Lipid and glucose alterations in perinatally-acquired HIV-infected adolescents and young adults.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Birth defects in a cohort of infants born to HIV-infected women in Spain, 2000-2009.

BACKGROUND: Antiretroviral therapy (ART) in pregnancy has resulted in a marked impact on reducing the risk of mother-to-child transmission (MCT) of HIV. However the safety of in utero ART exposure in newborns remains a concern. METHODS: A multicenter prospective observational study of HIV-infected mother and their infants was performed in Madrid, Spain, from 2000 to 2009. Children had regular visits with clinical examination according to protocol until the age of 24 months. An abdominal ultrasound and an echocardiogram were scheduled during follow up. Birth defects (BDs) were registered according to European Surveillance of Congenital Anomalies (EUROCAT). RESULTS: A total of 897 live births from 872 mothers were included. Overall the birth defects prevalence observed was 6.9% (95% CI 5.4-9.1).The most commonly reported birth defects types were in genital organs and urinary system (19 cases, 30.6%) and cardiovascular system (17 cases, 27.4%). There was no increased risk for infants exposed in the first trimester to ARVs compared with unexposed infants. No significant associations were observed between exposure to any individual antiretroviral agent during pregnancy and birth defects CONCLUSION: A higher prevalence of BDs was observed, higher than previously reported. In utero exposure to ART was not proved to be a major risk factor of birth defects in infants. However the relatively small number of patients is a major limitation of this study.

Metabolic disorders in vertically HIV-infected children: future adults at risk for cardiovascular disease.

BACKGROUND: Despite metabolic disorders in HIV-infected children being widely described, there is still a lack of agreed criteria for diagnoses and management. Numerous studies are coming from other settings and results are heterogeneous when assessing several analytical and clinical parameters. OBJECTIVES: To describe the prevalence of metabolic disorders and associated risk factors in the Spanish National cohort of HIV-infected pediatric patients (CoRISpe). METHODS: This was a cross-sectional study following all vertically HIV-infected children and adolescents in three referral centers included in the CoRISpe. Metabolic data (fasting lipids, glucose and insulin levels and thyroid hormone levels) were collected. Fat distribution was clinically assessed by expert clinicians. RESULTS: We included 157 patients [median age 13 years, interquartile range (IQR) 10-16]. Median duration of antiretroviral therapy was 10.2 years (IQR 5.0-13.0). Almost 20% of patients had insulin resistance and this was associated with hepatitis C co-infection, current use of stavudine (d4T) and hypertriglyceridemia. Hypercholesterolemia and hypertriglyceridemia were found in 23.9% and 24.8% of patients and were associated with current use of protease inhibitors (p = 0.042 and p = 0.022, respectively). Abnormal fat distribution was observed in 63 patients (40.5%): lipoatrophy in 32 (20.4%), lipohypertrophy in eight (5.1%) and a mixed pattern in 23 patients (14.6%), and it was significantly associated with previous exposure to stavudine (p < 0.001). CONCLUSIONS: Metabolic disorders are a significant problem in our HIV-infected pediatric population. We need to encourage the development of global strategies and the creation of consensus guidelines that can decrease the cardiovascular risk in this population.

Congenital syphilis, case report and epidemiologic features in Spain.

Congenital syphilis (CS) is a preventable disease. Nevertheless, since the year 2000, there has been an upward trend in incidence in Spain, similar to what has occurred in other European countries. We present a case of early congenital syphilis showing the classical features of the disease, in which skin lesions gave the clue that led to the diagnosis.

[Plasma antiretroviral levels in children with human immunodeficiency virus infection. Influence of sex and age]. / Niveles plasmáticos de antirretrovirales en niños con infección por el virus de la inmunodeficiencia humana. Influencia del género y de la edad.

INTRODUCTION: Pharmacologic studies have shown a relationship between plasma antiretroviral levels and toxicity/viral activity. Nevertheless, pharmacokinetic and pharmacodynamic data are inconsistent and limited in HIV-infected children. An analysis was performed of plasma antiretroviral concentrations in clinical practice and their influence on therapy efficacy in HIV-infected children. METHODS: Observational, prospective, multicenter study, including HIV-infected children followed up at 5 reference hospitals between March 2006 and June 2008. Pre-dose plasma antiretroviral levels were determined and the relationships with various clinical and analytical variables were investigated. RESULTS: A total of 129 patients were included, and 41.3% had antiretroviral plasma levels outside the established range. No differences were found between sexes. Children younger than 1 year had a higher rate of suboptimal levels and higher viral load than the remaining children. CONCLUSION: Antiretroviral plasma concentrations are more frequently suboptimal in children younger than 1 year. This finding is related with greater viral failure and implies a considerable challenge in this population, which requires very long-term treatment.

