Integrase inhibitors in children and adolescents: clinical use and resistance.

BACKGROUND: Although integrase inhibitor (INI)-based regimens are now the first-line choice for all people living with HIV, experience among children and adolescents is still scarce. We describe the characteristics and outcomes of a paediatric/adolescent cohort on INI-based ART. METHODS: Retrospective analysis of HIV-infected patients below 18 years of age who started an INI-based regimen from 2007 to 2019, enrolled in the Spanish National Adult (CoRIS) and Paediatric (CoRISpe) cohorts. Resistance mutations were identified by the Stanford HIV Drug Resistance Database. RESULTS: Overall, 318 INI-based regimens were implemented in 288 patients [53.8% female; median age at start of 14.3 years (IQR 12.0-16.3)]. Most were born in Spain (69.1%), vertically infected (87.7%) and treatment-experienced (92.7%). The most frequently prescribed INI was dolutegravir (134; 42.1%), followed by raltegravir (110; 34.6%) and elvitegravir (73; 23.0%). The median exposure was 2.0 years (IQR 1.1-3.0). The main reasons to start an INI-based therapy were treatment simplification (54.4%) and virological failure (34.3%). In total, 103 (32.4%) patients interrupted their regimen: 14.5% for simplification and 8.5% due to virological failure. Most subjects who received dolutegravir (85.8%) and elvitegravir (83.6%) did not interrupt their regimen and maintained undetectable viral load. There were only five virological failures with dolutegravir and three with elvitegravir. There were no interruptions related to adverse events. Seven patients with virological failure presented major resistance mutations to INIs; none of them were on dolutegravir. CONCLUSIONS: INI-based regimens were effective and safe for HIV treatment in children and adolescents. Dolutegravir and elvitegravir presented an excellent profile, and most patients achieved and maintained viral suppression.

Significant differences between verbal and non-verbal intellectual scales on a perinatally HIV-infected cohort: from pediatrics to young adults.

Delayed neurodevelopment is a common outcome in perinatally HIV-infected children. Our aim was to assess the intellectual profile of our cohort, considering both the infection and socio-environmental related variables. A cross-sectional cohort study was undertaken at seven major hospitals in Spain belonging to the CoRISpeS cohort (n = 97). Patients were followed up according to a standard protocol. Intellectual measures, psychosocial profile and HIV infection-related data have been analysed. The average patient age was 15 years. The median CD4 cell percentage was 35% (1,59). Viral load was undetectable in 80% of the patients and 27% were on AIDS category; 38% of whom had encephalopathy. The average composite score of both crystallized intelligence (CI) and intelligence quotient (IQ) for the cohort was lower than that of the general population (p < 0.001). Results revealed a significant difference of 38% between crystallized and fluid intelligence. There was a clear association between IQ and age of diagnosis (p = 0.022); CI and CDC classification (p = 0.035), CD4 count (p = 0.011) and CD4 nadir (p = 0.001). Higher parental education was associated with better performance across all intelligence scales (p < 0.002). A regression model showed that CI was influenced by the academic level of caregivers (p = 0.002), age at start of cART (p = 0.050) and primary language (p = 0.058). Findings revealed significant differences in verbal and non-verbal intellectual scales resulting in a misleading IQ Composite score. Crystallized intelligence demonstrated the highest level of impairment despite adequate treatment and good immunovirological status, while fluid intelligence results were average. Caregiver level of education was the strongest factor across all intelligence measures.

Successful management of chronic multifocal Q fever Osteomyelitis with adjuvant interferon-gamma therapy.

We present a 3-year-old girl who had chronic recurrent multifocal osteomyelitis caused by Coxiella burnetii despite long-term dual antibiotic therapy. Excellent clinical response was achieved and sustained when immunomodulatory therapy with interferon-γ was initiated. This is the case of a first child who was successfully treated with interferon-γ as adjuvant therapy for chronic multifocal Q fever osteomyelitis.