[This corrects the article DOI: 10.3389/fimmu.2022.947549.].

Introduction: The vertical transmission rate (VTR) of HIV has decreased to less than 2% in high income countries., in spite of which perinatal infections continue to occur. We present data from the national cohort of pregnant women living with HIV and their children in Spain. objectives were to describe the characteristics of this population, evaluate the VTR of HIV, safety of antiretroviral therapy (ART) and the prevalence of coinfection. Patients and methods: Multicentre prospective, observational and descriptive study with ticipation of 62 hospitals. The sample included pegnant women living with HIV whose children were born between January 2020 and December 2022. We collected prospective data on characteristics of mothers and children using an online questionnaire (REDCap web application). Results: The study included 414 mother-child dyads. Most mothers were immigrants (227/349; 65.1%). The main route of HIV infection was heterosexual transmission (160/402; 39.8%), followed by vertical transmission (44/402; 10.9%). The diagnosis was made before conception in313/389 women (80.4%), 394/402 (98%) received ART during pregnancy and 356/402 (89.3%) had an undetectable viral load at the time of delivery. The delivery was vaginal 230/388 children (59.3%). The proportion of preterm birth was 11.1%. The most frequent neonatal prophylaxis approach was monotherapy with zidovudine (358/414; 86.5%). There were cases of vertical transmission of HIV (95% CI, 0%-1.54%). Only one newborn was breastfed. Conclusions: At present, most women living with HIV in Spain receive the diagnosis before conception, are of foreign ancestry and achieve good control of the infection. Although VTR is very low in Spain, there are still infections that could be prevented with early diagnosis and treatment. (c) 2024 Asociacion Espanola ola de Pediatr& imath;a. Published by Elsevier Espana, a, S.L.U. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/ 4.0/).

Introduction The frequency of mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) in Latin America has decreased considerably. However, new infections continue to be recorded, and the pediatric population remains one of the most vulnerable groups in this region. The main objective of the study was to describe the clinical, epidemiological and psychosocial characteristics of new diagnoses of HIV MTCT in 2018 in the PLANTAIDS network (Paediatric Network for Prevention, Early Detection and Treatment of HIV in Children) during the 3 years following diagnosis. Methodology Retrospective, multicenter, descriptive study based on a 3-year follow-up of patients diagnosed with HIV infection due to MTCT in 2018 in 10 hospitals in 8 Latin American countries (Costa Rica, Ecuador, Mexico, Honduras, El Salvador, Panama, Guatemala and Venezuela). The hospitals belonged to the PLANTAIDS network, which is included in CYTED (Ibero-American Programme of Science and Technology for Development). Results The study population comprised 72 pediatric patients (38.9% male). The median age at diagnosis was 2.4 years (IQR: 0.8–5.4). There were 35 cases of opportunistic infections corresponding to 25 patients (34.7%), with tuberculosis being the most common. Adequate childhood vaccination coverage was achieved in 80.5%. There were 3 cases of acute SARS-CoV-2 infection, and these were asymptomatic or mildly symptomatic. According to the Centers for Disease Control and Prevention (CDC) classification, the most frequent clinical-immunological stage at all check-ups was C1. Three patients died from opportunistic infections and/or advanced HIV infection. Conclusions It is important to diagnose HIV infection early in pediatrics, since early initiation of ART is associated with a decrease in mortality. Despite this, HIV infection has a poor prognosis in children, necessitating adequate follow-up to ensure adherence to health care and ART, although it can sometimes prove difficult in children.

