Innate and adaptive abnormalities in youth with vertically acquired HIV through a multicentre cohort in Spain

Abstract

Introduction: Immune abnormalities have been described among youth with vertically acquired HIV (YWVH) despite antiretroviral treatment (ART). The CD4/CD8 ratio could be a useful prognostic marker. We assess immune activation and senescence in a cohort of YWVH in comparison to youth without vertically acquired HIV. Methods: YWVH under suppressive ART were included and compared to a group of HIV-negative donors (HD) matched by age and sex, from September 2019 to September 2020. Subset distribution and expression of activation, maturation, senescence and exhaustion markers on T and NK cells were studied on peripheral blood mononuclear cells by multiparametric flow cytometry. Results: Thirty-two YWVH (median age: 24.4 years (interquartile range: 22.5 to 28.3 years)) were included. Among YWVH, CD4-and CD8-T cells showed high levels of activation (HLA-DR/CD38), IL-7 receptor expression (CD127) and exhaustion (TIM-3). Regarding NK cells, YWVH showed increased levels of activation and exhaustion markers compared to HD. Strong inverted correlations were observed between T-cell activation (HLA-DR/CD38), senescence (CD57) and exhaustion (TIGIT, PD-1) levels with the CD4/CD8 ratio among YWVH. HLA-DR, CD69, NKG2D and NKG2A expression levels on NK cells also correlated with the CD4/CD8 ratio. Age at ART initiation was directly associated with higher frequency of CD16 high NK-cell subsets, exhaustion T-cell levels (CD57, TIM3) and NK cells activation levels. Conclusions: Immunological changes associated with vertically acquired HIV, characterized by increased activation and exhaustion levels in innate and adaptive immune components, are only partially restored by ART. The CD4/CD8 ratio can be a useful marker of disease progression for routine clinical practice.

SARS-CoV-2 Infection in Children and Adolescents Living With HIV in Madrid

“…Symptoms related to SARS-CoV-2 were predominately cough/rhinorrhea, followed by fever, similar to previously published data in healthy children 6 , 7 with a similar rate of complications. Despite the deleterious effects of HIV on the immune system of vertically infected patients, including chronic inflammation and immunoactivation, 8 our results do not suggest that HIV infection since birth in patients with good immunovirological control leads to a greater risk of SARS-CoV-2 morbidity.…”

Targeting the Gut Microbiota of Vertically HIV-Infected Children to Decrease Inflammation and Immunoactivation: A Pilot Clinical Trial

“…It is well known that HIV-infected children present persistent immune dysfunction despite early antiretroviral treatment (ART) [ 1 , 2 , 3 , 4 ]. Among adult populations, recent studies have pointed out the potential influence of the microbiome [ 5 , 6 , 7 , 8 ].…”

“…Different interventions aimed at mitigating the complex HIV-related gut-associated lymphoid tissue defects have been attempted to reduce the long-term consequences of chronic inflammation, mostly among adults [ 9 , 10 ]. Still, the effects of long-term immune abnormalities in the context of vertical infection are barely understood [ 1 , 4 ].…”

Nutritional Supplementation to Increase Influenza Vaccine Response in Children Living With HIV: A Pilot Clinical Trial

“…Despite achieving and maintaining viral suppression under antiretroviral treatment (ART), immunological restoration is not complete during HIV infection (1). Persistent inflammation and immunoactivation have been described both among adults and children and are a matter of concern (1)(2)(3). In HIVinfected children, innate and adaptive abnormalities (2) probably contribute to the reduction in the magnitude and durability of vaccine response (4)(5)(6)(7).…”

“…Persistent inflammation and immunoactivation have been described both among adults and children and are a matter of concern (1)(2)(3). In HIVinfected children, innate and adaptive abnormalities (2) probably contribute to the reduction in the magnitude and durability of vaccine response (4)(5)(6)(7). This impaired immunity leads to an increased rate of vaccine-preventable diseases in this population, greater severity and high progression-rate of vaccine-preventable infections, from measles to pneumococcal disease (8)(9)(10)(11).…”