Low Bone Mineral Density in Vertically HIV-infected Children and Adolescents: Risk Factors and the Role of T-cell Activation and Senescence.

BACKGROUND: Our aim was to determine the prevalence and risk factors associated with low bone mineral density (BMD) in vertically HIV-infected patients and to investigate whether low BMD is related to immune activation and senescence induced by HIV infection. METHODS: A cross-sectional study was performed in 98 vertically HIV-infected patients. BMD was measured by dual-energy radiograph absorptiometry at lumbar spine. Height adjustment of BMD Z score was performed using height-for-age Z score. T-cell immune activation and senescence were analyzed in a subgroup of 54 patients by flow cytometry. RESULTS: Median age was 15.9 years, 71.4% were Caucasian, 99% received antiretroviral therapy and 80.6% had undetectable viral load. Low BMD (BMD Z score ≤ -2) was present in 15.3% of cases, but after height adjustment in 4.1% of cases. Height-adjusted BMD Z score was positively correlated with body mass index Z score, CD4/CD8 ratio and nadir CD4, and inversely with duration of severe immunosuppression and parathyroid hormone values. In the multivariate model including age, gender, ethnicity, encephalopathy, Tanner stage, nadir CD4, duration of viral suppression, CD4 count, CD4/CD8 ratio, body mass index, cumulative duration of antiretroviral therapy, tenofovir and protease inhibitors exposure, nadir CD4 was independently associated to height-adjusted BMD Z score. No association was found between height-adjusted BMD Z score and T-cell activation or senescence. CONCLUSIONS: The prevalence of low BMD in vertically HIV-infected patients was low after height adjustment. Nadir CD4, but not T-cell activation or senescence, was an independent predictor for low BMD. Larger and prospective studies are needed to achieve better knowledge of the pathogenesis of low BMD in vertical HIV infection.

Clinical outcomes improve with highly active antiretroviral therapy in vertically HIV type-1-infected children.

Background. Use of antiretroviral therapy has resulted in a decrease in morbidity and mortality rates in human immunodeficiency virus type 1 (HIV-1)-infected children.Methods. We performed a retrospective study involving 427 children to determine the effectiveness of different antiretroviral therapy protocols on clinical outcome. The follow-up period was divided into 5 calendar periods (CPs): CP1 (1980-1989), before antiretroviral therapy was administered; CP2 (1990-1993), when monotherapy was administered; CP3 (1994-1996), when combined therapy was administered; CP4 (1997-1998), when /=60% of children were receiving HAART.Results. Children experienced a progressive increase in the CD4(+) cell count and decrease in the viral load from 1997 onwards. A lower number of AIDS cases and deaths occurred during CP5 than during the other CPs (P<.01), with a relative risk of an absence of AIDS of >20 and a relative risk of survival of >30. The AIDS rate was >50% in CP1; we observed a very strong decrease to 14% in CP2, to 16% in CP3, to 7% in CP4, and to 2% in CP5. The mortality rates in CP2 and CP3 were >6% and thereafter decreased to 0.5% in CP5. The relative risks for no hospital admission in CP4 and CP5 were >3.5. The total rates of hospital admission in CP1, CP2, and CP3 were >30%; we observed a decrease in CP4 and CP5. The duration of hospitalization decreased during the follow-up period, and it was higher in CP1 (~30 days) than in the other periods.Conclusions. We observed that HAART produces a decrease in adverse clinical outcomes (i.e., hospital admission, AIDS, and death) in children with vertical HIV-1 infection in Madrid, Spain.

Low immunologic response to highly active antiretroviral therapy in naive vertically human immunodeficiency virus type 1-infected children with severe immunodeficiency.

We conducted a retrospective study to analyze the CD4 recovery of naive vertically human immunodeficiency virus-infected children with severe immunodeficiency who were followed up during at least 4 years of receiving highly active antiretroviral therapy (HAART). Children with baseline CD4 of <15% did not reach a mean CD4 of > or =25% after the 4th year on HAART. We conclude that starting HAART after severe immunosuppression of naive HIV-infected children may not be effective for recovery of normal %CD4.