Introducción La tasa de transmisión materno-infantil (TMI) del virus de la inmunodeficiencia humana (VIH) ha disminuido a menos del 2% en países desarrollados, a pesar de lo cual siguen produciéndose infecciones. Se presentan los datos de la Cohorte Nacional Española de mujeres embarazadas que viven con VIH y sus hijos. Los objetivos fueron describir sus características, evaluar la TMI de VIH, la seguridad del tratamiento antirretroviral (TAR) y la prevalencia de coinfecciones. Pacientes y métodos Estudio descriptivo, observacional, prospectivo y multicéntrico con participación de 62 hospitales. Se incluyeron las embarazadas cuyos hijos nacieron entre enero de 2020-diciembre de 2022. Se recogieron prospectivamente características de las madres y niños en REDCap. Resultados Hubo 414 pares madre-niño. Las madres fueron migrantes 227/349 (65,1%). La principal vía de adquisición del VIH fue la heterosexual (160/402; 39,8%), seguido de la TMI (44/402; 10,9%). En 313/389 (80,4%) el diagnóstico fue previo al embarazo, 394/402 (98%) recibieron TAR durante la gestación y 356/402 (89,3%) presentaba carga viral indetectable al parto. Hubo 230/388 (59,3%) neonatos nacidos por parto vaginal. La tasa de prematuridad fue 11,1%. La profilaxis neonatal más empleada (358/414; 86,5%) fue monoterapia con zidovudina (AZT). Hubo tres casos de TMI del VIH (0,72% intervalo de confianza [IC] 95%; 0-1,54%), todos ellos con infección intraútero. Todos menos uno recibieron lactancia artificial. Conclusiones Actualmente, las mujeres que viven con VIH en nuestro medio son migrantes, diagnosticadas mayoritariamente antes de la gestación y logran una adecuada situación inmunovirológica. Aunque la tasa de TMI es muy baja en nuestro país continúan ocurriendo infecciones prevenibles con diagnóstico y tratamiento más precoces.

Torque teno virus (TTV) viral load (VL), a component of the human virome, increases during immune suppression or dysregulation. This study aimed to explore TTV VL in youths living with vertically acquired HIV (YWVH) and its potential as an immunovirological marker. We performed an observational, retrospective study involving YWVH under antiretroviral treatment (ART) from the Spanish Cohort of HIV-infected children, adolescents, and vertically HIV-infected patients transferred to Adult Units (CoRISpe-FARO), compared to HIV-negative healthy donors (HD). Plasma TTV VL was assessed by qPCR. T-cell phenotype was analysed on cryopreserved peripheral blood mononuclear cells by flow cytometry. Correlations with baseline CD4 and CD8 and long-term virological evolution were examined. A total of 57 YWVH were compared with 23 HD. YWVH had a median CD4 T-cells of 736 cells/mm(3) [IQR: 574-906], a median of 17 years [IQR: 14-20.5] since ART initiation, and 65 months [IQR: 39-116] under HIV-RNA virological control. TTV VL was higher among YWVH and in males compared with females (p < 0.05). Among YWVH, TTV VL correlated with CD4 and CD8 counts and the CD4/CD8 ratio (p = 0.002; r = - 0.39, p = 0.037; r = 0.277, p = 0.005; r = - 0.37 respectively). TTV VL correlated with activation expression markers (HLA-DR+/CD38+) on CD4 (p = 0.007, r = 0.39) and the soluble proinflammatory cytokine IL-6 (p = 0.006, r = 0.38).

This study aimed to analyse the long-term effect of direct-acting antivirals (DAAs) in vertically acquired HIV/HCV-coinfected youths. We performed a multicentre, longitudinal and observational study within the Spanish Cohort of HIV-infected children and adolescents and vertically HIV-infected patients transferred to Adult Units (CoRISpe-FARO). We included HIV/HCV-coinfected youths (n = 24) that received DAAs between 2015 and 2017 with successful sustained viral response (SVR) with a subsequent follow-up of at least three years. Long-term evolution in liver disease severity and haematologic markers, lipid and immune profiles after SVR were assessed. Study times were the start date of DAAs treatment (baseline, T0) and 1, 2, 3, 4 and 5 years after SVR (T1, T2, T3, T4 and T5, respectively). We observed global improvements in liver function data that persist over time and a favourable haematologic and immune outcome at the long-term including a constant augment in leucocytes, neutrophils, neutrophils to lymphocytes ratio (NLR) and CD4/CD8 ratio over-time. Regarding the lipid profile, we found a significant increase in total cholesterol T2, total cholesterol/high-density lipoprotein (HDL) ratio at T4, triglycerides at T5, low-density lipoprotein (LDL) over time, and a decrease in HDL in all patients but with marked higher levels in the subgroup receiving anti-HIV Protease Inhibitor (PI)-based regimens. Comparisons of vertically HIV/HCV-coinfected youths after SVR at 3-year follow-up and a control group of vertically HIV-monoinfected youths never infected by HCV showed no significant differences in most variables analysed, suggesting a possible normalization in all parameters.

