Sensitive and convenient detection of HIV gene fragment is essential for the screening of acquired immunodeficiency syndrome (AIDS), as well as for timely medical intervention and effective management of the disease. Here, we present a cascade amplification strategy for sensitive and convenient detection of HIV gene fragment utilizing a personal glucose meter. Two amplification reactions, polymerization nicking reaction and cross primer exchange reaction, were cascaded to generate copious long single-strand DNA (ssDNA). These ssDNA facilitated the recruitment of DNA-invertase conjugate that catalyzed the hydrolysis of sucrose, generating a signal that could be detected by a personal glucose meter. As a proof of concept, a mock fragment of HIV gene was employed as the target, which could be detected with picomolar sensitivity. Moreover, the proposed strategy stayed robust in 10% diluted human serum and Hela cell lysate, suggesting its potential utility for detecting HIV gene fragments in real-world diagnostic scenarios.