Trends in drug resistance prevalence in HIV-1-infected children in Madrid: 1993 to 2010 analysis.

BACKGROUND: Drug resistance mutations compromise antiretroviral treatment (ART) effectiveness in HIV-1-infected children. Trends in drug resistance prevalence have not been previously evaluated in HIV-infected children in Spain. METHODS: HIV-1 variants, drug resistance prevalence dynamics and drug susceptibility were analyzed from 1993 to 2010 in HIV-infected children with available pol sequence, sample or drug resistance profile. HIV-1 variants were characterized by phylogenetic analysis. Resistance mutations in pretreated and naive patients were identified according to International AIDS Society-2010 and the World Health Organization list, respectively. RESULTS: In 232 patients, genotypic resistance profiles (n = 11) or pol sequences (n = 128) were recovered or newly generated from infected samples (n = 93). Patients were mainly in care at pediatric units (63%), were mostly Europeans (84%), with moderate AIDS symptoms (65%), on ART (91%) and infected by HIV-1 subtype B (89%). Transmitted major drug resistance mutations were selected in 6 (13.6%) of the 44 ART-naive children: 4.8%, 9.3% and 11.6%, for protease inhibitors, nucleoside reverse transcriptase inhibitors and nonnucleoside reverse transcriptase inhibitors, respectively. Overall resistance prevalence was higher (71.8%) among ART-exposed children: 39.9%, 66.5% and 35.3% for protease inhibitors, nucleoside reverse transcriptase inhibitors and nonnucleoside reverse transcriptase inhibitors, respectively. Resistance prevalence among ART-exposed children was higher in 2009 to 2010 relative to 1993 to 1999 for nonnucleoside reverse transcriptase inhibitors (42% versus 6%; P = 0.006), protease inhibitors (39% versus 13%; P = 0.004) and nucleoside reverse transcriptase inhibitors (63% versus 44%; P = NS). Susceptibility to each drug in resistant viruses was predicted. The rate of non-B infections increased in the last years, mainly caused by recombinant viruses. CONCLUSIONS: The increasing resistance prevalence among the HIV-infected pediatric population in Spain highlights the importance of specific drug resistance and drug susceptibility surveillance in long-term pretreated children to optimize treatment regimens.

Complement factor I deficiency: a not so rare immune defect: characterization of new mutations and the first large gene deletion.

BACKGROUND: Complement Factor I (CFI) is a serine protease with an important role in complement alternative pathway regulation. Complete factor I deficiency is strongly associated with severe infections. Approximately 30 families with this deficiency have been described worldwide. PATIENTS AND METHODS: We have studied five new Spanish families suffering from CFI deficiency. From 19 screened people, 7 homozygous, 10 heterozygous and 2 healthy subjects were identified. Clinical, biochemical and genetic descriptions are included. RESULTS: Molecular studies demonstrated 4 novel mutations in the screened individuals; amongst them, we describe here the first great gene deletion reported in the CFI locus, which includes full exon 2 and part of the large intron 1. CONCLUSION: CFI deficiency is possibly an underestimated defect and the eventual existence of this deficiency should be tested in those patients exhibiting low C3 and recurrent bacterial infections. We propose a simple diagnostic flowchart to help clinicians in the identification and correct diagnosis of such patients.

Nuevos diagnósticos de infección VIH en niños / New diagnosis of HIV infection in children

Introducción En la cohorte de niños infectados de la Comunidad de Madrid ha aumentado el número de niños de procedencia extranjera en los últimos años. Los objetivos fueron evaluar las características epidemiológicas y clínicas en los nuevos diagnósticos y describir los diferentes subtipos del VIH-1.Pacientes y métodos Se analizaron los nuevos diagnósticos desde el año 1997, dividiéndolos en 3 periodos: P1 (1997-2000), P2 (2001-2004), P3 (2005-2009). Se analizó la procedencia según regiones geográficas y país de procedencia, las diferencias clínicas e inmunovirológicas así como respuesta al tratamiento. Se evaluó el subtipo genético del VIH-1 mediante análisis filogenético de los genes de proteasa y de la retrotranscriptasa. Resultados Se identificaron 141 nuevos diagnósticos de infección VIH, siendo el porcentaje de procedencia extranjera en P1 (22,5%), P2 (50%) y P3 (68%). La procedencia ha cambiado de Latinoamérica en P1 a África subsahariana en P3. No hubo diferencias de la media de edad al diagnóstico entre autóctonos y extranjeros, el estadio clínico CDC A/B/C, carga viral, porcentaje de CD4 al diagnóstico y actuales. Había una tendencia de mejor respuesta virológica en extranjeros tras el primer ciclo de TARGA (terapia antirretroviral de gran actividad) independiente del tratamiento recibido. Se obtuvieron 66 subtipos, el 24% eran subtipos no-B (56% formas recombinantes). Todos los subtipos de los autóctonos (43) y latinoamericanos (5) eran subtipos B, sin embargo, todos los niños procedentes de África Subsahariana (14) eran subtipos no-B. Conclusión No se encontraron diferencias entre niños infectados por VIH extranjeros o autóctonos, salvo los diferentes subtipos de VIH-1 (AU)

