Antiretroviral therapy (ART) has transformed outcomes for people living with HIV, especially those also managing chronic hepatitis B virus (HBV) coinfection. But not all ART regimens have the same long-term impact on liver health, particularly in this high-risk population.

A newly published, real-world study from Gilead Sciences explores this question head-on. Using Verified electronic health records (EHR) and claims data from the HealthVerity Marketplace, the research evaluated liver disease outcomes among people with HIV/HBV coinfection who initiated ART in the United States between 2016 and 2024.¹ The findings could have significant implications for treatment strategy, especially as pharma leaders weigh how regimen choices influence not only viral suppression but downstream clinical complications like cirrhosis or liver cancer.

Liver complications in HIV and hepatitis B coinfection: What pharma needs to know

People living with both HIV and HBV face more severe liver-related complications than those with either virus alone. HIV accelerates HBV-induced liver damage, increasing the risk of cirrhosis, liver decompensation, hepatocellular carcinoma (HCC), and even liver transplants.

ART plays a dual role here. In addition to suppressing HIV, certain regimens, like those containing tenofovir, can reduce HBV replication and improve liver-related outcomes. Two forms of tenofovir are commonly used in ART:

• Tenofovir disoproxil fumarate (TDF): A long-established therapy effective against both HIV and HBV, but associated with concerns about bone and kidney toxicity.
  
  
• Tenofovir alafenamide (TAF): A newer formulation offering similar antiviral efficacy with a better safety profile.
  
  
• Non-tenofovir-based ART regimens, on the other hand, may not provide the same protection against HBV-related liver disease and are generally reserved for people unable to tolerate tenofovir.

Despite widespread use, real-world comparative data on liver outcomes across these regimens have been limited, until now.

Gilead’s study design: Real-world data from HealthVerity Marketplace

Gilead’s retrospective observational cohort study drew on de-identified EMR and claims data from HealthVerity Marketplace, which represents one of the nation’s largest, privacy-protected healthcare datasets. The study included 3,095 adults with documented HIV and HBV who started ART between 2016 and early 2024 (Figure 1).

Patients were grouped by initial ART regimen:

• 76% received TAF-based ART
• 13% received TDF-based ART
• 11% received non-tenofovir-based ART

Figure 1: Patient inclusion and final cohort for eligible patients

Researchers tracked advanced liver disease events and monitored liver enzyme trends for up to five years post-ART initiation.

This longitudinal approach, enabled by the breadth, precision, and stability of the HealthVerity Marketplace offered a unique window into how ART selection influences liver health over time.

Which ART regimens reduce liver risk? Real-world evidence favors tenofovir

The results were striking.

• Both TAF- and TDF-based ART regimens significantly reduced the risk of severe liver events compared to non-tenofovir regimens.
  
  
  • TAF-based ART reduced overall risk by 45% and cirrhosis risk by 58%.
    
    
  • TDF-based ART reduced overall risk by 55% but did not show a statistically significant reduction in cirrhosis.
    
    
• TAF-based ART was associated with a 72% lower risk of developing hepatocellular carcinoma (HCC) compared to non-tenofovir regimens.
  
  
• Liver enzymes (ALT, AST) remained stable or improved over time in the tenofovir groups, but not in the non-tenofovir group.
  
  

Figure 2: Adjusted hazard ratios (HRs) for advanced liver disease outcomes by ART regimen in people with HIV/HBV coinfection. Tenofovir-based ART, especially TAF, was associated with a lower risk of cirrhosis, liver decompensation, and hepatocellular carcinoma (HCC) compared to non-tenofovir-based regimens. Error lines represent 95% confidence intervals.

In short, tenofovir-based ART, especially TAF, was associated with a lower likelihood of long-term liver damage in people with HIV/HBV coinfection according to HealthVerity data.

What pharmaceutical teams can learn

For pharmaceutical companies developing, marketing, or evaluating ART regimens, these findings are more than academic.

• Clinical differentiation: Real-world liver outcome data can help distinguish newer tenofovir-based therapies (like TAF) from legacy options, supporting value-based care discussions and market positioning.
  
  
• Labeling and safety strategy: Observational data on cirrhosis and HCC risk reduction may inform post-market safety studies or regulatory engagement.
  
  
• Targeted research: Access to high-quality, longitudinal datasets like those available through HealthVerity Marketplace can help R&D teams explore patient subgroups, refine real-world evidence strategies, and track long-term treatment impact beyond viral suppression.

Explore another use-case of HealthVerity data from Johnson & Johnson's initiative to track how patients are treated after failing initial first-line therapy in non-muscle invasive bladder cancer.

To explore datasets like those used in this study, or design your next real-world research initiative, visit the HealthVerity Marketplace. With Verified data coverage, transparency, and stability, it supports your study at every stage.

References

1. Chuo CY, Zachry W, de Boer M, Telep L, Tao L. Advanced liver disease events in people with hiv and hepatitis b virus coinfection initiating antiretroviral therapy in the united states. Infect Dis Ther. Published online July 15, 2025.