PURPOSE:We aimed to assess IgG antibodies against the SARS-CoV-2 spike protein (anti-SARS-CoV-2 S IgG) in vaccinated mothers and their infants at delivery and 2-3 months of age. METHODS:We conducted a prospective study on mothers who received at least one dose of the COVID-19 vaccine (Pfizer-BNT162b2, Moderna mRNA-1273, or Oxford-AstraZeneca ChAdOx1-S) during pregnancy and on their infants. The baseline was at the time of delivery (n = 93), and the end of follow-up was 2 to 3 months post-partum (n = 53). Serum anti-SARS-CoV-2 S IgG titers and ACE2 binding inhibition levels were quantified by immunoassays. RESULTS:Mothers and infants had high anti-SARS-CoV-2 S IgG titers against the B.1 lineage at birth. However, while antibody titers were maintained at 2-3 months post-partum in mothers, they decreased significantly in infants (p < 0.001). Positive and significant correlations were found between anti-SARS-CoV-2 S IgG titers and ACE2-binding inhibition levels in mothers and infants at birth and 2-3 months post-partum (r > 0.8, p < 0.001). Anti-S antibodies were also quantified for the Omicron variant at 2-3 months post-partum. The antibody titers against Omicron were significantly lower in mothers and infants than those against B.1 (p < 0.001). Again, a positive correlation was observed for Omicron between IgG titers and ACE2-binding inhibition both in mothers (r = 0.818, p < 0.001) and infants (r = 0.386, p < 0.005). Previous SARS-CoV-2 infection and COVID-19 vaccination near delivery positively impacted anti-SARS-CoV-2 S IgG levels. CONCLUSIONS:COVID-19 mRNA vaccines induce high anti-SARS-CoV-2 S titers in pregnant women, which can inhibit the binding of ACE2 to protein S and are efficiently transferred to the fetus. However, there was a rapid decrease in antibody levels at 2 to 3 months post-partum, particularly in infants.

It is known that SARS-CoV-2 antibodies from pregnant women with SARS-CoV-2 infection during pregnancy cross the placenta but the duration and the protective effect of these antibodies in infants is scarce. This prospective study included mothers with SARS-COV-2 infection during pregnancy and their infants from April 2020 to March 2021. IgG antibodies to SARS-CoV-2 spike protein were performed on women and infants at birth and at two and six months during follow-up. Anthropometrical measures and physical and neurological examinations and a clinical history of symptoms and COVID-19 diagnosis were collected. Simple linear regression was performed to compare categorical and continuous variables. To compare the mother’s and infant’s antibody titers evolution, a mixed linear regression model was used. A predictive model of newborn antibody titers at birth has been established by means of simple stepwise linear regression. 51 mother-infant couples were included. 45 (90

