biostudies-literatureFuchs SPU.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)8906https://www.ebi.ac.uk/biostudies/studies/S-EPMC12504686biostudies-literatureUnknown16(1)Long-term delivery of broadly neutralizing antibodies (bnAbs) using adeno-associated virus (AAV) vector is a promising approach for both the prevention and treatment of HIV infection. However, host anti-drug antibody (ADA) responses severely limit the continuous delivery of these anti-HIV bnAbs and have been the most important obstacle for development of this approach for widespread human use. Transient treatment with the immunomodulatory agent rapamycin (sirolimus) allows for continuous long-term delivery of the anti-HIV bnAb 3BNC117 in immunocompetent mice in the absence of detectable ADAs. Use of the agent in monkeys results in 12 of 15 successful deliveries of the bnAbs 3BNC117, 10-1074, and PGT145 following drug cessation across all animals. The results of this 5-monkey trial lend strNature communicationsTransient rapamycin treatment avoids unwanted host immune responses toward AAV-delivered anti-HIV antibodies.PMC12504686U19AI149646Martinez-Navio JMDudley DMZhen AZabizhin RCook EGao GWeisgrau KLMondragon PGWang LFurlott JCoonen JTomer SFuchs SPAlexander EXie JTermini JMDesrosiers RCfalseTransient rapamycin treatment avoids unwanted host immune responses toward AAV-delivered anti-HIV antibodies.Long-term delivery of broadly neutralizing antibodies (bnAbs) using adeno-associated virus (AAV) vector is a promising approach for both the prevention and treatment of HIV infection. However, host anti-drug antibody (ADA) responses severely limit the continuous delivery of these anti-HIV bnAbs and have been the most important obstacle for development of this approach for widespread human use. Transient treatment with the immunomodulatory agent rapamycin (sirolimus) allows for continuous long-term delivery of the anti-HIV bnAb 3BNC117 in immunocompetent mice in the absence of detectable ADAs. Use of the agent in monkeys results in 12 of 15 successful deliveries of the bnAbs 3BNC117, 10-1074, and PGT145 following drug cessation across all animals. The results of this 5-monkey trial lend str2025-01-01T00:00:00Z2025 Oct2026-06-04T06:24:10.72Z2026-05-06T03:13:24.004ZS-EPMC125046864105732310.1038/s41467-025-63970-6