Effects of highly active antiretroviral therapy with nelfinavir in vertically HIV-1 infected children: 3 years of follow-up. Long-term response to nelfinavir in children.

BACKGROUND: Antiretroviral treatment (ART) in children has special features and consequently, results obtained from clinical trials with antiretroviral drugs in adults may not be representative of children. Nelfinavir (NFV) is an HIV-1 Protease Inhibitor (PI) which has become as one of the first choices of PI for ART in children. We studied during a 3-year follow-up period the effects of highly active antiretroviral therapy with nelfinavir in vertically HIV-1 infected children. METHODS: Forty-two vertically HIV-infected children on HAART with NFV were involved in a multicentre prospective study. The children were monitored at least every 3 months with physical examinations, and blood sample collection to measure viral load (VL) and CD4+ cell count. We performed a logistic regression analysis to determinate the odds ratio of baseline characteristics on therapeutic failure. RESULTS: Very important increase in CD4+ was observed and VL decreased quickly and it remained low during the follow-up study. Children with CD4+ <25% at baseline achieved CD4+ >25% at 9 months of follow-up. HIV-infected children who achieved undetectable viral load (uVL) were less than 40% in each visit during follow-up. Nevertheless, HIV-infected children with VL >5000 copies/ml were less than 50% during the follow-up study. Only baseline VL was an important factor to predict VL control during follow-up. Virological failure at defined end-point was confirmed in 30/42 patients. Along the whole of follow-up, 16/42 children stopped HAART with NFV. Baseline characteristics were not associated with therapeutic change. CONCLUSION: NFV is a safe drug with a good profile and able to achieve an adequate response in children.

Safety and antiviral response at 12 months of lopinavir/ritonavir therapy in human immunodeficiency virus-1-infected children experienced with three classes of antiretrovirals.

INTRODUCTION: Many human immunodeficiency virus type 1 (HIV-1)-infected children have already failed treatment with 2 or even 3 classes of antiretrovirals. Coformulation of lopinavir with low dose ritonavir exhibits a potent antiretroviral effect. However, the data in heavily pretreated children are still scarce. This study evaluated the safety and effectiveness of combination therapy including lopinavir/ritonavir in children with prior exposure to all classes of oral antiretrovirals. METHODS: This was an open label multicenter observational study, in which data were reviewed according to a standardized protocol. The study population included all HIV-1-infected children with virologic failure (HIV-1 RNA >5000 copies/mL) followed in 12 Spanish hospitals for >12 months, experienced with the 3 classes of oral antiretrovirals, in whom a lopinavir/ritonavir-containing regimen was started. RESULTS: By March 2003, 45 patients had been treated with lopinavir/ritonavir for a median of 18 months (range, 3-28). The median age at baseline was 9.7 years (range, 4.3-17.1). The median times of prior treatment were 88 months (range, 31-145) with nucleoside reverse transcription inhibitors and 42 months (range, 19-63) with protease inhibitors. Twenty-five patients were classified as Centers for Disease Control and Prevention clinical category C. Median values for absolute and percentage CD4 at baseline were 501 (range, 6-1512) and 19% (range, 0.5-49), respectively, and plasma HIV-RNA was 5.0 log10 copies/mL (range, 4.1-6.1). During follow-up, 11 (24%) children switched from liquid to solid formulation. At 48 weeks, the median values for absolute and percentage CD4 increased by 199 cells/microL and 3%, respectively, and median plasma viral load declined 1.75 log10 copies/mL. Forty-two percent of children achieved a plasma RNA of <400 copies/mL (intent to treat analysis). Baseline genotypic resistance was available in 40 children. Nonresponders had 7.0 +/- 1.6 protease inhibitor-associated mutations at baseline compared with 4.8 +/- 1.7 in children achieving virologic suppression (P = 0.06). Adverse events were described in 18 children. Three children permanently discontinued and 4 transiently withdrew lopinavir/ritonavir. At 12 months, there were mild but not significant increases in plasma cholesterol and triglycerides. CONCLUSIONS: Lopinavir/ritonavir when given as part of salvage regimen is well-tolerated, although switching to pills is frequently required. The regimen has a potent and durable antiretroviral activity in most heavily pretreated children, despite the presence of multiple mutations to all classes of oral antiretrovirals.

