Low unspliced cell-associated HIV RNA in early treated adolescents living with HIV on long suppressive ART.

Introduction: Initiation of antiretroviral treatment (ART) in patients early after HIV-infection and long-term suppression leads to low or undetectable levels of HIV RNA and cell-associated (CA) HIV DNA and RNA. Both CA-DNA and CA-RNA, overestimate the size of the HIV reservoir but CA-RNA as well as p24/cell-free viral RNA can be indicators of residual viral replication. This study describes HIV RNA amounts and levels of cytokines/soluble markers in 40 well-suppressed adolescents who initiated ART early in life and investigated which viral markers may be informative as endpoints in cure clinical trials within this population. Methods: Forty adolescents perinatally infected with HIV on suppressive ART for >5 years were enrolled in the CARMA study. HIV DNA and total or unspliced CA-RNA in PBMCs were analyzed by qPCR/RT-qPCR and dPCR/RT-dPCR. Cell-free HIV was determined using an ultrasensitive viral load (US-VL) assay. Plasma markers and p24 were analyzed by digital ELISA and correlations between total and unspliced HIV RNA and clinical markers, including age at ART, Western Blot score, levels of cytokines/inflammation markers or HIV CA-DNA, were tested. Results: CA-RNA was detected in two thirds of the participants and was comparable in RT-qPCR and RT-dPCR. Adolescents with undetectable CA-RNA showed significantly lower HIV DNA compared to individuals with detectable CA-RNA. Undetectable unspliced CA-RNA was positively associated with age at ART initiation and Western Blot score. We found that a higher concentration of TNF-α was predictive of higher CA-DNA and CA-RNA. Other clinical characteristics like US-VL, time to suppression, or percent CD4+ T-lymphocytes were not predictive of the CA-RNA in this cross-sectional study. Conclusions: Low CA-DNA after long-term suppressive ART is associated with lower CA-RNA, in concordance with other reports. Patients with low CA-RNA levels in combination with low CA-DNA and low Western Blot scores should be further investigated to characterize candidates for treatment interruption trials. Unspliced CA-RNA warrants further investigation as a marker that can be prioritized in paediatric clinical trials where the sample volume can be a significant limitation.

Infección congénita por CMV en recién nacidos hijos de madre con infección por VIH / Congenital cytomegalovirus infection in newborns born to HIV-infected mothers

Introducción: La infección congénita por CMV (CMVc) es más frecuente en hijos expuestos al. VIH durante la gestación, con tasas reportadas en la era pre-TAR del 2 al 7%. El control de la carga viral de VIH y la recuperación inmunológica asociada al tratamiento antirretroviral (TAR) podrían ser factores que influyan en su transmisión. El objetivo de este trabajo fue describir la epidemiología de la infección CMVc en recién nacidos expuestos al VIH en el Hospital Universitario 12 de Octubre, entre los años 2000-2017. Material y métodos: Estudio observacional y retrospectivo. Se recogieron variables epidemiológicas y clínicas a través de la historia clínica de los sujetos incluidos. Se realizó análisis estadístico con el programa informático SPSS 24.0. Resultados: Se incluyeron 288 pares de madres/hijos. Observamos una tasa de CMVc del 2,1% (IC 95% 0,7-4,9). Conclusiones: La tasa de CMVc fue menor a la comunicada en la era pre-TAR, aunque aún parece superior a la observada en niños no expuestos al VIH.(AU)

Introduction: Congenital citomegalovirus (CMVc) infection is more common in children exposed to HIV during pregnancy, with reported rates in pre-ART era from 2 to 7%. The use of combined antiretroviral treatment (ARTc) could be a determining factor in reducing this risk of CMV transmission. The aim of this study was to describe the epidemiology of CMVc infection in newborns of HIV-infected mothers at Hospital Universitario 12 de Octubre, Madrid, Spain, from 2000 to 2017. Material and methods: An observational and retrospective study was carried out. Epidemiological and clinical variables were collected. Statistical analysis was performed with the SPSS 24.0 computer program. Results: 288 mother–infant pairs were included in the study. We observed a CMVc rate of 2.1% (95% CI 0.9–4.9). Conclusions: The rate of CMVc in HIV-exposed children observed was lower than that reported in pre-ARTc era but seems higher than those described in general population.(AU)

Congenital cytomegalovirus infection in newborns born to HIV-infected mothers.

