Tenofovir use is associated with a decreased risk of hepatocellular carcinoma among men with HIV irrespective of coinfection status

Mei-Hsuan Lee; Ping-Feng Wu; Tzu-I Chen; Chi Chan; Hsi-Hsun Lin; Yi-Hsiang Huang; Hsuan-Yu Chen; Yi-Tsung Lin; Chien-Jen Chen

doi:10.1016/j.jhepr.2022.100634

Tenofovir use is associated with a decreased risk of hepatocellular carcinoma among men with HIV irrespective of coinfection status

JHEP Rep. 2022 Nov 25;5(3):100634. doi: 10.1016/j.jhepr.2022.100634. eCollection 2023 Mar.

Authors

Mei-Hsuan Lee¹, Ping-Feng Wu^{1

2

3}, Tzu-I Chen⁴, Chi Chan¹, Hsi-Hsun Lin^{1

5

6}, Yi-Hsiang Huang^{1

7}, Hsuan-Yu Chen⁸, Yi-Tsung Lin^{3

9}, Chien-Jen Chen¹⁰

Affiliations

¹ Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
² Faculty of Medicine, Department of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
³ Division of Infectious Diseases, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
⁴ Graduate Institute of Business Administration, College of Management, Fu Jen Catholic University, New Taipei City, Taiwan.
⁵ Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
⁶ School of Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan.
⁷ Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
⁸ Institute of Statistical Science, Academia Sinica, Taipei, Taiwan.
⁹ Institute of Emergency and Critical Care Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
¹⁰ Genomics Research Center, Academia Sinica, Taipei, Taiwan.

Abstract

Background & aims: Tenofovir is recommended as part of the first-line antiretroviral therapy (ART) to treat people living with HIV (PLWH) with HBV coinfection. However, the effects of tenofovir-containing ART on hepatocellular carcinoma (HCC) risk among PLWH with/without chronic hepatitis virus infections remain unclear.

Methods: This study included 23,838 PLWH. All of them were males aged ≥20 years and followed prospectively during 2000-2017. Four major nationwide registries - the Human Immunodeficiency Virus surveillance database, Taiwan Cancer Registry, Death Certification System, and National Health Insurance Database - were applied to define ART and comorbidities and ascertain newly diagnosed HCC. Tenofovir-containing ART was identified through prescription records. Cox proportional hazards models were used to determine the association of tenofovir use with HCC incidence.

Results: HCC incidence was lower among ever users of tenofovir than among never users (24.2 and 85.7 per 100,000 person-years, respectively). Ever users had significantly reduced HCC risk (adjusted hazard ratio 0.20, 95% CI 0.13-0.31). The effect of tenofovir use on reduced risk for HCC consistently favored never users across many prespecified subgroups, including HBV or HCV coinfection (p <0.05). The findings were consistent in subgroups of PLWH diagnosed with HIV before tenofovir's approval and in those born before the nationwide roll-out of neonatal HBV vaccination.

Conclusions: Our findings underscore the need for randomized controlled trials of tenofovir in combination with long-acting injectable ART regimens to assess its safety and efficacy in PLWH, particularly in those with HBV or HCV coinfection.

Impact and implications: Tenofovir's effect on the risk of hepatocellular carcinoma (HCC) among people living with HIV with hepatitis B or C coinfection remains under investigated. This nationwide prospective cohort study, comprising 23,838 men living with HIV, showed that tenofovir-containing antiretroviral therapy was associated with reduced risk of HCC (adjusted relative risk: 0.20, 95% CI 0.13-0.31), which was consistently observed across many prespecified subgroups. The effect of tenofovir use on HCC risk should be further investigated in PLWH, particularly following the development of long-acting injectable ART regimens.

Keywords: AIDS; AIDS, acquired immunodeficiency syndrome; ART, antiretroviral therapy; HCC, hepatocellular carcinoma; HRs, hazard ratios; NHI, National Health Insurance; PLWH, people living with HIV; chronic hepatitis; nationwide registry; prospective study; risk assessment.