Cardiac function in vertically HIV-infected children and adolescents in the era of highly active antiretroviral therapy.

BACKGROUND: Previous studies have demonstrated increased risk of adverse cardiac outcomes in adults with HIV infection. However, few studies have addressed this problem in vertically HIV-infected children and adolescents, and the long-term cardiac health of this unique population in the antiretroviral therapy era is still unknown. METHODS: Ventricular function was evaluated cross-sectionally in a group of HIV-infected children and adolescents and healthy controls, using conventional echocardiography along with tissue Doppler imaging and strain analysis by speckle tracking. Simultaneously, measurements of carotid intima-media thickness were performed. RESULTS: A total of 64 cases and 58 controls were included, mean age was 13.6 ± 5.4 years and 64% were females. All but 2 patients were on antiretroviral treatment, and 64% had undetectable viral load. HIV-infected patients showed higher intima-media thickness (0.425 ± 0.019 vs. 0.415 ± 0.019 mm, P = 0.003). Statistically significant differences were found between groups in ejection fraction and fractional shortening (66.1% and 36.2% in the HIV-infected group vs. 71.5% and 40.8% in the control group, respectively, P = 0.001), although individual values fell within or near normal ranges. There were no significant differences in diastolic function, tissue Doppler imaging or cardiac strain (longitudinal and rotational) between both groups. No associations were identified between echocardiographic parameters and current CD4+ T-lymphocyte counts, CD4+ T-lymphocyte nadir, HIV viral load, duration or type of antiretroviral treatment regimens. CONCLUSIONS: In a context of highly effective antiretroviral treatment, no differences were found regarding cardiac abnormalities using conventional and advanced ultrasound imaging techniques in this cohort of vertically HIV-infected children and adolescents, when compared with healthy controls.

Efficacy and safety of stavudine plus didanosine in asymptomatic HIV-infected children with plasma HIV RNA below 50,000 copies per milliliter.

BACKGROUND: Simple antiretroviral drug combinations might provide a comparable benefit to standard triple regimens in patients with mild HIV disease, because poor adherence and toxicities often compromise the sustained benefit of the latest triple regimens, especially when protease inhibitors are used. Bad adherence is the main cause of virological failure in HIV-positive children. The activity and safety of a double combination of nucleosides with high genetic barrier for resistance (stavudine plus didanosine) was assessed in children with nonadvanced HIV disease. METHOD: From February 1998 to March 1999, 16 children were enrolled in six Spanish hospitals in a trial in which didanosine (180 mg/m2/day) and stavudine (2 mg/Kg/day) were administered for 48 weeks to asymptomatic naive children with plasma HIV RNA below 50,000 copies/mL and CD4 counts above 15%. Genotypic resistance to nucleoside analogues was examined at baseline and at the end of the study. RESULTS: At baseline, median age was 6.5 years (range, 2-14). The absolute and percentage mean CD4 counts were 864 and 32%, respectively (z score: -0.48 and -1.1). Mean plasma viral load was 4.05 log. No clinical events occurred during the 1-year study period. Minor side effects were recorded in two thirds of children, although none led to drug discontinuation. Lipoatrophy was not recognized in any of the participants. Plasma HIV RNA below 400 copies/mL was reached by 43% and 44% of patients at 24 and 48 weeks, respectively. The z score for absolute and percentage CD4 count increased significantly at 48 weeks (+0.63 and +0.97, respectively) in respect to baseline (p <.05). Resistance mutations linked to didanosine (L74V or M184V) or stavudine (V75T) were not recognized and neither were multinucleoside resistant genotypes (151 complex or 69 inserts). However, four children developed AZT-like mutations T215Y and/or M41L. CONCLUSION: Treatment with a dual combination of didanosine plus stavudine in naive children with nonadvanced HIV disease is safe and provides a satisfactory virological outcome at 1 year. Toxicity and drug resistance seem to occur rarely when this combination is used, which allows good adherence and spares other future treatment options.

Cardiovascular biomarkers in vertically HIV-infected children without metabolic abnormalities.

