Editor's Note: Due to similar transmission routes, approximately 20% of people living with HIV (PLWH) are co-infected with hepatitis B virus (HBV). For decades, rhesus macaques (RMs) have served as a model for HIV research, but they have never been used to study HIV/HBV co-infection. At the AIDS 2024 conference, a research team from Oregon Health & Science University presented an oral report on their successful construction of an RM model co-infected with SHIVDH12 Clone 7 and HBV genotype D. A key advantage of this animal model is the ability to obtain longitudinal biopsies and dynamically monitor changes in immune cell phenotypes and ALT levels, providing better insights into the pathogenesis of co-infection. This article invites Dr. Linghua Li’s team from Guangzhou Eighth People's Hospital, Guangzhou Medical University to delve into this study and interpret the deeper significance behind these research findings.The research team used a chimeric virus, SHIVDH12 Clone 7, to infect rhesus macaques (RMs) with HIV/SIV and HBV. After co-infection, RMs were administered antiretroviral therapy (ART) drugs. Blood samples were collected weekly to monitor infection and immune response. Longitudinal liver biopsies were conducted to assess liver fibrosis. One RM exhibited chronic co-infection for over 76 weeks, making it the first animal model of chronic SHIV/HBV co-infection. ART suppressed viremia but had no effect on HBsAg levels. Dolutegravir monotherapy led to HBV viremia rebound. The study established a chronic co-infection model in RMs with ART outcomes similar to clinical HIV/HBV co-infected patients, simulating ALT flare-ups observed during ART.
Expert Commentary
The pathogenesis of HIV/HBV co-infection, especially the associated immune mechanisms, remains poorly understood due to the lack of appropriate animal models. This study successfully established a chronic SHIV/HBV co-infection model in rhesus macaques, with a key advantage being the ability to perform longitudinal biopsies and dynamic monitoring. This allows researchers to closely observe changes in immune cell phenotypes, fluctuations in ALT levels, and the progression of liver fibrosis during infection and ART treatment. The model provides direct evidence for understanding the hepatic immune pathogenesis of co-infection. Additionally, the suppression of viremia and the surge in ALT levels observed in co-infected RMs during ART treatment were similar to those seen in clinical HIV/HBV co-infected patients, suggesting that this model may partially replicate the therapeutic responses in human patients. However, it is important to consider the differences in viral species and immune responses between this model and human HIV/HBV infection. Future studies should further validate the model’s applicability across different genotypes and viral variants to ensure the reliability of its results.