INTRODUCTION: Congenital citomegalovirus (CMVc) infection is more common in children exposed to HIV during pregnancy, with reported rates in pre-ART era from 2 to 7%. The use of combined antiretroviral treatment (ARTc) could be a determining factor in reducing this risk of CMV transmission. The aim of this study was to describe the epidemiology of CMVc infection in newborns of HIV-infected mothers at Hospital Universitario 12 de Octubre, Madrid, Spain, from 2000 to 2017. MATERIAL AND METHODS: An observational and retrospective study was carried out. Epidemiological and clinical variables were collected. Statistical analysis was performed with the SPSS 24.0 computer program. RESULTS: 288 mother-infant pairs were included in the study. We observed a CMVc rate of 2.1% (95% CI 0.9-4.9). CONCLUSIONS: The rate of CMVc in HIV-exposed children observed was lower than that reported in pre-ARTc era but seems higher than those described in general population.

Early ART initiation during infancy preserves natural killer cells in young European adolescents living with HIV (CARMA cohort).

INTRODUCTION: HIV infection causes pathological changes in the natural killer (NK) cell compartment that can be only partially restored by antiretroviral therapy (ART). We investigated NK cells phenotype and function in children with perinatally acquired HIV (PHIV) and long-term viral control (five years) due to effective ART in a multicentre cross-sectional European study (CARMA, EPIICAL consortium). The impact of age at ART start and viral reservoir was also evaluated. METHODS: Peripheral blood mononuclear cells (PBMCs) from 40 PHIV who started ART within two years of life (early treated patients (ET), ≤6 months; late treated patients (LT), > 6 months), with at least five years of HIV-1 suppression (<40 HIV copies/mL), were collected between November 2017 and August 2018. NK phenotype and function were analysed by flow cytometry and transcriptional profile of PBMCs by RNA-Seq. HIV-1 DNA was measured by real-time polymerase chain reaction (Data were analysed by Spearman correlation plots and multivariable Poisson regression model (adjusted for baseline %CD4 and RNA HIV viral load and for age at ART start as an interaction term, either ET or LT) to explore the association between NK cell parameters and HIV reservoir modulated by age at ART start. RESULTS: A significantly higher frequency of CD56neg NK cells was found in LT compared with ET. We further found in LT a positive correlation of CD56neg NK cells with HIV-1 DNA. LT also displayed increased expression of the NKG2D and NKp46 activating receptors and perforin compared with ET. Moreover, CD107a+ and IFN-γ+ frequencies in non-stimulated NK were associated with HIV-1 DNA in LT patients. Finally, RNA-Seq analysis showed in LT an up-regulation of genes related to NK-activating pathways and susceptibility to apoptosis compared with ET. CONCLUSIONS: We show that early initiation of ART during infancy preserves the NK compartment and is associated with lower HIV-1 reservoir. Such condition persists over adolescence due to long-term viral control achieved through effective ART.

Prevention and treatment of fetal cytomegalovirus infection with cytomegalovirus hyperimmune globulin: a multicenter study in Madrid.

