Successful antiretroviral therapy (ART) has dramatically reduced mortality among HIV-infected children. However, there is growing concern about long-term effects associated to ART. The aim of this study was to determine the prevalence of metabolic abnormalities in a cohort of perinatally HIV-infected adolescents and young adults and to identify associated factors. We present results from a cross-sectional analysis including individuals 12 to 20 years of age, from a prospective, longitudinal cohort of perinatally-acquired HIV-infected children, adolescents and young adults in Madrid. Clinical and immunological data were recorded and complete lipid and glycemic profiles were determined. Ninety-nine adolescents were included, with a median age of 15.3 years [13.6-16.7]. Patients with abnormal levels of lipids were as follows: 27.2% total cholesterol ≥200 mg/dl, 25.9% LDL cholesterol (LDL-c) ≥ 130 mg/dl, 14.1% HDL-C < 35 mg/dl and 39.8% triglycerides ≥ 150 mg/dl. Current use of protease inhibitors (PI) was associated with higher triglyceride values (p = 0.022). Four (4.6%) patients showed fasting glucose ≥ 100 mg/dl and 30.6% presented with insulin resistance (IR) (HOMA-IR over the 90th centile). In the multivariate logistic regression analysis adjusted for sex, age, weight, Tanner stage, protease inhibitors (PI) and nucleoside reverse transcriptase inhibitors (NRTI) treatment length and CD4 nadir, IR was associated with higher waist circumference Z score; OR: 3.92(CI95%: 1.15-13.4) (p = 0.03). There was a high prevalence of insulin resistance and lipid abnormalities in this cohort of perinatally-acquired HIV-infected adolescents. A simple clinical measurement like waist circumference Z score might be a reliable marker and predictor of insulin resistance in these patients.

Pertussis immunization during pregnancy results in high pertussis antibody concentrations in young infants but may interfere with infant immune responses to post-natal immunization. This phase IV, multi-country, open-label study assessed the immunogenicity and safety of infant primary vaccination with DTaP-HepB-IPV/Hib and 13-valent pneumococcal conjugate vaccine (PCV13). Enrolled infants (6-14 weeks old) were born to mothers who were randomized to receive reduced-antigen-content diphtheria-tetanus-three-component acellular pertussis vaccine (Tdap group) or placebo (control group) during pregnancy (270/7-366/7 weeks' gestation) with crossover immunization postpartum. All infants received 2 or 3 DTaP-HepB-IPV/Hib and PCV13 doses according to national schedules. Immunogenicity was assessed in infants pre- and 1 month post-primary vaccination. The primary objective was to assess seroprotection/vaccine response rates for DTaP-HepB-IPV/Hib antigens 1 month post-primary vaccination. 601 infants (Tdap group: 296; control group: 305) were vaccinated. One month post-priming, seroprotection rates were 100% (diphtheria; tetanus), ≥98.5% (hepatitis B), ≥95.9% (polio) and ≥94.5% (Hib) in both groups. Vaccine response rates for pertussis antigens were significantly lower in infants whose mothers received pregnancy Tdap (37.5-77.1%) versus placebo (90.0-99.2%). Solicited and unsolicited adverse event rates were similar between groups. Serious adverse events occurred in 2.4% (Tdap group) and 5.6% (control group) of infants, none were vaccination-related. Pertussis antibodies transferred during pregnancy may decrease the risk of pertussis infection in the first months of life but interfere with the infant's ability to produce pertussis antibodies, the clinical significance of which remains unknown. Safety and reactogenicity results were consistent with previous experience. ClinicalTrials.gov: NCT02422264.

Aims: The gut microbiota exerts a critical influence in the immune system. The gut microbiota of human virus immunodeficiency (HIV)-infected children remains barely explored. We aimed to characterize the fecal microbiota in vertically HIV-infected children and to explore the effects of its modulation with a symbiotic nutritional intervention. Methods: a pilot, double blind, randomized placebo-controlled study including HIV-infected children who were randomized to receive a nutritional supplementation including prebiotics and probiotics or placebo for four weeks. HIV-uninfected siblings were recruited as controls. The V3–V4 region of the 16S rRNA gene was sequenced in fecal samples. Results: 22 HIV-infected children on antiretroviral therapy (ART) and with viral load (VL) <50/mL completed the follow-up period. Mean age was 11.4 ± 3.4 years, eight (32%) were male. Their microbiota showed reduced alpha diversity compared to controls and distinct beta diversity at the genus level (Adonis p = 0.042). Patients showed decreased abundance of commensals Faecalibacterium and an increase in Prevotella, Akkermansia and Escherichia. The nutritional intervention shaped the microbiota towards the control group, without a clear directionality. Conclusions: Vertical HIV infection is characterized by changes in gut microbiota structure, distinct at the compositional level from the findings reported in adults. A short nutritional intervention attenuated bacterial dysbiosis, without clear changes at the community level. Summary: In a group of 24 vertically HIV-infected children, in comparison to 11 uninfected controls, intestinal dysbiosis was observed despite effective ART. Although not fully effective to restore the microbiota, a short intervention with pre/probiotics attenuated bacterial dysbiosis.

