Naive T lymphocytes and recent thymic emigrants are associated with HIV-1 disease history in French adolescents and young adults infected in the perinatal period: the ANRS-EP38-IMMIP Study

Stéphane Blanche (1, 2) , Daniel Scott-Algara (3) , Jérôme Le Chenadec (4) , Céline Didier (3) , Thomas Montange (5) , Véronique Avettand-Fenoel (6, 2) , Christine Rouzioux (6, 2) , Adeline Mélard (6, 2) , Jean-Paul Viard (7, 2) , Catherine Dollfus (8) , Naima Bouallag (4) , Josiane Warszawski (9, 4) , Florence Buseyne (5)

1 Service d'immuno-hématologie pédiatrique [CHU Necker]
2 Infections à Vih, Réservoirs, Pharmacologie des Antirétroviraux et Prévention de la Transmission Mère Enfant
3 Régulation des Infections Rétrovirales
4 CESP - Centre de recherche en épidémiologie et santé des populations
5 EPVO (UMR_3569 / U-Pasteur_3) - Epidémiologie et Physiopathologie des Virus Oncogènes
6 Laboratoire de Virologie [CHU Necker]
7 Centre de Diagnostic et de Thérapeutique, Hôpital de l’Hôtel-Dieu [Paris]
8 CHU Trousseau [APHP]
9 UP11 - Université Paris-Sud - Paris 11

Background: Children born at the start of the HIV epidemic and infected during the perinatal period are now young adults living with the virus. Naive T-lymphocyte restoration is essential for the maintenance of a diverse TCR repertoire and for immunity to pathogens. Methods: The ANRS-EP38-IMMIP study included 93 patients infected with HIV-1 during the perinatal period. Naive CD4 (CD4N) and CD8 (CD8N) T lymphocytes and CD4 recent thymic emigrants (CD4RTE) were quantified in the peripheral blood by flow cytometry. Wilcoxon tests, Pearson’s correlation coefficients and linear regressions were used to study their associations with HIV disease parameters. Results: Median (IQR) CD4N, CD8N and CD4RTE percentages were 56% (44-64), 31% (22-44) and 79% (74-83), respectively. The three T-lymphocyte subsets were positively correlated with CD4 T-cell count. Patients aviremic at the time of the study tended to have a lower CD4N percentage (55% vs. 58%, P=0.10), had a significantly higher CD8N percentage (39% vs. 22%, P<0.0001), and a significantly lower CD4RTE percentage (77% vs. 81%, P=0.003) than viremic patients. In aviremic patients, CD4N percentages were positively associated with cumulative viremia over the last 10 years (r=0.335, P=0.01) and were significantly higher in patients harboring X4R5 viruses than in those harboring R5 viruses (61 vs. 44%, P=0.001). Conclusion: After at least 15 years of HIV infection, perinatally infected youths had preserved CD4N and CD4RTE levels. This persistence of high levels of thymic activity potentially compensating for the deleterious effects of current and past HIV replication is remarkable.

Mots clés: perinatal HIV infection; adolescents; naive T lymphocyte; thymus; CD4 T-cell count; cumulative viremia

Domaines: Immunité adaptative; Virologie; Maladies infectieuses; Pédiatrie

Stéphane Blanche, Daniel Scott-Algara, Jérôme Le Chenadec, Céline Didier, Thomas Montange, et al.. Naive T lymphocytes and recent thymic emigrants are associated with HIV-1 disease history in French adolescents and young adults infected in the perinatal period: the ANRS-EP38-IMMIP Study. Clinical Infectious Diseases, 2014, 58 (4), pp.573. ⟨10.1093/cid/cit729⟩. ⟨pasteur-01418085⟩