INTRODUCTION: Cytomegalovirus (CMV) is the leading cause of congenital infection worldwide. Data about the management of CMV infection in pregnant women are scarce, and treatment options are very limited. The aim of the study is to investigate the effectiveness of cytomegalovirus hyperimmune globulin (CMV-HIG) for the prevention and treatment of congenital CMV (cCMV) infection. MATERIALS AND METHODS: A retrospective observational study was conducted in three tertiary hospitals in Madrid. In the period 2009-2015, CMV-HIG (Cytotect® CP Biotest, Biotest) treatment was offered to all pregnant women with primary CMV infection and/or detection of CMV-DNA in amniotic fluid in participating centers. Women were divided into prevention and treatment groups (PG and TG, respectively). Those with primary CMV infection who had not undergone amniocentesis comprised the PG and received monthly CMV-HIG (100 UI/kg). If CMV-DNA was subsequently detected in amniotic fluid, one extra dose of CMV-HIG (200 UI/kg) was given 4 weeks after the last dose. Those women were considered to be part of the PG group despite detection of CMV-DNA in amniotic fluid. In the case of a negative result in CMV-DNA detection in amniotic fluid or if amniocentesis was not performed, monthly HIG was given up to the end of the pregnancy. RESULTS: Thirty-six pregnant women were included. Median gestational age at birth was 39 weeks (interquartile range: 38-40) and two children (5.5%) were premature (born at 28 and 34 weeks' gestation). Amniocentesis was performed in 30/36 (83.4%) pregnancies and CMV PCR was positive in 21 of them (70%). One fetus with a positive PCR in amniotic fluid that received one dose of HIG after amniocentesis presented a negative CMV-PCR in urine at birth, and was asymptomatic at 12 months of age. Twenty-four children were infected at birth, and 16/21 (76.2%) presented no sequelae at 12 months, while two (9.5%) had a mild unilateral hearing loss and three (14.3%) severe hearing loss or neurological sequelae. Seventeen women were included in the PG and 19 in the TG. In the PG 7/17 (41%) fetuses were infected, one pregnancy was terminated due to abnormalities in cordocentesis and one showed a mild hearing loss at 12 months of age. In the TG, 18/19 children (95%) were diagnosed with cCMV, while the remaining neonate had negative urine CMV at birth. Eight out of the 19 fetuses (42.1%) showed CMV related abnormalities in the fetal US before HIG treatment. Complete clinical assessment in the neonatal period and at 12 months of age was available in 16 and 15 children, respectively. At birth 50% were symptomatic and at 12 months of age, 4/15 (26.7%) showed a hearing loss and 3/15 (20%) neurologic impairment. Fetuses with abnormalities in ultrasonography before HIG presented a high risk of sequelae (odds ratios: 60; 95%CI: 3-1185; p = .007). DISCUSSION: Prophylactic HIG administration in pregnant women after CMV primary infection seems not to reduce significantly the rate of congenital infection, but is safe and it could have a favorable effect on the symptoms and sequelae of infected fetuses. The risk of long-term sequelae in fetuses without US abnormalities before HIG is low, so it could be an option in infected fetuses with normal imaging. On the other hand, the risk of sequelae among infected fetuses with abnormalities in fetal ultrasonography before HIG despite treatment is high.

Infecciones durante oxigenación de membrana extracorpórea / Experience with infections in the use of extracorporeal membrane oxygenation

OBJETIVO: Identificar factores de riesgo asociados con el desarrollo de infecciones nosocomiales en pacientes pediátricos asistidos con oxigenación por membrana extracorpórea (ECMO). PACIENTES Y MÉTODOS: Se han revisado de forma retrospectiva los pacientes que han recibido asistencia en ECMO de enero de 2011 a diciembre de 2014. Se han recogido datos demográficos, sobre la asistencia y sobre las infecciones que aparecen durante dicha asistencia. RESULTADOS: En este periodo hubo 50 asistencias en ECMO. Veinte pacientes tuvieron 23 episodios de infección, de los que 16 fueron bacteriemias, siendo el microorganismo más frecuente el estafilococo coagulasa negativo (habiendo 2 casos de candidemia). En cuanto a los grupos de edad, el lugar y el tipo de canulación, la presencia de coagulopatía grave y la realización de intervenciones quirúrgicas durante la asistencia, ninguno de estos factores resultó un factor de riesgo de infección estadísticamente significativo. La duración media de soporte en ECMO fue significativamente mayor en los pacientes que tuvieron alguna infección (8,91 vs. 5,96 días; p = 0,039). No hubo diferencias significativas en cuanto a la estancia en la Unidad de Cuidados Intensivos Pediátricos ni en cuanto a la supervivencia. CONCLUSIONES: La incidencia de infección durante ECMO es muy alta y los pacientes que tienen una infección están asistidos un tiempo significativamente mayor, por lo que se deben instaurar medidas para prevenir la aparición de estas infecciones e intentar minimizar el tiempo de asistencia en ECMO

