@misc{10481/90865, year = {2024}, month = {2}, url = {https://hdl.handle.net/10481/90865}, abstract = {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.}, organization = {Instituto de Salud Carlos III (FI17/00186, FI19/00083, MV20/00057, PI18/01532, PI19/01127, PI22/01796)}, organization = {Gilead Fellowships (GLD22/00147)}, organization = {NIH grants AI155171, AI116228, AI078799, HL134539, DA047034, MH134823, amfAR ARCHE}, organization = {Bill and Melinda Gates Foundation}, publisher = {American Society for Clinical Investigation}, title = {The HIV-1 reservoir landscape in persistent elite controllers and transient elite controllers}, doi = {10.1172/JCI174215}, author = {Gasca-Capote, Carmen and Lian, Xiaodong and Gao, Ce and Rosetto, Isabelle and Jiménez León, Maria Reyes and Gladkov, Gregory and Camacho-Sojo, Maía Inés and Pérez-Gomez, Alberto and Gallego, Isabel and López Cortes, Luis E. and Bachiller, Sara and Vitalle, Joana and Rafii-El-Idrissi Benhnia, Mohamed and Ostos, F.J. and Collado-Romacho, Antonio R. and Santos, Jesús and Palacios, Rosario and Gómez Ayerbe, Cristina and Muñoz Medina, Leopoldo and Ruiz-Sancho, Andres and Frias, Mario and Rivero-Juarez, Antonio and Roca-Oporto, Cristina and Hidalgo Tenorio, Carmen and Rull, Ana and Olalla, Julian and López Ruz, Miguel Ángel and Vidal, Francesc and Viladés, Consuelo and Mastrangelo, Andrea and Cavassini, Matthias and Espinosa, Nuria and Matthias, Matthieu and Peraire, Joaquin and Rivero, Antonio and López-Cortes, L. F. and Lichterfeld, Mathias and Yu, Xu G and Ruiz-Mateos, Ezequiel}, }