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As well as different combinations of NNRTIs have been used on clinically approved combining highly active antiretroviral therapy (HAART) to resist the growth of HIV\u20101 and decrease the mortality rate of HIV\/AIDS. Although the feeble strength against the drug\u2010resistant mutant strains and the long\u2010term damaging effects have been reducing the effectiveness of HAART, it could be a crucial challenge to develop novel Anti\u2010HIV leads with a vital mode of action and the least side effects. The extensive chemical reactivity and the diverse chemotherapeutic applications of the 1,3,5\u2010triazine have provided a wide scope of research in medicinal chemistry via a structural modification. In this review, we focused on the Anti\u2010HIV profile of the tri\u2010substituted <jats:italic>s<\/jats:italic>\u2010triazine derivatives with structure\u2010based features and also discussed the active mode of action to evaluate the significant findings. The tri\u2010substituted 1,3,5\u2010triazine derivatives have been found more promising to inhibit the growth of the drug\u2010sensitive and drug\u2010resistant variants of HIV\u20101, especially HIV\u20101 wild\u2010type, HIV\u20101 K103N\/Y181C, and HIV\u20101 Tyr181Cys. It has been observed that these derivatives have interacted with the enzyme protein residues via a significant \u2010 interaction and hydrogen bonding to resist the proliferation of the viral genomes. Further, the SAR and the active binding modes are critically described and highlight the role of structural variations with functional groups along with the binding affinity of targeted enzymes, which may be beneficial for rational drug discovery to develop highly dynamic Anti\u2010HIV agents.<\/jats:p>","DOI":"10.1002\/ddr.22154","type":"journal-article","created":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T03:39:07Z","timestamp":1706758747000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Tri\u2010substituted 1,3,5\u2010triazine\u2010based analogs as effective HIV\u20101 non\u2010nucleoside reverse transcriptase inhibitors (NNRTIs): A systematic review"],"prefix":"10.1002","volume":"85","author":[{"given":"Zebabanu","family":"Khalifa","sequence":"first","affiliation":[{"name":"Department of Chemistry, Government College Daman (Affiliated to Veer Narmad South Gujarat University, Surat) Daman 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