Hepatitis B, a viral infection that primarily affects the liver, can lead to serious complications, such as cirrhosis and hepatocellular carcinoma. In individuals living with HIV, the situation is further complicated since they face the risk of Hepatitis B reactivation – a condition that can occur when switching to antiretroviral therapy (ART) lacking Hepatitis B activity. This comprehensive article explores this complex medical phenomenon, providing a detailed understanding of its causative factors, implications, and potential strategies for patient management.
In the landscape of HIV and Hepatitis B co-infection, it is observed that HIV-positive individuals exhibit a higher prevalence of Hepatitis B, as indicated by the presence of positive Hepatitis B core antibodies (cAb+). This prevalence is significantly higher in HIV-positive individuals, with one in three persons being cAb+, compared to just 3.5-4% in the overall US population. These patients can be further categorized into those with an isolated positive core antibody (cAb+), and those with both a positive core and surface antibody (sAb+).
In these patients, the reactivation of Hepatitis B can occur spontaneously due to the immune suppression brought about by HIV/AIDS. It can also be triggered by the cessation of dually active antiretroviral therapy (ART). This reactivation has been observed in both retrospective case reports and series, as well as a prospective study conducted in Cameroon, where it was found that a significant 10% of cAb+ participants experienced Hepatitis B reactivation when ART containing NRTI was withdrawn.
The concern for Hepatitis B reactivation becomes particularly pronounced when patients are switched to ART regimens that lack Hepatitis B-active components. These components include tenofovir, emtricitabine, and lamivudine. Such regimens are often perceived as more attractive by clinicians and patients due to certain factors. These include the presence of comorbidities like chronic kidney disease, and concerns about the long-term side effects of standard three-drug regimens. However, it’s important to note that there is a potential risk of Hepatitis B flare or worsening, as indicated in the FDA label for dolutegravir + rilpivirine and cabotegravir + rilpivirine combinations. The exact frequency of this risk, however, remains uncertain.
To better grasp the risk and prevalence of Hepatitis B reactivation upon switching to ART without Hepatitis B activity, a study was conducted encompassing HIV-positive patients who had made the switch prior to the end of 2022 and were at risk for Hepatitis B reactivation. These patients were identified as not having active Hepatitis B, as indicated by negative sAg and HBV DNA (if checked).
The primary outcome of the study was Hepatitis B reactivation (HBVr), defined as any new sAg positivity and/or newly detectable HBV DNA on the nearest result prior to the switch. The results revealed that out of the ‘at risk’ cohort, 89 total HBVr cases occurred after the date of the switch. Among those who continued with ART without Hepatitis B activity prior to reactivation, 39 HBVr cases were confirmed.
In terms of clinical implications, it was observed that approximately 32% of these individuals had an ALT (Alanine Aminotransferase) level greater than 100 at the time of HBVr. Additionally, around 41% were hospitalized at the time of HBVr, excluding mental health admissions. One case started hepatitis C treatment with direct-acting antivirals just four weeks prior to HBVr.
The study also presented case examples to illustrate the sequence of events leading to HBVr. In one case, a patient, after being on a regimen of Lopinavir + ritonavir + TAF + FTC, switched to dolutegravir plus rilpivirine in early 2019. Reactivation occurred a few months later in June 2019. The patient was then started on bictegravir + TAF + FTC a week later. In another case, a patient who was on Dolutegravir + TAF + FTC switched to bictegravir + TAF + FTC in May 2019, with reactivation occurring in July 2021.
An interesting finding from the study was the median time to reactivation, which was found to be 292 days. This suggests that HBVr is not an immediate consequence of switching to ART without Hepatitis B activity but can occur several months after the switch. This information is valuable for clinicians in managing patients’ follow-ups and for patients to understand the timeline of potential risks.
While the study provides valuable insights, there are several limitations that need to be considered. The study’s retrospective nature, the use of prescription fill data to determine ‘stop’ dates for ART, the lack of standardization in the timing of Hepatitis B screening/testing, and the complex and multifactorial nature of HBVr make it difficult to attribute causation and may affect the generalizability of the findings. As such, additional prospective research is beneficial to determine whether serial monitoring of serology or HBV DNA is feasible and beneficial for these patients.
Despite these limitations, the study offers critical insights into Hepatitis B reactivation after switching to ART without Hepatitis B activity in HIV-positive individuals. The data suggest that this occurrence is infrequent in individuals who are cAb+ but sAg- prior to the switch. This information can guide discussions between healthcare providers and patients who are cAb+ regarding their risk of HBVr if they switch to ART without Hepatitis B activity.
Interestingly, the study found that compared to those with isolated cAb+, individuals who are also sAb+ have a lower risk of HBVr. This suggests that the presence of surface antibodies could potentially offer some level of protection against reactivation. However, more research is needed to better understand the incidence and predictors of HBVr in the context of ART switch.
The study also acknowledges the contributions of various co-investigators, mentors, and the VACS Liver Working Group. These collaborative efforts underline the importance of multidisciplinary approaches in understanding complex health issues like HBVr in individuals with HIV.
In conclusion, the reactivation of Hepatitis B in HIV patients switching to ART without Hepatitis B activity is a complex issue that requires careful management and further research. It is essential for patients and healthcare providers to remain updated on the latest research in this area. By staying informed about the risk and management of HBVr, more effective treatment strategies can be developed, ultimately leading to improved patient outcomes and a better quality of life for individuals living with HIV and Hepatitis B. The commitment to ongoing research and collaboration among various stakeholders is key to achieving these goals.