Aims: Children with HIV exhibit chronic inflammation and immune dysfunction despite antiretroviral therapy (ART). Strategies targeting persistent inflammation are needed to improve health in people living with HIV. The gut microbiota likely interacts with the immune system, but the clinical implications of modulating the dysbiosis by nutritional supplementation are unclear. Methods: Pilot, double-blind, randomized placebo-controlled trial in which 24 HIV-infected on ART were randomized to supplementation with a daily mixture of symbiotics, omega-3/6 fatty acids and amino acids, or placebo four weeks, in combination with ART. We analyzed inflammatory markers and T-cell activation changes and their correlations with shifts in fecal microbiota. Results: Twenty-four HIV-infected children were recruited and randomized to receive a symbiotic nutritional supplement or placebo. Mean age was 12 ± 3.9 years, 62.5% were female. All were on ART and had HIV RNA < 50/mL. We did not detect changes in inflammatory (IL-6, IL-7, IP-10), microbial translocation (sCD14), mucosal integrity markers (IFABP, zonulin) or the kynurenine to tryptophan ratio, or changes in markers of the adaptive immune response in relation to the intervention. However, we found correlations between several key bacteria and the assessed inflammatory and immunological parameters, supporting a role of the microbiota in immune modulation in children with HIV. Conclusions: In this exploratory study, a four-week nutritional supplementation had no significant effects in terms of decreasing inflammation, microbial translocation, or T-cell activation in HIV-infected children. However, the correlations found support the interaction between gut microbiota and the immune system.

Group A Streptococcus (GAS) can cause a broad array of clinical manifestations and complications. Recently, in post COVID-19 postpandemic months, there has been an increased incidence and severity of invasive infections in the pediatric age group in Spain and other European countries with high morbidity, affecting mostly to young children, associated with seasonal peaks in incidence of viral respiratory pathogens. The increased in incidence and severity has not been associated with predominant GAS strains, but rather to the lack of immunity to both GAS and common viral respiratory infections due to isolation measures to prevent COVID-19. Due to the nonspecific initial clinical manifestations a high index of suspicion is necessary in order to initiate a prompt medical and surgical treatment when necessary to improve the outcome. Prevention strategies are needed as well as continuous microbiological surveillance of iGAS strains.

Integrase inhibitor (INSTI) with boosted darunavir (DRV/r), a regimen with a high-resistance barrier, avoiding NRTI toxicities, might be a switching option in children living with HIV (CLWHIV). SMILE is a randomised non-inferiority trial evaluating safety and antiviral efficacy of once-daily INSTI + DRV/r vs. continuing on current standard-of-care (SOC) triple ART (2NRTI + boosted PI/NNRTI) in virologically-suppressed CLWHIV aged 6-18 years. The primary outcome is the proportion with confirmed HIV-RNA ≥50 copies/mL by week 48, estimated by Kaplan-Meier method. Non-inferiority margin was 10%. Registration number for SMILE are: ISRCTN11193709, NCT #: NCT02383108. Between 10th June 2016 and 30th August 2019, 318 participants were enrolled from Africa 53%, Europe 24%, Thailand 15% and Latin America 8%, 158 INSTI + DRV/r [153 Dolutegravir (DTG); 5 Elvitegravir (EVG)], 160 SOC. Median (range) age was 14.7 years (7.6-18.0); CD4 count 782 cells/mm³ (227-1647); 61% female. Median follow-up was 64.3 weeks with no loss to follow-up. By 48 weeks, 8 INSTI + DRV/r vs. 12 SOC had confirmed HIV-RNA ≥50 copies/mL; difference (INSTI + DRV/r-SOC) -2.5% (95% CI: -7.6, 2.5%), showing non-inferiority. No major PI or INSTI resistance mutations were observed. There were no differences in safety between arms. By week 48, difference (INSTI + DRV/r-SOC) in mean CD4 count change from baseline was -48.3 cells/mm³ (95% CI: -93.4, -3.2; p = 0.036). Difference (INSTI + DRV/r-SOC) in mean HDL change from baseline was -4.1 mg/dL (95% CI: -6.7, -1.4; p = 0.003). Weight and Body Mass Index (BMI) increased more in INSTI + DRV/r than SOC [difference: 1.97 kg (95% CI: 1.1, 2.9; p < 0.001), 0.66 kg/m² (95% CI: 0.3, 1.0; p < 0.001)]. In virologically-suppressed children, switching to INSTI + DRV/r was non-inferior virologically, with similar safety profile, to continuing SOC. Small but significant differences in CD4, HDL-cholesterol, weight and BMI were observed between INSTI + DRV/r vs. SOC although clinical relevance needs further investigation. SMILE data corroborate adult findings and provide evidence for this NRTI-sparing regimen for children and adolescents. Fondazione Penta Onlus, Gilead, Janssen, INSERM/ANRS and UK MRC. ViiV-Healthcare provided Dolutegravir.