Early cardiovascular disease is a major concern for ART-suppressed vertically HIV-infected children; however, evidence is lacking regarding specific preventive measures. In this study, a complete panel of biomarkers was determined together with carotid intima-media thickness (IMT), in a cohort of 64 HIV-infected children and 30 controls. Mean age of participants was 14.1±5 years. HIV-infected patients showed normal lipid profile, with only slightly higher triglycerides, and no differences between groups were found regarding IMT. HIV-infected patients displayed higher levels of soluble CD14 (sCD14) and soluble vascular cell adhesion molecule-1 (sVCAM) (all p<0.05). However, levels of C-reactive protein, interleukin-6, myeloperoxidase, monocyte chemoattractant protein-1, P-selectin and tissue plasminogen activator were similar between groups. Vertically HIV-infected subjects on ART with no significant metabolic disturbances displayed increased sCD14 and sVCAM but not up-regulation of proinflammatory pathways. Larger studies are warranted to assess the impact of a strict metabolic control on cardiovascular risk and to define specific cardiovascular disease preventive strategies in this population.

Subclinical atherosclerosis and markers of immune activation in HIV-infected children and adolescents: the CaroVIH Study.

BACKGROUND: HIV-infected adults display increased cardiovascular disease, probably driven by inflammation and immune activation. These relationships have not been addressed in vertically HIV-infected children and adolescents, a population at very high risk for long-term non-AIDS complications. METHODS: Carotid intima media thickness (IMT) was measured in a cohort of HIV-infected children and adolescents and healthy controls. C-reactive protein and markers of immune activation (CD38⁺HLA-DR⁺) and immune senescence (CD28⁻CD57⁺) were determined. RESULTS: One hundred fifty HIV-infected patients and 150 controls were included, 64.8% female. IMT was thicker in HIV-infected patients (0.434 mm ± 0.025 vs. 0.424 mm ± 0.018, P < 0.001). After adjustment by age, sex, body mass index, and smoking status, HIV infection was independently associated with thicker IMT (odds ratio, 2.28; 95% confidence interval: 1.25 to 4.13; P = 0.007). Among HIV-related variables, a low CD4 nadir was related to an increased IMT. Although HIV-infected subjects presented higher frequencies of activated CD4⁺ and CD8⁺ T cells (P = 0.002 and P = 0.087, respectively), no relation was found between IMT and inflammation, immune activation, or senescence. CONCLUSIONS: Structural changes of the vasculature present early in vertically HIV-infected subjects as well as immune activation and senescence. These patients should be carefully monitored for the prompt detection and early treatment of cardiovascular disease.

Determinants of highly active antiretroviral therapy duration in HIV-1-infected children and adolescents in Madrid, Spain, from 1996 to 2012.

OBJECTIVES: To investigate the duration of sequential HAART regimens and predictors of first-line regimen discontinuation among HIV-1 vertically infected children and adolescents. DESIGN: Multicentre survey of antiretroviral-naïve patients enrolled in the HIV-Paediatric Cohor,t CoRISpeS-Madrid Cohort, Spain. METHODS: Patients with a follow-up of ≥ 1 month spent on HAART, with available baseline CD4 count and HIV-viral load (VL) were included. Time spent on sequential HAART regimens was estimated and multivariable regression was used to identify predictors of time to first-line regimen discontinuation. RESULTS: 104 patients were followed for a median 8 years after starting HAART among 1996-2012; baseline %CD4 was 21.5 (12.3-34.0)and viral load was 5.1 (4.6-5.6) log10 copies/mL. Patients received a mean of 1.9 regimens. Median time on first-line HAART (n = 104) was 64.5 months; second HAART (n = 56) 69.8 months; and third HAART (n = 21) 66.5 months. Eleven (11%) patients were lost to follow-up while on first-line HAART and 54% discontinued (cumulative incidence of 16% and 38% by 1 and 3-year, respectively). The main predictor of first-line regimen discontinuation was suboptimal adherence to antiretrovirals (AHR: 2.60; 95% CI: 1.44-4.70). CONCLUSIONS: Adherence to therapy was the main determinant of the duration of the first-line HAART regimen in children. It is important to identify patients at high risk for non-adherence, such as very young children and adolescents, in provide special care and support to those patients.

The CD4/CD8 ratio as a marker T-cell activation, senescence and activation/exhaustion in treated HIV-infected children and young adults.

We explored the associations of the CD4/CD8 ratio with markers of immunoactivation, immunosenescence and T-cell subsets, in 37 vertically HIV-infected children and adolescents. CD4/CD8 ratio inversion was associated with higher frequencies of activated, senescent and activated/exhausted CD4+ and CD8+ T-cells, and a skewed T-cell phenotype from naive toward effector memory which persisted after the multivariate analysis. Thus, the CD4/CD8 ratio may identify patients with higher immunoactivation despite ART.

