Background: Despite antiretroviral drugs-mediated control of active HIV infection, cardiovascular disease (CVD) remains one of the leading causes of comorbidity in people living with HIV/AIDS (PLWHA). Recent studies suggest that activation of the immune system and chronic inflammation increases CVD risk in PLWHA. Dysregulation of the immune system can interact with several cellular functions, including autophagy and mitophagy. The autophagic factor Beclin1 is a crucial regulator of cellular autophagy and mitophagy. In this study, we tested the role of Beclin1 in cardiac function using a mice model of HIV. Methods and Results: This study was performed using transgenic mice of HIV-1 Tg26 mice, which was constructed before using HIV-1 DNA with deletion of 3-kb region of the gag/pol genes. Tg26 mice were crossed with Beclin1 transgenic mice to test the role of Beclin1. Cardiac function of Tg26 and Tg26 mice crossed with Beclin1 was evaluated by echocardiography. Cardiac autophagy was determined by western blots using autophagy regulatory markers. Our data suggest that Tg26 mice have significantly reduced cardiac function. Further, Tg26 mice show increased reactive Oxygen species (ROS) level, accumulation of LC3II, increased P62 level, and reduced autophagy flux. Additionally, western blots with cardiac tissue show upregulation of electron transport chain (ETC) complex proteins of mitochondria in the Tg26 mice that may be due to defective mitochondria accumulation in Tg26 mice heart. Interestingly, Beclin1 expression can improve the cardiac function of Tg26 mice heart. Mechanistically, we found that Beclin1 overexpression can restore the autophagy flux and reduce the cellular ROS level in the heart of Tg26 mice. Conclusion: Our study suggests that Beclin1 plays critical role in regulation of cardiac function during HIV induced cardiomyopathy and can be used as a potential therapeutic tool to control comorbidity in the PLWHA.