Introduction The number of children of immigrant origin in the last few years has increased the cohort of HIV-infected children in the Community of Madrid. The objectives of the study were to evaluate the epidemiological and clinical characteristics of the new diagnosed children and describe the different subtypes of HIV-1.Patients and methods The new diagnosed children were analysed from the year 1997, divided into 3 periods: P1 (1997-2000), P2 (2001-2004), P3 (2005-2009). The regions and countries of origin, the clinical, immune and viral characteristics, as well as the response to treatment were analysed. The subtypes of HIV-1 were evaluated by phylogenetic analysis of protease genes and reverse transcriptase. Results We identified 141 new diagnoses of HIV infection, the percentage of immigrant origin in P1 was (22.5%), P2 (50%) and P3 (68%). The origin had changed from Latin America in P1 to sub-Saharan Africa in P3. There were no differences between Spanish and immigrant children in the age at diagnosis, the CDC clinical stage A/B/C, viral load, percentage of CD4 at diagnosis and actual. Better viral response was more likely in immigrants after the first regimen of HAART (Highly active antiretroviral treatment) independently of the treatment received. A total of 66 subtypes were obtained, 24% were subtypes non-B (56% recombinants forms). All subtypes of Spanish children (43) and Latin American (5) were subtypes B, and all the children from sub-Saharan Africa (14) were subtypes non-B. Conclusion There were no differences between immigrants and Spanish children infected by HIV, except the different subtypes of HIV-1 (AU)

[New diagnosis of HIV infection in children]. / Nuevos diagnósticos de infección VIH en niños.

INTRODUCTION: The number of children of immigrant origin in the last few years has increased the cohort of HIV-infected children in the Community of Madrid. The objectives of the study were to evaluate the epidemiological and clinical characteristics of the new diagnosed children and describe the different subtypes of HIV-1. PATIENTS AND METHODS: The new diagnosed children were analysed from the year 1997, divided into 3 periods: P1 (1997-2000), P2 (2001-2004), P3 (2005-2009). The regions and countries of origin, the clinical, immune and viral characteristics, as well as the response to treatment were analysed. The subtypes of HIV-1 were evaluated by phylogenetic analysis of protease genes and reverse transcriptase. RESULTS: We identified 141 new diagnoses of HIV infection, the percentage of immigrant origin in P1 was (22.5%), P2 (50%) and P3 (68%). The origin had changed from Latin America in P1 to sub-Saharan Africa in P3. There were no differences between Spanish and immigrant children in the age at diagnosis, the CDC clinical stage A/B/C, viral load, percentage of CD4 at diagnosis and actual. Better viral response was more likely in immigrants after the first regimen of HAART (Highly active antiretroviral treatment) independently of the treatment received. A total of 66 subtypes were obtained, 24% were subtypes non-B (56% recombinants forms). All subtypes of Spanish children (43) and Latin American (5) were subtypes B, and all the children from sub-Saharan Africa (14) were subtypes non-B. CONCLUSION: There were no differences between immigrants and Spanish children infected by HIV, except the different subtypes of HIV-1.

Lichtheimia corymbifera subcutaneous infection successfully treated with amphotericin B, early debridement, and vacuum-assisted closure.

Lichtheimia corymbifera (syn. Absidia corymbifera, Mycocladus corymbifer) is an ubiquitous cosmopolitan mold that can cause primary cutaneous and deep tissue infection in healthy individuals. We report a subcutaneous L. corymbifera infection in a 13-year-old immune-competent child, with a severe traumatic injury, with a successful outcome after early diagnosis and treatment with lipid amphotericin B, early debridement, and vacuum-assisted closure (VAC).