OBJECTIVE: To identify risk factors associated with infectious complications acquired by paediatric patients during extracorporeal life support (ECLS). PATIENTS AND METHODS: Patients under ECLS from January 2011 to December 2014 have been retrospectively reviewed and data on demographics, care and infectious complications were collected. RESULTS: There were 50 ECLS assistances in the study period, of which 20 patients had 23 infectious complications: 16 were bloodstream infections, with coagulase negative staphylococci being the predominant isolate (there were 2 cases of candidaemia). Age, site of cannulation procedure, cannulation site, severe coagulopathy, and surgical interventions during assistance were analysed as risk factors for infectious complications, but no significant differences were found. ECLS duration was significantly longer in patients with infectious complications (8.91 vs 5.91 days; P=.039). There were no significant differences as regards Paediatric Intensive Care Unit (PICU) stay, or in survival. CONCLUSIONS: Infectious complications during ECLS are very common, and ECLS duration is significantly longer in patients with infections. Measures should be put in place to prevent infectious complications and reduce time on ECLS

[Experience with infections in the use of extracorporeal membrane oxygenation]. / Infecciones durante oxigenación de membrana extracorpórea.

OBJECTIVE: To identify risk factors associated with infectious complications acquired by paediatric patients during extracorporeal life support (ECLS). PATIENTS AND METHODS: Patients under ECLS from January 2011 to December 2014 have been retrospectively reviewed and data on demographics, care and infectious complications were collected. RESULTS: There were 50 ECLS assistances in the study period, of which 20 patients had 23 infectious complications: 16 were bloodstream infections, with coagulase negative staphylococci being the predominant isolate (there were 2 cases of candidaemia). Age, site of cannulation procedure, cannulation site, severe coagulopathy, and surgical interventions during assistance were analysed as risk factors for infectious complications, but no significant differences were found. ECLS duration was significantly longer in patients with infectious complications (8.91 vs 5.91 days; P=.039). There were no significant differences as regards Paediatric Intensive Care Unit (PICU) stay, or in survival. CONCLUSIONS: Infectious complications during ECLS are very common, and ECLS duration is significantly longer in patients with infections. Measures should be put in place to prevent infectious complications and reduce time on ECLS.

Parálisis bilateral delVI par craneal como manifestación inicial de la meningitis meningocócica / Bilateral abducens nerve palsy as the initial clinical manifestation of meningococcal meningitis

No disponible

Disease disclosure, treatment adherence, and behavioural profile in a cohort of vertically acquired HIV-infected adolescents. NeuroCoRISpeS study.

UNLABELLED: Advances in care and antiretroviral treatment, improved life expectancy and quality of life in children with perinatally-acquired human immunodeficiency virus (HIV) infection. There is increasing interest in the chronic effects of growing up with HIV. The aim of this study was to assess the psychosocial, emotional and behavioural functioning in a cohort of perinatally-acquired HIV-infected adolescents. Data were obtained through semi-structured interviews and the Strengths and Difficulties Questionnaire (SDQ) for emotional and behavioural disorders screening. RESULTS: A total of 95 patients (58% women) were assessed with a median age of 15 years (11-19.1) and a median age at diagnosis of 1.7 years (0-12.2). The median CD4 count, at the inclusion, was 626 cells/mm(3) (132-998), with 34% (10-52%). Viral load was <50 copies/ml in 72% of patients. Eighty-one per cent knew their diagnosis and optimal adherence was achieved in 53%. Passive coping was reported in 58.4% of the adolescents. Only 7.7% of teenagers had a complete and adequate knowledge of their disease and only 18.2% had shared it with their friends. Six unwanted pregnancies occurred (11% of women). Most of them (90%) attended school but 60% had been held back one or more school years. Overall, SDQ scored a risk of behavioural and emotional problems in 24.5%. The report of behaviours associated with hyperactivity was high in 14.9% of the population and borderline in 18.1%. Adolescents with encephalopathy accounted for 44% of those whose total scores fell in either the abnormal and borderline ranges for emotional difficulties (p = .038). CONCLUSION: Perinatally-acquired HIV-infected adolescents showed significant psychosocial and behavioural health risks that should bring attention to prevention and health care programmes. An earlier disclosure to children could favour a better psychological adjustment and a better treatment adherence. Future studies are needed to assess the relationship between vertically acquired HIV-infection and hyperactivity.