Background: The vertical transmission of severe acute respiratory coronavirus-2 (SARS-CoV-2) remains highly debated. Here, we evaluated SARS-CoV-2-transmission in newborns with intrauterine conditions. Methods: This was a prospective, observational and multicentric study involving 13 Spanish hospitals included in the GEStational and NEOnatal-COVID cohort. Pregnant women with microbiologically confirmed SARS-CoV-2 infection during any trimester of pregnancy or delivery and their newborns were included from March to November 2020. Demographic, clinical and microbiological data were also obtained. Viral loads were analyzed in different maternal and newborn biological samples (placenta, breast milk and maternal blood; urine, meconium and newborn blood). Results: A total of 177 newborns exposed to SARS-CoV-2 were included. Newborns were tested by reverse transcriptase-polymerase chain reaction using nasopharyngeal swabs within the first 24–48 hours of life and at 14 days of life. In total 5.1% were considered to have SARS-CoV-2 infection in the neonatal period, with 1.7% considered intrauterine and 3.4% intrapartum or early postnatal transmission cases. There were no differences in the demographic and clinical characteristics of the pregnant women and their newborns’ susceptibility to infections in their perinatal history or background. Conclusions: Intrauterine transmission of SARS-CoV-2 is possible, although rare, with early postnatal transmission occurring more frequently. Most infected newborns remained asymptomatic or had mild symptoms that evolved well during follow-up. We did not find any maternal characteristics predisposing infants to neonatal infection. All infected newborn mothers had acute infection at delivery. Although there was no presence of SARS-CoV2 in cord blood or breast milk samples, SARS-CoV-2 viral load was detected in urine and meconium samples from infected newborns.

SARS-CoV2 infection in pregnancy and exposed newborns is poorly known. We performed a longitudinal analysis of immune system and determined soluble cytokine levels in pregnant women infected with SARS-CoV2 and in their newborns. Women with confirmed SARS-CoV2 infection and their exposed uninfected newborns were recruited from Hospital General Universitario Gregorio Marañón. Peripheral blood mononuclear cells (PBMCs), cord cells and plasma were collected at birth and 6 months later. Immunophenotyping of natural killer (NK), monocytes and CD4/CD8 T-cells were studied in cryopreserved PBMCs and cord cells by multiparametric flow cytometry. Up to 4 soluble pro/anti-inflammatory cytokines were assessed in plasma/cord plasma by ELISA assay. SARS-CoV2-infected mothers and their newborns were compared to matched healthy non-SARS-CoV2-infected mothers and their newborns. The TNFα and IL-10 levels of infected mothers were higher at baseline than those of healthy controls. Infected mothers showed increased NK cells activation and reduced expression of maturation markers that reverted after 6 months. They also had high levels of Central Memory and low Effector Memory CD4-T cell subsets. Additionally, the increased CD4- and CD8-T cell activation (CD154 and CD38) and exhaustion (TIM3/TIGIT) levels at baseline compared to controls remained elevated after 6 months. Regarding Treg cells, the levels were lower at infected mothers at baseline but reverted after 6 months. No newborn was infected at birth. The lower levels of monocytes, NK and CD4-T cells observed at SARS-CoV2-exposed newborns compared to unexposed controls significantly increased 6 months later. In conclusion, SARS-CoV2 infection during pregnancy shows differences in immunological components that could lead newborns to future clinical implications after birth. However, SARS-CoV2 exposed 6-months-old newborns showed no immune misbalance, whereas the infected mothers maintain increased activation and exhaustion levels in T-cells after 6 months.

OBJECTIVE:The prevalence of subclinical liver abnormalities is high among people with HIV, but data regarding perinatally HIV-infected children and adolescents (PHIV) are scarce. Noninvasive image techniques offer an opportunity to address nonalcoholic fatty liver disease (NAFLD) in a population in which the scores validated for adults have not been tested. DESIGN:Prospective cross-sectional study including PHIV and uninfected controls. METHODS:Noninvasive imaging techniques for the diagnosis of NAFLD and/or fibrosis were performed, and four scores to predict NAFLD were evaluated. RESULTS:Seventy-six participants (59.2% women) with a median of 19 years old (interquartile range: 15.5-25.6) were included, 38 were PHIV and 38 were age and sex-matched controls. All HIV participants were on ART at the moment of inclusion, and 86.8% were virologically suppressed. A total of 11 PHIV and three controls were diagnosed with NAFLD (28.9% vs. 7.9%; P = 0.02) by noninvasive imaging techniques. The performance of scores based on clinical and analytical parameters was very poor. Although nonsignificant, overweight was more common among participants with NAFLD, who had a significantly higher BMI. Differences in HIV-related parameters between the groups were nonsignificant, except for the CD4+/CD8+ T-cells ratio, decreased among PHIV diagnosed with NAFLD (P = 0.04). CONCLUSIONS:The prevalence of NAFLD was high (28.9%) among PHIV, and only partially explained by overweight and metabolic syndrome defining factors. The scores based on clinical and analytical parameters did not accurately identify participants at risk. Therefore, liver ultrasound assessment should be considered for the screening of NAFLD among PHIV in routine clinical practice.

