The risk of hepatitis B virus (HBV) reactivation is a significant concern for individuals with HIV, particularly when undergoing treatment for HIV or receiving immunosuppressive therapies. Recent research and clinical guidelines highlight the complexities of managing this risk, with lamivudine emerging as a frequently used prophylactic agent, though not without caveats. Understanding the nuances of HBV reactivation and the appropriate use of antiviral therapies is crucial for optimizing patient care and preventing severe liver complications.
HBV reactivation refers to the reappearance of detectable HBV DNA in individuals with prior HBV infection, which can lead to liver inflammation and potentially liver failure. Individuals with HIV and a history of HBV infection are particularly vulnerable, as their immune systems may be compromised by both viruses. The risk is heightened when HIV-positive individuals start or stop HIV treatment, or when they receive immunosuppressive drugs for other conditions. Effective management requires careful monitoring and, in many cases, preemptive antiviral therapy.
Lamivudine, an oral antiviral medication, has been a mainstay in the prevention of HBV reactivation. According to research published in 2019, randomized clinical trials have assessed the benefits and harms of lamivudine in preventing clinical HBV-related hepatitis or virological HBV-reactivation in individuals positive for the hepatitis B surface antigen (HBsAg) who are about to receive immunosuppressive therapy [1]. However, recent studies suggest that lamivudine may not always be the most effective prophylactic option. A study highlighted in the European Journal of Hospital Pharmacy found that the use of lamivudine as prophylactic treatment in patients with a history of HBV infection undergoing treatment with high-risk immunosuppressants was associated with a higher likelihood of reactivation compared to other antivirals [4].
The development of resistance to lamivudine is a well-documented challenge in chronic HBV infection. Mutations in the HBV polymerase gene, specifically within the FLLA and YMDD motifs, contribute to this resistance [3]. These mutations, such as rtL180M and rtM204V/I, can render lamivudine ineffective, necessitating alternative treatment strategies. This underscores the importance of ongoing monitoring for viral resistance during long-term lamivudine therapy.
Understanding HBV Persistence
HBV’s ability to establish a persistent infection is linked to its unique characteristics. The virus exists as a circular DNA molecule, known as covalently closed circular DNA (cccDNA), which resides within the nucleus of infected liver cells. This cccDNA is remarkably stable and can persist for a lifetime, even in individuals receiving antiviral treatment [5]. The long half-life of hepatocytes further contributes to the persistence of HBV infection, making complete viral eradication a significant challenge.
Clinical Considerations and Prophylaxis Strategies
Current guidelines emphasize the importance of screening all HIV-positive individuals for HBV seromarkers (HBsAg, anti-HBs, and anti-HBc). For HBsAg-positive patients, antiviral therapy is generally recommended to suppress HBV replication and reduce the risk of liver disease progression. For HBsAg-negative, anti-HBc-positive individuals – those with resolved HBV infection – prophylactic antiviral therapy may be considered when initiating immunosuppressive treatment. A recent study demonstrated that 24-month-long prophylaxis with lamivudine is a safe and efficient choice for preventing HBV reactivation in this patient population undergoing chemotherapy for advanced diffuse large B-cell lymphoma [5].
However, as noted earlier, the choice of prophylactic agent should be individualized based on the patient’s risk factors, the type of immunosuppression being used, and the local prevalence of lamivudine resistance. Alternative antivirals, such as tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide (TAF), may be considered, particularly in patients at high risk of lamivudine resistance.
Future Directions
Research continues to focus on developing more effective strategies to prevent and treat HBV reactivation in HIV-positive individuals. This includes exploring novel antiviral agents, immunomodulatory therapies, and strategies to target and eliminate cccDNA from infected cells. Further studies are needed to refine risk stratification models and optimize prophylactic regimens to minimize the risk of HBV reactivation and improve long-term outcomes for these vulnerable patients.
The management of HBV reactivation in HIV-positive individuals remains a complex and evolving field. Continued vigilance, careful monitoring, and adherence to evidence-based guidelines are essential for providing optimal care.
Disclaimer: This information is intended for general knowledge and informational purposes only, and does not constitute medical advice. It is essential to consult with a qualified healthcare professional for any health concerns or before making any decisions related to your health or treatment.
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