Once-daily antiretroviral therapy in a cohort of HIV-infected children and adolescents.

We evaluated the evolution over time of once-daily antiretroviral therapy in HIV-infected children and its relationship with adherence. An increase on the prevalence of once-daily antiretroviral therapy was observed over time (from 0.9% in 2002 to 44.2% in 2011). There was no difference in adherence regarding once-daily or BID regimens in 2011. Adherence was related to age and pill burden.

Evaluación inicial del programa de prevención de la transmisión materno-infantil de la infección por el virus de la inmunodeficiencia humana en Guinea Ecuatorial / Initial evaluation of a programme to prevent mother-to-child transmission of human immunodeficiency virus infection in Equatorial Guinea

INTRODUCCIÓN: La prevalencia de la infección por el virus de la inmunodeficiencia humana (VIH) en gestantes en Guinea Ecuatorial (GE) es alta (7,3%). En 2008 se actualizó el protocolo de prevención de transmisión vertical (PTMH) de VIH para adaptarlo a las guías de la OMS vigentes. El objetivo de nuestro trabajo es describir las características y la evolución de los niños expuestos al VIH tras la introducción del protocolo. MÉTODOS: Estudio descriptivo retrospectivo de los hijos de madres con infección por VIH, en el Hospital Regional y Centro de Salud María Rafols en Bata (GE) seguidos desde junio de 2008 hasta noviembre de 2011. El diagnóstico de infección por VIH en los niños se basó en el protocolo de test rápidos serológicos. RESULTADOS: Se incluyeron 103 niños, y de ellos 47 eran varones. Un total de 53 pacientes (51%) completaron el seguimiento. Catorce niños (26%) fueron diagnosticados de infección por VIH (11 por diagnóstico presuntivo, 3 por persistencia de anticuerpos después de los 18 meses de vida). Seis niños (12%) fallecieron antes de un diagnóstico definitivo. El 52% de las madres recibieron tratamiento antirretroviral (TAR) durante el embarazo. La transmisión vertical en los niños cuyas madres recibieron TAR fue del 16% (3/19), frente al 43% (10/23) en los niños cuyas madres no lo recibieron (p = 0,05), y del 8% (1/13) en los niños cuyas madres recibieron TAR y el niño profilaxis posnatal (p < 0,05). CONCLUSIONES: En nuestra cohorte el cumplimiento del protocolo de PTMH ha sido todavía muy bajo. El tratamiento antirretroviral en mujeres embarazadas disminuyó la tasa de transmisión vertical, pero esta aún sigue siendo muy alta. Una elevada proporción de niños se perdieron durante el seguimiento, así que es prioritario desarrollar estrategias para evitarlo, así como medidas de diagnóstico virológico precoz

