Distinct viral reservoirs and immune signatures in individuals on long-term antiretroviral therapy with perinatally acquired HIV-1
Early initiation of antiretroviral therapy (ART) following HIV-1 infection restricts the size of the latent reservoir, following both horizontal and vertical infections. Here, we comprehensively profile the reservoirs and immunological milieus of nine young adults who acquired HIV-1 perinatally and remained on suppressive long-term ART (median: 20 years) since infancy (LeukoHIV cohort). Genome-intact reservoirs are markedly smaller compared to a cohort of adults on suppressive ART started in adulthood, with some LeukoHIV individuals characterized by an absence or near absence of intact proviruses in up to a billion peripheral blood mononuclear cells (PBMCs). Higher frequencies of functional CD56<sup>bright</sup> natural killer (NK) cells with increased cytotoxic activity are detectable in the LeukoHIV cohort compared to an adult reference cohort, while one LeukoHIV participant displayed a potent HIV-1-specific CD8<sup>+</sup> T cell response. Collectively, our data suggest that long-term ART initiated in early life following perinatal transmission may facilitate an immune environment better equipped to restrict the HIV-1 reservoir.
Authors
- Arianna Rotili (ORCID: https://orcid.org/0009-0003-2272-5184)
- Catherine K. Koofhethile (ORCID: https://orcid.org/0000-0001-5475-413X)
- Bruce D. Walker (ORCID: https://orcid.org/0000-0001-6122-9245)
- David R. Collins (ORCID: https://orcid.org/0000-0001-7903-346X)
- Alessia Neri (ORCID: https://orcid.org/0000-0002-6441-2800)
- Mathias Lichterfeld (ORCID: https://orcid.org/0000-0001-9865-8350)
- Benjamin Bone (ORCID: https://orcid.org/0000-0002-5702-1756)
- Ce Gao (ORCID: https://orcid.org/0000-0002-3775-790X)
- Elena Morrocchi (ORCID: https://orcid.org/0000-0002-3243-9291)
- Paolo Palma (ORCID: https://orcid.org/0000-0002-3066-4719)
- G. Olivieri (ORCID: https://orcid.org/0000-0002-8465-3265)
- Giuseppe Rubens Pascucci (ORCID: https://orcid.org/0000-0002-5978-1193)
- Paolo Giorgi Rossi (ORCID: https://orcid.org/0000-0001-9703-2460)
- Chiara Pighi (ORCID: https://orcid.org/0000-0001-6163-0135)
- Weiwei Sun (ORCID: https://orcid.org/0000-0003-3399-7858)
- Libera Sessa (ORCID: https://orcid.org/0000-0002-9459-4932)
- Nicole Colantoni
- Mélanie Lancien (ORCID: https://orcid.org/0000-0003-3777-0271)
- Toong Seng Tan (ORCID: https://orcid.org/0000-0002-6751-5987)
- Isabelle Roseto (ORCID: https://orcid.org/0009-0008-2976-0720)
- Ann Chahroudi (ORCID: https://orcid.org/0000-0001-7479-9546)
- Xu G. Yu (ORCID: https://orcid.org/0000-0002-8295-884X)
- Karen Shapiro (ORCID: https://orcid.org/0000-0003-2678-3851)
- Stefania Bernardi (ORCID: https://orcid.org/0000-0001-5672-0881)
- Enrico Angelo Emili
- Nicola Cotugno (ORCID: https://orcid.org/0000-0002-7748-1581)
- Giovanna Del Principe
- Giovanna Leone
- Mpho J. Olatotse
- Leah Carrere (ORCID: https://orcid.org/0009-0000-2481-5501)
- Seohyun Hong (ORCID: https://orcid.org/0009-0005-8111-7773)
Institutions
- University of Rome Tor Vergata (IT)
- Brigham and Women's Hospital (US)
- Emory University (US)
- Ragon Institute of MGH, MIT and Harvard (US)
- Bambino Gesù Children's Hospital (IT)
Publication Details
- Journal
- Cell Reports Medicine
- Published
- 2025-05-29
- DOI
- https://doi.org/10.1016/j.xcrm.2025.102150
- Citations
- 13
- Primary Topic
- HIV Research and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 13.47