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Young Adults with Perinatally-Acquired HIV from Argentina Present Increased Naïve T-Cell Profile and Lower Intact Proviral HIV-DNA: Distinctive Strategies Needed for HIV Cure?

15 Pages Posted: 5 Mar 2024

See all articles by Lucia Baquero

Lucia Baquero

University of Buenos Aires (UBA)

Sofía Stöver

Hospital General de Agudos Dr. Juan A. Fernández

Marie Armani-Tourret

Harvard University

Ailén Perbelis

University of Buenos Aires (UBA)

Alejandra Urioste

University of Buenos Aires (UBA)

Ariel Amadeo Osegueda Peña

University of Buenos Aires (UBA)

Leonel Hernán Cruces

University of Buenos Aires (UBA)

Patricia Coll

Hospital General de Agudos Dr. Juan A. Fernández

Jorge Lattner

Hospital General de Agudos Dr. Juan A. Fernández

Alicia Sisto

Hospital General de Agudos Dr. Juan A. Fernández

María José Rolón

Hospital General de Agudos Dr. Juan A. Fernández

Solange Arazi

Hospital Nacional de Pediatría Pr. Dr. Juan P. Garrahan

Yanina Ghiglione

University of Buenos Aires (UBA)

María Laura Polo

University of Buenos Aires (UBA)

Xu Yu

Ragon Institute of MGH, MIT and Harvard

Matthias Lichterfeld

Ragon Institute of MGH, MIT and Harvard

Gabriela Turk

University of Buenos Aires (UBA)

Natalia Laufer

University of Buenos Aires (UBA)

More...

Abstract

Background: Perinatal transmission of HIV still constitutes a global health problem. Data on young adults who acquired HIV perinatally (p-YA) is scarce. We aimed to characterize the immune functionality and phenotype and the viral reservoir composition in a cohort of p-YA from Argentina.

Methods: Immune memory/effector phenotype, exhaustion, activation, PTK-7 and Ki-67 expression were evaluated by flow cytometry on NK and T-cells from 18 p-YA, 14 young adults with non-perinatally acquired HIV matched by age with p-YA and 15 adults with non-perinatally acquired HIV, matched by time from HIV diagnosis with p-YA, enrolled in Argentina. Total, intact and defective proviral (TP, IP and DP) HIV-DNA were measured in CD4 T-cells (CD4TC) by IPDA. Soluble markers were determined by ELISA.

Findings: p-YA presented higher expression of PD-1, lower levels of CD38+ CD4TC and further up levels of naïve T-cells than control groups. Also, lower levels of IP HIV-DNA according to absolute CD4TC counts and IP HIV-DNA/%naïve CD4TC were found in p-YA.

Interpretation: The higher naïve CD4TC frequency in p-YA cannot be explained by elevated thymic-activity nor a higher proliferation rate in the present. This disbalance could have been generated early in life and persisted during adulthood. Naïve CD4TC may not serve as a main viral reservoir in p-YA. Also, the lower PD-1+ CD4TC counts suggests that p-YA did not present higher levels of exhaustion. These findings suggest that acquiring HIV perinatally may imply different challenges for reaching a cure.

Funding: This work was supported by Bunge & Born Foundation (Grant 2018).

Declaration of Interest: All authors declare no conflicts of interest.

Ethical Approval: The study has been reviewed and approved by the “Comité de Ética en Investigación” from the hospital “Dr. JA Fernandez” (11/22/2018, Buenos Aires, Argentina). All participants signed an informed consent prior to sample collection. Participants data was encoded and deidentified to protect their confidentiality.

Keywords: HIV, perinatal transmission, immune phenotype, reservoir, naïve cells

Suggested Citation

Baquero, Lucia and Stöver, Sofía and Armani-Tourret, Marie and Perbelis, Ailén and Urioste, Alejandra and Osegueda Peña, Ariel Amadeo and Cruces, Leonel Hernán and Coll, Patricia and Lattner, Jorge and Sisto, Alicia and Rolón, María José and Arazi, Solange and Ghiglione, Yanina and Polo, María Laura and Yu, Xu and Lichterfeld, Matthias and Turk, Gabriela and Laufer, Natalia, Young Adults with Perinatally-Acquired HIV from Argentina Present Increased Naïve T-Cell Profile and Lower Intact Proviral HIV-DNA: Distinctive Strategies Needed for HIV Cure?. Available at SSRN: https://ssrn.com/abstract=4743677 or http://dx.doi.org/10.2139/ssrn.4743677

Lucia Baquero

University of Buenos Aires (UBA) ( email )

Sofía Stöver

Hospital General de Agudos Dr. Juan A. Fernández ( email )

Marie Armani-Tourret

Harvard University ( email )

Ailén Perbelis

University of Buenos Aires (UBA) ( email )

Alejandra Urioste

University of Buenos Aires (UBA) ( email )

Ariel Amadeo Osegueda Peña

University of Buenos Aires (UBA) ( email )

Leonel Hernán Cruces

University of Buenos Aires (UBA) ( email )

Patricia Coll

Hospital General de Agudos Dr. Juan A. Fernández ( email )

Jorge Lattner

Hospital General de Agudos Dr. Juan A. Fernández ( email )

Alicia Sisto

Hospital General de Agudos Dr. Juan A. Fernández ( email )

María José Rolón

Hospital General de Agudos Dr. Juan A. Fernández ( email )

Solange Arazi

Hospital Nacional de Pediatría Pr. Dr. Juan P. Garrahan ( email )

Yanina Ghiglione

University of Buenos Aires (UBA) ( email )

María Laura Polo

University of Buenos Aires (UBA) ( email )

Xu Yu

Ragon Institute of MGH, MIT and Harvard ( email )

Boston, MA
United States

Matthias Lichterfeld

Ragon Institute of MGH, MIT and Harvard ( email )

Boston, MA
United States

Gabriela Turk

University of Buenos Aires (UBA) ( email )

Natalia Laufer (Contact Author)

University of Buenos Aires (UBA) ( email )