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Thus, successful viruses, like pandemic human immunodeficiency virus 1 (HIV-1), evolved strategies to counteract or even exploit autophagy for efficient replication. Here, we provide an overview of the intricate interplay between autophagy and HIV-1. We discuss the impact of autophagy on HIV-1 replication and report in detail how HIV-1 manipulates autophagy in infected cells and beyond. We also highlight tissue and cell-type specifics in the interplay between autophagy and HIV-1. In addition, we weigh exogenous modulation of autophagy as a putative double-edged sword against HIV-1 and discuss potential implications for future antiretroviral therapy and curative approaches. Taken together, we consider both antiviral and proviral roles of autophagy to illustrate the ambivalent role of autophagy in HIV-1 pathogenesis and therapy.<\/jats:p>","DOI":"10.3390\/v16040500","type":"journal-article","created":{"date-parts":[[2024,3,25]],"date-time":"2024-03-25T12:50:49Z","timestamp":1711371049000},"page":"500","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Friends and Foes: The Ambivalent Role of Autophagy in HIV-1 Infection"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6592-8817","authenticated-orcid":false,"given":"Susanne","family":"Klute","sequence":"first","affiliation":[{"name":"Institute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8682-1779","authenticated-orcid":false,"given":"Konstantin M. 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