Background: An increasing number of women living with perinatally acquired HIV are reaching adulthood and becoming pregnant. Achieving viral suppression is challenging in this population frequently exposed to numerous antiretroviral regimens. This study describes the long-term outcomes of pregnant women living with perinatally acquired HIV in Spain. Methods: Descriptive, retrospective, multicenter study of the women living with perinatally acquired HIV who gave birth between January 2000 and December 2019 in Madrid. Epidemiological, clinical, and HIV-related data were collected from the first delivery to the end of the study period, including antiretroviral therapy, prevention strategies, and outcomes. Results: Sixty-three live births in 33 women were included. The mean number of pregnancies per women was 1.9 (range: 1-6). At first delivery, women's median age was 20 years (interquartile range: 18-23), 11 (33.3%) had been previously diagnosed with AIDS and 6 (18%) with mental health disorders. Forty percent became pregnant unsuppressed, whereas 81% achieved viral suppression at delivery. Treatment interruptions were common after delivery, as were losses to follow-up, with no positive effect of pregnancy on retention to care or the immune virological situation. Five women (15%) experienced a new AIDS event, and there were 2 deaths (6%) during follow-up. There was 1 case of mother-to-child transmission in a nonadherent woman in whom preventive measures could not be implemented. Conclusions: Pregnancy in this unique population of women living with perinatally acquired HIV poses particular challenges. Specific strategies, including a multidisciplinary approach, are needed to minimize perinatal transmission risks and improve outcomes during the postpartum period.

Multicenter study designed to describe epidemiologic and clinical characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive cases registered among children and adolescents living with HIV (CALWH). SARS-CoV-2 infection was confirmed in 13.3% of CALWH, with all patients presenting mild symptoms, and the outcome was good in all patients. None of the HIV- and antiretroviral treatment-related variables studied were associated with greater infection risk or could be considered protective.

Carrasco, Itzíar; Olveira, Antonio; Lancharro, Ángel; Escosa, Luis; Mellado, María José; Busca, Carmen; Montes, María Luisa; Díez, Cristina; Alcolea-Ruiz, Sonia; Navarro, María Luisa; Sáinz, Talía Author Information

INTRODUCTION:Pregnant women are vulnerable to severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection. Neutralizing antibodies against the SARS-CoV-2 spike (S) protein protect from severe disease. This study analyzes the antibody titers to SARS-CoV-2 S protein in pregnant women and their newborns at delivery, and six months later. METHODS:We conducted a prospective study on pregnant women with confirmed SARS-CoV-2 infection and newborns. Antibody (IgG, IgM, and IgA) titers were determined using immunoassays in serum and milk samples. An angiotensin-converting enzyme 2 (ACE2) receptor-binding inhibition assay to the S protein was performed on the same serum and milk samples. RESULTS:At birth, antibodies to SARS-CoV-2 spike protein were detected in 81.9% of mothers' sera, 78.9% of cord blood samples, and 63.2% of milk samples. Symptomatic women had higher antibody titers (IgG, IgM, and IgA) than the asymptomatic ones (P < 0.05). At six months postpartum, IgG levels decreased drastically in children's serum (P < 0.001) but remained high in mothers' serum. Antibody titers correlated positively with its capacity to inhibit the ACE2-spike protein interaction at baseline in maternal sera (R2  = 0.203; P < 0.001), cord sera (R2  = 0.378; P < 0.001), and milk (R2  = 0.564; P < 0.001), and at six months in maternal sera (R2  = 0.600; P < 0.001). CONCLUSIONS:High antibody levels against SARS-CoV-2 spike protein were found in most pregnant women. Due to the efficient transfer of IgG to cord blood and high IgA titers in breast milk, neonates may be passively immunized to SARS-CoV-2 infection. Our findings could guide newborn management and maternal vaccination policies.

