# An AAV-mediated functional cure and its impact on the reservoir > **NIH NIH U19** · SCRIPPS FLORIDA · 2021 · $2,834,491 ## Abstract PROGRAM SUMMARY In preliminary data we show the results of two studies demonstrating that a sustained state of ART-free virologic remission, a ‘functional cure’, is possible in non-human primates. First, the Desrosiers laboratory has shown that long-term expression of two broadly neutralizing antibodies (bNAbs) can suppress an untreated SHIV-AD8 infection in three rhesus macaques, in one case, to undetectable (<15 copies/ml) for over two years. Second, the Farzan laboratory has shown that long-term expression of the antibody-like entry inhibitor eCD4-Ig can also efficiently suppress viral replication in five of six SHIV-AD8-infected rhesus macaques for more than a year after cessation of anti-retroviral therapy (ART). We propose to build on these initial results by making these functional cures safer, more consistent, and more robust. In the process, we will establish a useful platform for evaluating latency-reversing agents (LRAs), a so-called ‘kick’, by providing an environment in which a potent ‘kill’ is always present, and develop a way to halt transgene expression, thereby enabling time-to-rebound measurements. We will determine how best to limit anti-drug antibodies (ADA) that emerge with AAV-expressed bNAbs. We will determine how to best use ART or the long-lasting integrase inhibitor cabotegravir to establish AAV-mediated functional cures. Finally, we will determine whether a sustained and potent kill can by itself change the decay rate of latently infected cells. To do so, we have assembled a team with deep experience in HIV and SIV studies, years of experience working together, and a long-term commitment to understanding and improving AAV-based functional cures. These effort are accomplished with four projects and three cores. Project 1 will establish robust functional cures in SHIV-AD8- and SIVmac239-infected macaques using AAV-expressed eCD4-Ig and evaluate the impact of sustained eCD4-Ig on the viral reservoir. Project 2 will develop and test multiple approaches for eliminating anti-drug antibodies that frequently emerge with AAV-expressed bNAbs. Project 3 will assess the impact of triple therapy and long-acting cabotegravir on the establishment of eCD4-Ig- mediated functional cures, and determine how cabotegravir might best be combined with eCD4-Ig. Project 4 will develop a permanent off- and on-switches for AAV transgenes, facilitating time-of-rebound studies after sustained bNAb expression and increasing the safety of AAV-mediated functional cures. These projects are organized around a uniform experimental pipeline of assays supporting a series of non-human primate studies, established and implemented by Core B. Core A will manage regulatory and logistical aspects of the Program, and Core C will provide produce high-quality AAV particles for these studies, and improve its capacity for doing so. Collectively these efforts will develop and improve a viable approach to functional cures in humans, and provide tools and insight useful ... ## Key facts - **NIH application ID:** 10145586 - **Project number:** 5U19AI149646-02 - **Recipient organization:** SCRIPPS FLORIDA - **Principal Investigator:** Michael R. Farzan - **Activity code:** U19 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2021 - **Award amount:** $2,834,491 - **Award type:** 5 - **Project period:** 2020-04-15 → 2022-04-01 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10145586 ## Citation > US National Institutes of Health, RePORTER application 10145586, An AAV-mediated functional cure and its impact on the reservoir (5U19AI149646-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10145586. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*