Surreal illustration representing the intersection of HIV, HBV, and drug resistance in a medical context.

HBV and HIV: Why Lamivudine Resistance is Skyrocketing in Co-infected Patients

Jordan Keane in Health & Wellness December 2025 • 4 min read.

"New research from China highlights the urgent need for vigilance in managing HBV drug resistance in HIV/HBV co-infected individuals undergoing antiretroviral therapy."

Chronic hepatitis B virus (HBV) infection remains a significant global health concern, affecting approximately 240 million people worldwide. Left unmanaged, HBV can lead to severe liver diseases, including cirrhosis and hepatocellular carcinoma, underscoring the importance of effective prevention, management, and treatment strategies, especially in regions with high HBV prevalence.

The available treatments for chronic hepatitis B, such as interferon and nucleos(t)ide analogues (NAs), aim to suppress HBV replication and prevent disease progression. However, these treatments are not curative and can lead to the emergence of drug-resistant mutations, posing a major challenge to long-term management. For instance, lamivudine (3TC) monotherapy can result in substitutions in the YMDD motif of the HBV reverse transcriptase in a majority of patients after several years of treatment.

The situation becomes further complicated by the dual activity of some NAs against both HBV and human immunodeficiency virus (HIV). This overlap can lead to higher rates of HBV genetic variability if HBV status is unknown before HIV treatment. With the rise of highly active antiretroviral therapy (HAART), liver-related diseases have emerged as a leading threat for HIV-infected individuals, making the management of HBV/HIV co-infection a critical area of focus.

Why is Drug Resistance a Growing Concern in HBV/HIV Co-infected Patients?

Surreal illustration representing the intersection of HIV, HBV, and drug resistance in a medical context.

A recent study published in Intervirology sheds light on the concerning prevalence of lamivudine-resistant mutations in HBV among HIV/HBV co-infected patients undergoing antiretroviral therapy (ART). The research, conducted in Guangxi, China—a region with the highest HIV/HBV co-infection rate in the country—revealed that a significant proportion of patients on ART developed resistance to lamivudine, a commonly used antiviral drug.

The study, which involved 203 co-infected subjects, compared the prevalence of HBV drug-resistant mutations between drug-naïve patients and those receiving ART. The results indicated that the prevalence of HBV drug-resistant mutations in the ART group was significantly higher than in the drug-naïve group. Specifically, 76.5% of patients on ART exhibited drug-resistant mutations, compared to only 1.4% in the drug-naïve group.

L180M + M204I + L80I: This was the most frequently observed pattern of lamivudine-resistant mutations.
Cross-Resistance: 95% of subjects with resistant mutations showed cross-resistance to telbivudine and entecavir, limiting treatment options.
TDF Ineffectiveness: Tenofovir disoproxil fumarate (TDF) failed to completely suppress HBV replication in some patients.
High Viral Loads: A notable percentage of patients on ART still had high HBV viral loads, indicating ongoing viral replication despite treatment.

These findings underscore the importance of routine HBV screening and monitoring in HIV-infected individuals, as well as the careful selection of antiretroviral regimens to minimize the risk of drug resistance. Strategies to combat drug resistance may include the use of alternative antiviral agents, such as tenofovir alafenamide (TAF), which has shown a higher barrier to resistance compared to lamivudine. Additionally, optimizing adherence to ART and implementing therapeutic drug monitoring may help improve treatment outcomes and prevent the emergence of drug resistance.

What is the Takeaway?

The high prevalence of lamivudine-resistant mutations in HBV among HIV/HBV co-infected patients on ART is a concerning trend that requires proactive management and vigilance. By implementing routine screening, careful treatment selection, and adherence-promoting strategies, healthcare providers can mitigate the risk of drug resistance and improve outcomes for this vulnerable population. Continued research and surveillance are essential to optimize treatment approaches and prevent the further spread of drug-resistant HBV strains.

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This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1159/000493797, Alternate LINK

Title: High Prevalence Of Hbv Lamivudine-Resistant Mutations In Hbv/Hiv Co-Infected Patients On Antiretroviral Therapy In The Area With The Highest Prevalence Of Hiv/Hbv Co-Infection In China

Subject: Infectious Diseases

Journal: Intervirology

Publisher: S. Karger AG

Authors: Hui-Hua Jia, Kai-Wen Li, Qin-Yan Chen, Xue-Yan Wang, Tim J. Harrison, Shu-Jia Liang, Qing-Li Yang, Chao Wang, Li-Ping Hu, Chuang-Chuang Ren, Zhong-Liao Fang

Published: 2018-01-01

Everything You Need To Know

What specific challenges do HIV/HBV co-infected patients face regarding drug resistance?