AbstractBackgroundImportant prevention efforts have led to a reduction in mother-to-child transmission of HIV (MTCT) globally. However, new cases of paediatric HIV infections still occur. Early diagnosis of new HIV infections is essential to start an appropriate antiretroviral treatment to avoid childhood morbidity and mortality related to infection. The aim of this study was to describe the new cases of MTCT in Latin-American referral hospitals.MethodsA retrospective, multicentre and descriptive study of the new cases of MTCT diagnosed during 2018 in 13 referral hospitals from 8 Latin-American countries (Costa Rica, Ecuador, El Salvador, Guatemala, Honduras, Mexico, Nicaragua, and Panama) belonging to PLANTAIDS (Paediatric Network for Prevention, Early Detection and Treatment of HIV in Children), was conducted. PLANTAIDS is included in CYTED (Ibero-American Programme of Science and Technology for Development).ResultsEighty-one children (40.7% males) were included, median age at diagnosis of 2.33 years (IQR:0.7–4.7). Less than 3% of women knew their HIV diagnosis before pregnancy. More than 80% of them were diagnosed after delivery, 8.7% during pregnancy, and 2.9% at delivery. Only one patient underwent antiretroviral therapy (ART) prior to pregnancy. At diagnosis, 50.0% of the children presented with an advanced stage of disease (stage C following the current CDC classification for HIV infection), and 34.4% had less than 15% CD4+cells/mm3. The time elapsed between delivery and the maternal diagnosis was correlated with the age of children at diagnosis, ρ = 0.760,p < 0.001. Younger age at diagnosis (p = 0.03), a smaller number of previous hospitalizations (p < 0.01), and better immunovirological status (p < 0.01) were found in children whose mothers knew their HIV status at delivery, compared to mothers who were not aware of it.ConclusionsAlthough MTCT in Latin America has declined in recent years, our series shows there are still cases that indicate some failures in prevention, being a critical point to improve an earlier diagnosis of pregnant women. Half of the children were diagnosed in an advanced stage of disease and the delay in maternal diagnosis entailed a worse clinical and immunological child’ prognosis.

Background: The vertical transmission of severe acute respiratory coronavirus-2 (SARS-CoV-2) remains highly debated. Here, we evaluated SARS-CoV-2-transmission in newborns with intrauterine conditions. Methods: This was a prospective, observational and multicentric study involving 13 Spanish hospitals included in the GEStational and NEOnatal-COVID cohort. Pregnant women with microbiologically confirmed SARS-CoV-2 infection during any trimester of pregnancy or delivery and their newborns were included from March to November 2020. Demographic, clinical and microbiological data were also obtained. Viral loads were analyzed in different maternal and newborn biological samples (placenta, breast milk and maternal blood; urine, meconium and newborn blood). Results: A total of 177 newborns exposed to SARS-CoV-2 were included. Newborns were tested by reverse transcriptase-polymerase chain reaction using nasopharyngeal swabs within the first 24-48 hours of life and at 14 days of life. In total 5.1% were considered to have SARS-CoV-2 infection in the neonatal period, with 1.7% considered intrauterine and 3.4% intrapartum or early postnatal transmission cases. There were no differences in the demographic and clinical characteristics of the pregnant women and their newborns' susceptibility to infections in their perinatal history or background. Conclusions: Intrauterine transmission of SARS-CoV-2 is possible, although rare, with early postnatal transmission occurring more frequently. Most infected newborns remained asymptomatic or had mild symptoms that evolved well during follow-up. We did not find any maternal characteristics predisposing infants to neonatal infection. All infected newborn mothers had acute infection at delivery. Although there was no presence of SARS-CoV2 in cord blood or breast milk samples, SARS-CoV-2 viral load was detected in urine and meconium samples from infected newborns.

