recommended to prevent HBV reactivation and possibly fulminant or fatal hepatitis.1,2 The risk of HBV resistance is high if lamivudine is used without TDF or TAF, whereas the risk of HIV resistance is high if entecavir is used without TDF or TAF. The authors describe TDF/TAF interruptions and HBV monitoring practices in the USA, as well as assess the incidence of HBV reactivation and hepatitis flares during TDF/TAF interruptions in the OPERA cohort.

METHOD

The OPERA cohort includes electronic health records from >142,000 people with HIV receiving routine clinical care in the USA (96 clinics, 22 states, 1 USA territory), representing approximately 13% of people with diagnosed HIV infection in the USA at the time of this study.3 All TDF/TAF interruptions among HBV surface antigen positive (sAg+) and/or cAb+ people with HIV were categorised by risk of reactivation (high: sAg+; moderate: sAg-/cAb+/HBV surface antibody negative [sAb-]; low: sAg-/cAb+/sAb+).The presence of HBV DNA, sAg, and alanine transaminase (ALT) testing was assessed before (within ≤12 months) and during the interruption. The incidence of HBV reactivation and hepatitis flares (American Association for the Study of Liver Diseases definitions) was assessed with Poisson regression.

RESULTS

Of 30,549 people co-infected with HBV/HIV, 5,343 (17%) had ≥1 interruption, for a total of 6,252 interruptions (11% high, 19% moderate, 70% low-risk) and the median duration was 23 months (interquartile range: 4–53). There were no DNA tests before (high: 56%; moderate: 94%; low: 92%) or during interruptions (high: 48%; moderate: 91%; low: 95%). There was no sAg test in 75% of high, 69% of moderate, and 72% of low-risk interruptions. HBV reactivation occurred in 117 high-risk interruptions (17% overall, 32% of those with DNA tests) for an incidence rate [IR] of 9.92 per 100 person-years (95% CI: 8.28, 11.89). Reactivation occurred in 24 moderate-risk interruptions (2% overall, 6% of those with DNA and/or sAg tests), with an IR of 0.67 (95% CI: 0.45, 1.00). Only 10 low-risk interruptions resulted in HBV reactivation (<1% overall; <1% of those with DNA and/or sAg tests), with an IR of 0.08 (95% CI: 0.04, 0.15). ALT tests were available before (high: 91%; moderate: 91%; low: 93%) and during interruptions (high: 99%; moderate: >99%; low: >99%). Hepatitis flares occurred in 68 (10%) high-risk interruptions (IR per 100 person-years: 5.53; 95% CI: 4.36, 7.01), 59 (5%) moderate-risk interruptions (IR: 1.74; 95% CI: 1.35,2.24), and 162 (4%) low-risk interruptions (IR: 1.31; 95% CI: 1.13, 1.53).

CONCLUSION

In this large USA cohort of sAg+ and/or cAb+ people with HIV receiving care in primary or HIV care clinics, TDF/TAF interruptions were common and lengthy, and HBV lab monitoring was sub-optimal, suggesting that primary and HIV care providers tend to be unaware of HBV status or overlook HBV monitoring and management in people with co-infection. While sAg+ individuals had the highest HBV reactivation and hepatitis flare risk, all were at risk regardless of serology. Given infrequent testing, many reactivations were likely missed. Primary and HIV care providers need to incorporate HBV monitoring in their standard of care and proceed with caution if considering a TDF/TAF interruption for people with
HBV/HIV co-infection.

References
Terrault NA et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018;67(4):1560-99. Clinicalinfo. Panel on Antiretroviral Guidelines for Adults and Adolescents, Department of Health and Human Services. Guidelines for the use of antiretroviral agents in adults and adolescents with HIV 2024. Available at: https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-arv/whats-new. Last accessed: 14 June 2024 Centers for Disease Control and Prevention (CDC). HIV Surveillance Report, 2021. 2023. Available at: https://stacks.cdc.gov/view/cdc/149071. Last accessed: 31 May 2023.

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