HIV/HBV co-infected patients encounter significant challenges due to drug resistance, particularly with lamivudine. The study highlights a concerning prevalence of lamivudine-resistant mutations in HBV among those undergoing antiretroviral therapy (ART). The research shows that 76.5% of patients on ART exhibited drug-resistant mutations, compared to only 1.4% in the drug-naïve group. Specific mutations like L180M + M204I + L80I are frequently observed. This resistance often extends to other antivirals like telbivudine and entecavir, limiting treatment options. Furthermore, even with tenofovir disoproxil fumarate (TDF), some patients still experience ongoing HBV replication, indicating that standard treatments may not always be effective in this patient population. This underscores the need for vigilant screening, careful selection of ART regimens, and adherence to treatment to mitigate drug resistance.

How does lamivudine contribute to the development of drug-resistant mutations in HBV?

Lamivudine, a nucleos(t)ide analogue (NA), is used to suppress HBV replication. However, it can lead to the emergence of drug-resistant mutations. The primary mechanism involves substitutions in the YMDD motif of the HBV reverse transcriptase, which occurs in a majority of patients after years of treatment. This is further complicated in HIV/HBV co-infected patients on antiretroviral therapy (ART), where the overlap in activity of some NAs against both viruses can lead to higher rates of HBV genetic variability if HBV status is unknown prior to HIV treatment. The study indicates that lamivudine-resistant mutations are significantly more prevalent in the ART group compared to drug-naïve patients. The use of lamivudine monotherapy in the context of HIV treatment can thus inadvertently foster the development of resistance, making HBV management more difficult.

What are the implications of cross-resistance in HBV treatment for co-infected patients?

Cross-resistance, as observed in the study, means that resistance to one antiviral drug often confers resistance to other similar drugs. For instance, 95% of the subjects with lamivudine-resistant mutations showed cross-resistance to telbivudine and entecavir. This severely limits the available treatment options, as it reduces the number of effective antiviral agents that can be used to control HBV. This is particularly problematic for HIV/HBV co-infected patients, where the treatment regimen must effectively manage both viruses. Limited options increase the complexity of treatment and potentially lead to poorer outcomes, as healthcare providers must navigate a narrower selection of effective drugs to suppress HBV replication and prevent liver disease progression.

Why is routine screening and monitoring essential for HIV-infected individuals, considering HBV?

Routine HBV screening and monitoring are crucial in HIV-infected individuals because of the high prevalence of HBV and the potential for severe liver diseases, such as cirrhosis and hepatocellular carcinoma. Co-infected patients, especially those undergoing ART, are at increased risk of developing drug-resistant HBV strains. The study emphasizes that the prevalence of HBV drug-resistant mutations is significantly higher in the ART group compared to the drug-naïve group. Early detection through screening allows for prompt initiation of appropriate treatment regimens. Regular monitoring helps assess treatment effectiveness and detect the emergence of drug resistance. These strategies enable healthcare providers to make timely adjustments to treatment plans, ensuring that HBV replication is effectively suppressed and preventing the progression of liver disease, thereby improving the overall health outcomes for this vulnerable population.

How can healthcare providers address the growing concern of lamivudine resistance in HIV/HBV co-infected patients?

Healthcare providers can address the rising concern of lamivudine resistance in HIV/HBV co-infected patients through multiple strategies. First, implementing routine screening for HBV in HIV-infected individuals is paramount, along with careful treatment selection, which includes considering alternative antiviral agents like tenofovir alafenamide (TAF). TAF has demonstrated a higher barrier to resistance compared to lamivudine. Optimizing adherence to ART is crucial because consistent adherence is key to suppressing viral replication and preventing the development of drug resistance. Therapeutic drug monitoring can also be employed to ensure that patients are receiving the correct dosages and that the drugs are effectively reaching the target cells. Furthermore, continued research and surveillance are essential to better understand the mechanisms of drug resistance and to develop more effective and durable treatment approaches, ultimately improving outcomes for this vulnerable population.