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When the last HYDRA head Gideon Malick orchestrated the return of the Inhuman Hive from Maveth back to Earth, he thought he would be generously rewarded once Hive conquers the world. Acting on his lifelong beliefs, Malick did everything he could to help Hive spread his power. However, Malick quickly lost influence within HYDRA and his own daughter Stephanie was killed by Hive. Malick eventually realized his mistake; he had freed the devil instead of the HYDRA god he had worshiped. When S.H.I.E.L.D. captured Malick, he told Director Phil Coulson everything he knew about HYDRA, to avenge Stephanie and help his former enemies stop Hive.
Coulson quickly passed Malick's intel to Brigadier General Glenn Talbot. Using the full power of the Advanced Threat Containment Unit and the United States Armed Forces, Talbot led a full-scale assault on all known HYDRA bases. At least 17 bases and hideouts were captured, along with all the equipment and operatives working at these bases.
Hive, his Inhuman followers, and a remaining few human mercenaries escaped the decimation of HYDRA, creating a new base in Wyoming, but the dark Inhuman was too focused on creating a better world for Inhumans and raising an Inhuman army to care about reforming HYDRA. Without a head that cared about rebuilding it, the majority of HYDRA was left in shambles.
In the offensive, the US forces dealt a crippling blow to HYDRA. The US President Matthew Ellis announced to the public that HYDRA was eradicated. However, some HYDRA operatives escaped justice. Three members of the HYDRA faction that worshiped Hive, led by Kirk Vogel, managed to evade the authorities, and assembled in Union City, an abandoned town which was bought by Hive with Gideon Malick's money. They all died in Hive's unsuccessful attempt to turn them into Inhumans as a reward for their loyalty. Another high ranking member of HYDRA, Colonel Vasily Karpov, the leader of the Winter Soldier Program, was captured, tortured, and killed by Helmut Zemo, a former Sokovian officer on a quest to avenge the deaths of his family by destroying the Avengers. Using Karpov's files, Zemo managed to gain access to the HYDRA Siberian Facility where he killed the five Winter Soldiers who were sleeping in suspended animation.
However, despite all those losses, some support for HYDRA's ideology remained, evidenced by the graffiti found in some American cities.