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Broadly neutralizing antibodies (bNAbs) have emerged as a promising approach for achieving durable HIV-1 remission. In this systematic review, we summarize recent advances in the development of bNAbs for HIV-1 treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We searched PubMed, Embase, and Web of Science for clinical trials published up to March\u202f22, 2026. We included data evaluating intravenously administered bNAbs, with or without concomitant conventional ART, and comparing them with placebo, ART or no intervention. These data were used to\u00a0evaluate the pharmacokinetics, antiviral efficacy, resistance profiles, immunologic effects, and safety of intravenously administered bNAbs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>LS-modified bNAbs extended half-life by 2- to 5-fold relative to their parental counterparts (e.g., VRC01LS: 71 vs 15\u00a0days), although viremia reduced half-life by 20\u201340%. In viremic participants harboring bNAb-sensitive virus, monotherapy achieved viral load (VL) reductions of 0.93\u20131.8 log\u2081\u2080\u00a0copies\/ml, with rebound occurring within approximately 4\u20138\u00a0weeks, whereas combinations regimens achieved declines of up to 2.04 log\u2081\u2080 copies\/ml and delayed rebound to 15\u201333\u00a0weeks. No consistent reduction in total reservoir size was observed, although early intervention and baseline viral sensitivity appeared to limit reservoir expansion. Resistance emerged through epitope-proximal mutations, with cross-resistance observed mainly among antibodies targeting shared epitope classes. Overall, bNAbs were well tolerated, with rare discontinuations (0.4%) and low immunogenicity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>LS-engineered bNAbs exhibit a longer half-life than their parental antibodies. Combination regimens achieve greater VL reductions and a longer delayed rebound compared with monotherapy, indicating that LS-modified multi-epitope bNAb cocktails are promising for long-acting HIV-1 remission. To become clinically competitive, larger resistance-guided trials are needed to extend dosing intervals, improve resistance mitigation, and define optimal integration with other long-acting therapies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s40249-026-01471-4","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T23:02:29Z","timestamp":1782946949000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Broadly neutralizing antibodies for HIV therapy in clinical trials: a systematic review"],"prefix":"10.1186","volume":"15","author":[{"given":"Jinfang","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayi","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinsong","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaye","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,2]]},"reference":[{"issue":"6","key":"1471_CR1","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1038\/s41579-024-01010-8","volume":"22","author":"M Armani-Tourret","year":"2024","unstructured":"Armani-Tourret M, Bone B, Tan TS, Sun W, Bellefroid M, Struyve T, et al. 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Time to HIV viral rebound and frequency of post-treatment control after analytical interruption of antiretroviral therapy: an individual data-based meta-analysis of 24 prospective studies. Nat Commun. 2025;16(1):906. https:\/\/doi.org\/10.1038\/s41467-025-56116-1.","journal-title":"Nat Commun"},{"key":"1471_CR5","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2024.102859","volume":"77","author":"L Ge","year":"2024","unstructured":"Ge L, Luo Y, Li X, Hu Y, Sun L, Bu F, et al. Global, regional, and national prevalence of HIV-1 drug resistance in treatment-naive and treatment-experienced children and adolescents: a systematic review and meta-analysis. 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