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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

High drug resistance prevalence among vertically HIV-infected patients transferred from pediatric care to adult units in Spain.

BACKGROUND: Antiretroviral treatment (ART) has contributed to increased life expectancy of HIV-1 infected children. In developed countries, an increasing number of children reaching adulthood are transferred to adult units. The objectives were to describe the demographic and clinical features, ART history, antiviral drug resistance and drug susceptibility in HIV-1 perinatally infected adolescents transferred to adult care units in Spain from the Madrid Cohort of HIV-1 infected children. METHODS: Clinical, virological and immunological features of HIV-1 vertically infected patients in the Madrid Cohort of HIV-infected children were analyzed at the time of transfer. Pol sequences from each patient were recovered before transfer. Resistance mutations according to the InternationaI AIDS Society 2011 list were identified and interpreted using the Stanford algorithm. Results were compared to the non-transferred HIV-1 infected pediatric cohort from Madrid. RESULTS: One hundred twelve infected patients were transferred to adult units between 1997 and 2011. They were mainly perinatally infected (93.7%), with a mean nadir CD4+-T-cells count of 10% and presented moderate or severe clinical symptoms (75%). By the time of transfer, the mean age was 18.9 years, the mean CD4+T-cells count was 627.5 cells/ml, 64.2% presented more than 350 CD4+T-cells/ml and 47.3% had ≤ 200 RNA-copies/ml. Most (97.3%) were ART experienced receiving Highly Active ART (HAART) (84.8%). Resistance prevalence among pretreated was 50.9%, 76.9% and 36.5% for Protease Inhibitors (PI), Nucleoside Reverse Transcriptase Inhibitors (NRTI) and Non-NRTI (NNRTI), respectively. Resistance mutations were significantly higher among transferred patients compared to non-transferred for the PI+NRTI combination (19% vs. 8.4%). Triple resistance was similar to non-transferred pediatric patients (17.3% vs. 17.6%). CONCLUSION: Despite a good immunological and virological control before transfer, we found high levels of resistance to PI, NRTI and triple drug resistance in HIV-1 infected adolescents transferred to adult units.

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.

Association between lipodystrophy and leptin in human immunodeficiency virus-1-infected children receiving lopinavir/ritonavir-based therapy.

Highly active antiretroviral therapy might lead to the development of dyslipidemia and lipodystrophy (LD) syndrome. We carried out a multicenter prospective study of 22 human immunodeficiency virus (HIV)-1-infected children treated during 48 months with lopinavir/ritonavir-based highly active antiretroviral therapy to evaluate the trend of serum lipids and adipokines. Increase in plasma leptin levels and leptin/adiponectin ratio was associated with LD. These adipokines may be surrogate markers of LD.

Comparison of levels of antiretroviral drugs with efficacy in children with HIV infection.

OBJECTIVE: To determine the prevalence of low and high antiretroviral (ARV) plasma levels and to analyze correlation between ARV concentrations and the appearance of therapeutic failure and toxicity. METHODS: The authors present here a study evaluating antiretroviral plasma concentrations in HIV infected children on nonnucleoside reverse transcriptase inhibitors and protease inhibitors based therapy. The authors carried out a multicentre, cross-sectional study, including HIV-infected children from five large Hospitals in Madrid, Spain. Clinical, haematological, biochemical and immuno-virological parameters were assessed. Antiretroviral plasma trough levels were performed using a validated high performance liquid chromatography method. RESULTS: Between April 2006 and April 2008, 129 children were enrolled in the present study, with median treatment duration of 39.2 months. 25.5% of the non-nucleoside reverse transcriptase inhibitors levels were low and 17.6%, high. 27.9% percent of the protease inhibitors levels were low and 12.5%, high. A correlation was found among adequate or high levels of antiretrovirals and normal CD4 percentage and low viral load. Lopinavir/ritonavir plasma levels were correlated with an increase in lipodystrophy. Patients with Tanner stage 1 presented the lowest ARV plasma levels. Full adherence was reported for all the participants by a questionnaire. CONCLUSION: Many HIV-infected children show ARV plasma levels out of the therapeutic range which demands a child-adjusted approach. However, larger studies are urgently needed in pediatric populations to define optimal reference values.

Impact of immigration on pulmonary tuberculosis in Spanish children: a three-decade review.

BACKGROUND: Tuberculosis causes significant morbidity and mortality worldwide. In the last years, international travel and immigration have led to important changes in the epidemiology of this disease. Drug resistance has emerged as an important threat to tuberculosis control. Data regarding the impact of immigration and the incidence of drug-resistant strains in children are lacking. METHODS: Retrospective review of patients diagnosed with pulmonary tuberculosis at La Paz Children's Hospital in a 30-year period. Data were collected with regard to the clinical, radiologic, microbiologic, and demographic characteristics of patients, and data from the 3 decades of the study were compared using chi test and Fisher exact test. RESULTS: A total of 507 cases of tuberculosis were identified, 414 of which had pulmonary involvement. During the study, there was a significant decrease in tuberculous meningitis: 10.4% in 1978-1987, 5.6% in 1988-1997, and 2.9% in 1998-2007 (P < 0.05). The most frequent reason for a consultation was case contact investigation. The adult source case was identified in 64% of patients. We observed an increase in extrafamilial contacts (8% in 1978-1987 and 18% in 1998-2007, P < 0.01), including 4 cases of immigrant caretakers. Tuberculosis in immigrant children has increased with time: 2% in the period 1978-1987, 6% in 1988-1997, and 46% in 1998-2007 (P < 0.001). The primary resistance rate to isoniazid in our population was 6.5%. CONCLUSIONS: Tuberculosis in our area continues to be a major health problem, especially among foreign-born children. As drug-resistant strains are increasing, initial therapy with 4 drugs is recommended in our population.

[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.