Increased frequency of naïve T cell is a distinctive characteristic of young adults with perinatal HIV infection

SOFIA STOVER; ALEJANDRA URIOSTE; JORGE LATTNER; PATRICIA COLL; ALICIA SISTO; MARÍA JOSÉ ROLÓN; YANINA GHIGLIONE; GABRIELA TURK; MARÍA LAURA POLO; NATALIA LAUFER

San Francisco

Conferencia; 23rd International AIDS Conference (Virtual); 2020

Background: Children infected via perinatal transmission at the beginning of the HIV epidemic are now reaching adulthood and data on this population is scarce. HIV infection during the development of the immune system could be associated with irreversible immune damage, once adulthood is reached. Here, we aimed to evaluate the quality of the cellular immune response in perinatally-infected young adults.Methods: Three groups were enrolled in 2019 in an Argentinean public hospital: 1-study group (SG): 15 perinatally-HIV-infected young adults (20-30 years); 2-Age control group (CA): 12 young adults with HIV acquisition after 16 years (paired by age to SG); 3-Time-of-infection control group (CT): 14 adults (>40 years) paired to SG, by infection time. Blood samples were obtained at enrollment. Phenotype, immune-activation and senescence markers on NK and T-cells were assayed by flow cytometry. Data was analyzed using non-parametric statistics.Results: CharacteristicYoung adults non-perinatally infected (CA)Adults non-perinatally infected (CT)Perinatally infected young adults (SG)p-value (CA vs SG)p-value (CT vs SG)Female (n, %)2, 18.27, 5011, 73.30.00640.2035Nadir LTCD4+ count -cells/mm3- (median, IQR)313, 239-562.3132, 72-407412, 40-9300.85580.2299Current LTCD4+ count -cells/mm3- (median, IQR)672, 608-903653, 584-912774, 609-12490.66140.4082Current CD4/CD8 (median, IQR)0.74, 0.58-1.060.94, 0.7-1.420.8, 0.58-1.260.64030.4321ART duration (time since first ART initiation) -months- (median, IQR)44.3, 33.9-62.9219.5, 178.72-253.54208.8, 60.8-262.70.00010.0160Time between HIV diagnosis and first undetectable VL -months- (median, IQR)14.73, 5.62-38.2104.15, 74.66-190.72165.73, 144.1-215.570.00010.0447Time undetectable -months- (median, IQR)31.69, 27.02-47.21170.12, 115.46-230.10106.45, 65.82-164.550.00070.0291Age at time of study enrollment -years- (median, IQR)28.04, 26.39-30.0750.91, 47.59-57.624.77, 21.92-28.440.07340.0000The main characteristics of participants are described in Table-1. Despite similar LTCD4+ count and CD4/CD8 ratio, SG had higher frequency of naive LTCD4+ (44.4%, IQR:33.6-55.8) than CT (13.9%, IQR:3.4-25, p=0.0003) and CA (25.3%, IQR:9.3-37, p=0.01). Regarding naïve LTCD8, the higher frequency was observed in SG (29.3%, IQR:19.5-46.1) but it was only statistically different to CT (5.9%, IQR:1.9-9.9, p=0.001). LTCD4+, LTCD8+ and NK PD1 expression was lower in SG, being significantly different between LTCD4+PD1+ of SG and CT (27.7%, IQR:20.2-39.1 vs 43.4, IQR:30.4-59.4, p=0.016).Conclusions: Young adults,HIV perinatally-infected at the beginning of the epidemic in Argentina, had a history of more difficulties to achieve viral control. Nevertheless, and despite being undetectable for only a median of 8 years, these individuals exhibited a lower frequency of exhausted T-cells and NK-cells, and higher rates of naïve T-cells. These findings could reflect an adaptive response during the development of the immune system in the context of an immunosuppressive virus. Further analyses regarding immune functionality and reservoir composition in this special population are needed.