BACKGROUND:Children living with HIV are reaching adulthood and transitioning to adult clinics. This study aimed to describe clinical and immunovirological status after transition in patients with perinatal HIV.METHODS:Patients participating in the Spanish multicenter pediatric HIV cohort (CoRISpe) transferred to adult care (FARO cohort) from 1997 to 2016 were included. Clinical and immunovirological data were collected from 12 years old to the last follow-up moment after transition (up to December 2017). We used mixed-effect models to analyze changes in CD4 counts or viral suppression and multivariate analysis for risk factors for virological failure (VF) and immune status after transition. Transition years were classified into 5-year periods.RESULTS:Three hundred thirty-two youths were included. The median age at transition was 18 years (interquartile range: 16.3-18.9) and 58.1% women. The median follow-up time after transition was 6.6 years (interquartile range: 4.6-9.8), and 11 patients (3.3%) died. The immunovirological status at transition improved over the last periods. Globally, VF decreased from 27.7% at transition to 14.4% at 3 years post-transition (P < 0.001), but no changes were observed in the last 2 transition periods. There were no significant differences in CD4 over the transition period. Risk factors for VF after transition were female sex, being born abroad and VF at transition, and for lower CD4 after transition were Romani heritage, younger age at transition, lower CD4 nadir, and CD4 at transition.CONCLUSIONS:After transition, virological suppression improved in the early transition periods, and immunological status remained stable. Nevertheless, some patients had higher risk of worse outcomes. Identifying these patients may aid during transition.

Introduction: After the introduction of combination antiretroviral treatment, (ART) mortality in HIV-infected patients has dramatically decreased. However, it is still high in patients at risk, as adolescents transitioning to adult care (AC) without virologic control. The aim of this study was to characterize mortality and comorbidities of perinatally infected HIV (PHIV) patients after transition to AC. Methods: A multicenter retrospective study from patients included in the CoRISpe-FARO Spanish cohort was conducted. PHIV patients who died after transition to AC between 2009 and 2019 were included. Clinical, immunovirologic characteristics, treatments received, comorbidities and causes of death were described. Results: Among 401 PHIV patients, 14 died (3.5%). All were Spanish, 11/14 (78.6%) women. The median age at diagnosis was 1.5 years (interquartile range [IQR] 0.5–3.9), at transfer to AC was 18 years [16.1–19.9] and at death was 25.8 years [23.6–27.1]. In pediatric units [pediatric care (PC)], CD4+ nadir was 85 cells/μL [IQR 9.7–248.5] and 6/14 patients were classified as C-clinical stage. During AC, all patients were on C-clinical stage and CD4+ nadir dropped to 11.5 cells/μL [4.5–43.3]. cART adherence was extremely poor: in PC, 8/14 patients registered voluntary treatment interruptions; only one had undetectable VL at transition. In AC, 12/14 patients stopped treatment 2 or more periods of time. All deaths were related to advanced HIV disease. Mental health disorders were observed in 7/14 (50%). Main complications described: recurrent bacterial infections (57.1%), wasting syndrome (42.9%), esophageal candidiasis (28.6%) and Pneumocystis jirovecii pneumonia (28.6%). Four women had 11 pregnancies; 5 children were born (none infected). Conclusions: Young adults PHIV infected who transition to AC without virologic suppression or proven ability to adhere to ART are at high risk of mortality. Mortality was noted as a consequence of advanced HIV disease, frequent mental health problems and poor adherence to ART.

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.