Oseltamivir treatment for influenza in hospitalized children without underlying diseases.

AIM: To determine whether the treatment with oseltamivir improves the outcome of children with confirmed influenza infection and no other underlying disease. METHODS: Multicentric, retrospective study performed in 10 hospitals of Madrid between September 2010 and June 2012. All children admitted to the hospitals with confirmed influenza infections were eligible. Children with risk factors for serious disease and nosocomial influenza infections were excluded. Asthma was not considered an exclusion factor. The study compared patients treated and untreated with oseltamivir. Fever duration, oxygen support, antibiotics administration, length of hospital stay, intensive care admission and bacterial complications were analyzed. To compare variables, χ(2) test, Fisher exact test, ANOVA or Mann-Whitney U test were used. RESULTS: Two hundred eighty-seven children were included and 93 of them were treated with oseltamivir (32%). There were no significant differences between treated and untreated patients in days of fever after admission (1.7 ± 2; 2.1 ± 2.9, P > 0.05), length of stay (5.2 ± 3.6; 5.5 ± 3.4, P > 0.05), days of hypoxia (1.6 ± 2.3; 2.1 ± 2.9, P > 0.05), diagnosis of bacterial pneumonia (10%; 17%, P > 0.05), intensive care admission (6.5%; 1.5%,P > 0.05) or antibiotic prescription (44%; 51%, P > 0.05). There were no differences when the population was stratified by age (below or over 1 year) or by the presence or absence of asthma. CONCLUSIONS: There were no proven benefits of treatment with oseltamivir in hospitalized pediatric patients without the underlying diseases or risk factors for developing a serious illness, including those with asthma.

Implementation of occult hepatitis screening in the Spanish cohort of HIV-infected pediatric patients.

Regular screening methods may miss the diagnosis of occult hepatitis B infection and seronegative hepatitis C virus infection in immunocompromised patients. A cross-sectional study within a Spanish cohort of HIV-infected children yielded 6 of 254 (2.4%) possible occult hepatitis B infection cases and 2 of 254 (0.8%) seronegative hepatitis C virus-infected patients. Implementation of occult hepatitis screening in the routine care of these children may be warranted.

Tuberculosis in pediatric solid organ and hematopoietic stem cell transplant recipients.

The burden of tuberculosis after pediatric solid organ transplant or hematopoietic stem cell transplantation has not been well characterized. We report 7 pediatric cases with disseminated (4/7) or pulmonary (3/7) tuberculosis after solid organ transplant (n=6) or hematopoietic stem cell transplantation (n=1) during 26 years. The outcome was favorable in 6 patients. Isoniazid-induced hepatitis and rifampin interactions were common.

Low rates of mother-to-child transmission of HIV-1 and risk factors for infection in Spain: 2000-2007.

BACKGROUND: The objective of the study was to describe temporal patterns in the management of HIV-1 infected women and their newborns and the changes over time in the mother-to-child transmission (MTCT) rates and risk factors. METHODS: A multicenter prospective observational study was performed in Madrid, Spain, from 2000 to 2007. Cohort period 1 (CP1) included births in 2000-2003 and cohort period 2 (CP2) included births in 2004-2007. RESULTS: Of the 803 HIV-infected women and their infants, 427 were in the CP1 and 376 in CP2. Almost all CP2 women received highly active antiretroviral therapy. More women in CP2 received antiretroviral treatment for ≥16 weeks during pregnancy (72.0% in CP1 vs. 84.8% in CP2; P < 0.001). Overall, no differences in trends in mode of delivery were observed. The proportion of women with vaginal deliveries who had undetectable viral loads increased from 31.1% in CP1 to 42.7% in CP2 (P = 0.02). Thirteen children (1.6%, 95% confidence interval: 0.68-2.55) were HIV-1 infected by MTCT. No changes in the rates of infection were observed over time. All the cases of MTCT occurred when antiretroviral treatment was not given or was given for <16 weeks during pregnancy. CONCLUSIONS: Low MTCT rates were observed over time. Lack of timely provision of antiretroviral drugs was the main limitation to develop all preventive interventions available nowadays. Nonsustained control of viral load could be associated with residual transmission.