The HIV-1 reservoir landscape in persistent elite controllers and transient elite controllers Gasca-Capote, Carmen Lian, Xiaodong Gao, Ce Rosetto, Isabelle Jiménez León, Maria Reyes Gladkov, Gregory Camacho-Sojo, Maía Inés Pérez-Gomez, Alberto Gallego, Isabel López Cortes, Luis E. Bachiller, Sara Vitalle, Joana Rafii-El-Idrissi Benhnia, Mohamed Ostos, F.J. Collado-Romacho, Antonio R. Santos, Jesús Palacios, Rosario Gómez Ayerbe, Cristina Muñoz Medina, Leopoldo Ruiz-Sancho, Andres Frias, Mario Rivero-Juarez, Antonio Roca-Oporto, Cristina Hidalgo Tenorio, Carmen Rull, Ana Olalla, Julian López Ruz, Miguel Ángel Vidal, Francesc Viladés, Consuelo Mastrangelo, Andrea Cavassini, Matthias Espinosa, Nuria Matthias, Matthieu Peraire, Joaquin Rivero, Antonio López-Cortes, L. F. Lichterfeld, Mathias Yu, Xu G Ruiz-Mateos, Ezequiel FUNDING. Instituto de Salud Carlos III (FI17/00186, FI19/00083, MV20/00057, PI18/01532, PI19/01127 and PI22/01796), Gilead Fellowships (GLD22/00147). NIH grants AI155171, AI116228, AI078799, HL134539, DA047034, MH134823, amfAR ARCHE and the Bill and Melinda Gates Foundation. BACKGROUND. Persistent controllers (PCs) maintain antiretroviral-free HIV-1 control indefinitely over time, while transient controllers (TCs) eventually lose virological control. It is essential to characterize the quality of the HIV reservoir in terms of these phenotypes in order to identify the factors that lead to HIV progression and to open new avenues toward an HIV cure. METHODS. The characterization of HIV-1 reservoir from peripheral blood mononuclear cells was performed using next-generation sequencing techniques, such as full-length individual and matched integration site proviral sequencing (FLIP-Seq; MIP-Seq). RESULTS. PCs and TCs, before losing virological control, presented significantly lower total, intact, and defective proviruses compared with those of participants on antiretroviral therapy (ART). No differences were found in total and defective proviruses between PCs and TCs. However, intact provirus levels were lower in PCs compared with TCs; indeed the intact/defective HIV-DNA ratio was significantly higher in TCs. Clonally expanded intact proviruses were found only in PCs and located in centromeric satellite DNA or zinc-finger genes, both associated with heterochromatin features. In contrast, sampled intact proviruses were located in permissive genic euchromatic positions in TCs. CONCLUSIONS. These results suggest the need for, and can give guidance to, the design of future research to identify a distinct proviral landscape that may be associated with the persistent control of HIV-1 without ART. 2024-04-18T07:43:11Z 2024-04-18T07:43:11Z 2024-02-20 journal article Carmen Gasca-Capote et al. The HIV-1 reservoir landscape in persistent elite controllers and transient elite controllers. J Clin Invest. 2024;134(8):e174215. https://doi.org/10.1172/JCI174215 https://hdl.handle.net/10481/90865 10.1172/JCI174215 eng http://creativecommons.org/licenses/by-nc-nd/3.0/ open access Creative Commons Attribution-NonCommercial-NoDerivs 3.0 License American Society for Clinical Investigation