Background: The prevalence of human immunodeficiency virus (HIV)-iBACKGROUND: The prevalence of human immunodeficiency virus (HIV)-infected pregnant women in Equatorial Guinea (EG) has been reported as 7.3%. In 2008 an updated version of the PMTCT protocol was accepted according to the current WHO guidelines. The aim of this study was to describe the characteristics and outcome of children exposed to HIV after the introduction of the protocol. METHODS: A retrospective review was conducted on the clinical characteristics of the infants born to HIV-infected mothers in the Hospital Regional de Bata and Primary Health Care Centre Maria Rafols in Bata (EG) between June 2008 and November 2011. The diagnosis of HIV infection in children was based on rapid serology tests. RESULTS: A total of 103 children were included, of which 47 were males. Fifty three patients (51%) completed the follow-up (51%). Fourteen children (26%) were diagnosed with HIV infection (11 presumptive diagnosis, 3 due to persistence of antibodies at 18 months). Six children (12%) died before a definitive diagnosis. Just over than half (52%) of mothers received antiretroviral therapy (ART) during pregnancy. The transmission rate in children whose mothers received ART was 16% (3/19), compared with 43% (10/23) in children whose mothers did not receive it. Only one child was infected (8%) when the mother received ART, and child received postnatal prophylaxis. CONCLUSIONS: The PMTCT protocol compliance was still very low. Antiretroviral therapy in pregnant women decreased the rate of vertical transmission, but the rate still remains very high. Many children were lost to follow-up. Strategies to prevent loss to follow-up and methods for earlier virological diagnostic are needed

[Initial evaluation of a programme to prevent mother-to-child transmission of human immunodeficiency virus infection in Equatorial Guinea]. / Evaluación inicial del programa de prevención de la transmisión materno-infantil de la infección por el virus de la inmunodeficiencia humana en Guinea Ecuatorial.

BACKGROUND: The prevalence of human immunodeficiency virus (HIV)-infected pregnant women in Equatorial Guinea (EG) has been reported as 7.3%. In 2008 an updated version of the PMTCT protocol was accepted according to the current WHO guidelines. The aim of this study was to describe the characteristics and outcome of children exposed to HIV after the introduction of the protocol. METHODS: A retrospective review was conducted on the clinical characteristics of the infants born to HIV-infected mothers in the Hospital Regional de Bata and Primary Health Care Centre Maria Rafols in Bata (EG) between June 2008 and November 2011. The diagnosis of HIV infection in children was based on rapid serology tests. RESULTS: A total of 103 children were included, of which 47 were males. Fifty three patients (51%) completed the follow-up (51%). Fourteen children (26%) were diagnosed with HIV infection (11 presumptive diagnosis, 3 due to persistence of antibodies at 18 months). Six children (12%) died before a definitive diagnosis. Just over than half (52%) of mothers received antiretroviral therapy (ART) during pregnancy. The transmission rate in children whose mothers received ART was 16% (3/19), compared with 43% (10/23) in children whose mothers did not receive it. Only one child was infected (8%) when the mother received ART, and child received postnatal prophylaxis. CONCLUSIONS: The PMTCT protocol compliance was still very low. Antiretroviral therapy in pregnant women decreased the rate of vertical transmission, but the rate still remains very high. Many children were lost to follow-up. Strategies to prevent loss to follow-up and methods for earlier virological diagnostic are needed.

Infecciones neonatales por Staphylococcus aureus de inicio en la comunidad / Community-onset Staphylococcus aureus infection in neonates

Introducción Staphylococcus aureus es una causa importante de infecciones neonatales de inicio en la comunidad. En los últimos años se ha notificado en Estados Unidos la emergencia de infecciones por cepas resistentes a la meticilina en este grupo de edad, aunque existen pocos estudios en España. El objetivo de este estudio es describir las características epidemiológicas, clínicas y microbiológicas de las infecciones por S. aureus de inicio en la comunidad en neonatos. Métodos Estudio prospectivo de las infecciones neonatales por S. aureus de inicio en la comunidad realizado durante 3 años (2007-2009) en el Servicio de Urgencias Pediátricas del Hospital 12 de Octubre de Madrid (España).Resultado sSe registraron 30 casos de los que solo un aislado (3,3%) fue resistente a la meticilina y 2 (6,7%) fueron LPV(+).Conclusiones A pesar de la emergencia de SARM y/o productor de LPV fuera del ambiente hospitalario en población pediátrica en España, dichas infecciones son todavía poco frecuentes en neonatos (AU)

Introduction Staphylococcus aureus is a major cause of neonatal community-onset infections. The emergence of methicillin-resistant S. aureus infections in this age group has been reported in USA in the last few years; however there are no studies in Spain. The aim of this study is to describe the epidemiological, clinical and microbiological characteristics of S. aureus community-onset infections in neonates. Methods We prospectively reviewed the S. aureus infections in neonates over a three year period (2007-2009) in the Pediatric Emergency Department of Hospital 12 de Octubre in Madrid (Spain).ResultsWe recorded 30 cases of neonatal S. aureus community-onset infections. Only one isolated (3.3%) was resistant to methicillin, and two (6.7%) were PVL(+).Conclusions Despite the emergence of MRSA outside the hospital in pediatric population in Spain, CA-MRSA and SA PVL(+) infections are not frequent in neonates (AU)

[Community-onset Staphylococcus aureus infection in neonates]. / Infecciones neonatales por Staphylococcus aureus de inicio en la comunidad.

INTRODUCTION: Staphylococcus aureus is a major cause of neonatal community-onset infections. The emergence of methicillin-resistant S. aureus infections in this age group has been reported in USA in the last few years; however there are no studies in Spain. The aim of this study is to describe the epidemiological, clinical and microbiological characteristics of S. aureus community-onset infections in neonates. METHODS: We prospectively reviewed the S. aureus infections in neonates over a three year period (2007-2009) in the Pediatric Emergency Department of Hospital 12 de Octubre in Madrid (Spain). RESULTS: We recorded 30 cases of neonatal S. aureus community-onset infections. Only one isolated (3.3%) was resistant to methicillin, and two (6.7%) were PVL(+). CONCLUSIONS: Despite the emergence of MRSA outside the hospital in pediatric population in Spain, CA-MRSA and SA PVL(+) infections are not frequent in neonates.

Use of combination neonatal prophylaxis for the prevention of mother-to-child transmission of HIV infection in European high-risk infants.

OBJECTIVES: To evaluate use of combination neonatal prophylaxis (CNP) in infants at high risk for mother-to-child transmission (MTCT) of HIV in Europe and investigate whether CNP is more effective in preventing MTCT than single drug neonatal prophylaxis (SNP). DESIGN: Individual patient-data meta-analysis across eight observational studies. METHODS: Factors associated with CNP receipt and with MTCT were explored by logistic regression using data from nonbreastfed infants, born between 1996 and 2010 and at high risk for MTCT. RESULTS: In 5285 mother-infant pairs, 1463 (27.7%) had no antenatal or intrapartum antiretroviral prophylaxis, 915 (17.3%) had only intrapartum prophylaxis and 2907 (55.0%) mothers had detectable delivery viral load despite receiving antenatal antiretroviral therapy. Any neonatal prophylaxis was administered to 4623 (87.5%) infants altogether; 1105 (23.9%) received CNP. Factors significantly associated with the receipt of CNP were later calendar birth year, no elective caesarean section, maternal CD4 cell count less than 200 cells/µl, maternal delivery viral load more than 1000 copies/ml, no antenatal antiretroviral therapy, receipt of intrapartum single-dose nevirapine and cohort. After adjustment, absence of neonatal prophylaxis was associated with higher risk of MTCT compared to neonatal prophylaxis [adjusted odds ratio (aOR) 2.29; 95% confidence interval (95% CI) 1.46-2.59; P < 0.0001]. Further, there was no association between CNP and MTCT compared to SNP (aOR 1.41; 95% CI 0.97-2.5; P = 0.07). CONCLUSION: In this European population, CNP use is increasing and associated with presence of MTCT risk factors. The finding of no observed difference in MTCT risk between one drug and CNP may reflect residual confounding or the fact that CNP may be effective only in a subgroup of infants rather than the whole population of high-risk infants.