Casa Garrahan (CG) accommodates children with complex conditions referred nationwide; these child... more Casa Garrahan (CG) accommodates children with complex conditions referred nationwide; these children are seen in children's hospitals located in the Autonomous City of Buenos Aires. Varicella is a highly-contagious disease, with attack rates of up to 90% among susceptible individuals. In closed communities, the implementation of outbreak control measures is critical. To describe the characteristics of children exposed to varicella at CG, the implemented prophylaxis measures and their effectiveness. Prospective, cohort study. Children exposed to varicella at CG between2008 and 2013, their demographic and clinical characteristics, immunization and/or history of varicella, prophylaxis measures, and secondary attack rate were assessed. N: 107. Fifty-three percent (n: 57) were girls. Their median age was 84 months old [interquartile range (IQR): 24-144]. Ninety-five percent (n: 102) had an underlying disease [hemato-oncological disease: 39% (n: 42); neurological disease: 18% (n: 19);...
The literature on the involvement of mannose-binding lectin (MBL) in human immunodeficiency virus... more The literature on the involvement of mannose-binding lectin (MBL) in human immunodeficiency virus (HIV) transmission and acquired immunodeficiency syndrome (AIDS) is conflicting. Polymorphisms in the MBL2 gene reduce the level of protein and alter its structure. Thus, we investigated whether MBL2 alleles and plasma concentrations of MBL are associated with perinatal HIV transmission and disease progression. Frequencies of MBL2 allelic variants (B, C, D, and X) were estimated among 345 HIV-exposed children and 147 blood donors. AIDS-free time was evaluated for different MBL2 genotypes and MBL plasma levels. The median duration of follow-up was 96.5 months. In the Argentinean population, gene frequencies of MBL2 variants were 18%, 15%, and 3% for the X, B, and D alleles, respectively, with no identified C allele. The haplotype XA/XA was associated with an 8-fold risk of acquiring HIV-1 (P= .054; odds ratio [OR], 8.11 [95% confidence interval {CI}, 0.96-67.86]) and almost a 3-fold risk of progression to pediatric AIDS (P= .026; OR, 2.81 [95% CI, 1.14-7.47]). We also found an independent positive correlation between the rate of AIDS progression and MBL plasma concentration (P= .008; OR, 1.28 [95% CI, 1.07-1.55]). Our results demonstrate that homozygosity for the MBL2 promoter genotype XA/XA is an important genetic determinant of HIV-1 acquisition through vertical transmission and the pathogenesis of pediatric HIV/AIDS, via a mechanism that remains to be established.
The APOBEC3G protein is a restriction factor that can inhibit the replication of HIV-1. The virus... more The APOBEC3G protein is a restriction factor that can inhibit the replication of HIV-1. The virus has the capacity to counteract this antiviral activity through the expression of the Vif accessory protein, which recruits a CUL5-based ubiquitin ligase complex that determines APOBEC3G proteasomal degradation. In this work we evaluated in a large pediatric cohort (i) whether single nucleotide polymorphisms of
Background:HIV-1 infection results in severe immunodeficiency when T-cell loss cannot be compensa... more Background:HIV-1 infection results in severe immunodeficiency when T-cell loss cannot be compensated. IL-7 is one of the main cytokines involved in the maintenance of T-cell homeostasis. However, IL-7 can also enhance HIV-1 replication in vivo and lead to an accelerated progression of AIDS.
ABSTRACT The explosive outbreak of pandemic influenza A (H1N1) in Argentina lasted about six week... more ABSTRACT The explosive outbreak of pandemic influenza A (H1N1) in Argentina lasted about six weeks, from mid May to late June, with widespread transmission across the country. Influenza virus represented 82.13% of the cases reporting respiratory virus. Consultations for influenza-like illness in general practices and emergency departments peaked at 309 consultations for every 10,000 inhabitants. Children and young adults were the age groups most affected. From 7 May to 31 October, 2009, 10,248 confirmed cases, 12,471 hospitalizations for severe respiratory disease, and 600 deaths were reported to the Ministry of Health. The most affected group was children under 5 years of age (hospitalization rate 72.99/100,000), followed by the 45–54 year age group. In this latter group, the most frequent preexisting conditions were cardiovascular, respiratory, and metabolic diseases. As in other countries, obesity and pregnancy were risk factors for increased morbidity. The experience of this first pandemic wave has taught us that coordinated work, community education, early treatment with antiviral drugs, and vaccine administration during the next season for high-risk groups are likely to be fundamental tools against the next pandemic wave.
Inadequate antibiotic use is associated with an increased emergence of resistant microorganisms, ... more Inadequate antibiotic use is associated with an increased emergence of resistant microorganisms, higher morbidity and mortality rates, and an impact on public health. To assess the effectiveness of a program aimed at improving the use of antimicrobials in patients hospitalized at Hospital Garrahan. Prospective, longitudinal, before and after study with no control group. From November 1st, 2010 to June 30th, 2011. Patients receiving parenteral antibiotics were included. Newborn infants, burned patients and those receiving prophylactic antibiotics were excluded. The periods before and after implementing discussion and monitoring workshops for antibiotic prescription and distributing treatment guidelines were compared. An univariate analysis and a multiple logistic regression study were performed (STATA 8.0). In the pre-intervention period,376 patients were included; of them, 35.6% had received inadequate treatment. The multiple regression analysis showed that the endpoints for inadequ...
Proceedings of the National Academy of Sciences of the United States of America, Jan 15, 2002
Studies in humans and in experimental models of HIV-1 infection indicate an important role for mo... more Studies in humans and in experimental models of HIV-1 infection indicate an important role for monocyte chemoattractant protein-1 (MCP-1; also known as CC chemokine ligand 2), a potent chemoattractant and activator of mononuclear phagocytes (MP) in the pathogenesis of HIV-associated dementia (HAD). We determined the influence of genetic variation in MCP-1 on HIV-1 pathogenesis in large cohorts of HIV-1-infected adults and children. In adults, homozygosity for the MCP-1 -2578G allele was associated with a 50% reduction in the risk of acquiring HIV-1. However, once HIV-1 infection was established, this same MCP-1 genotype was associated with accelerated disease progression and a 4.5-fold increased risk of HAD. We examined the molecular and cellular basis for these genotype-phenotype associations and found that the mutant MCP-1 -2578G allele conferred greater transcriptional activity via differential DNA-protein interactions, enhanced protein production in vitro, increased serum MCP-1 ...
ABSTRACT The explosive outbreak of pandemic influenza A (H1N1) in Argentina lasted about six week... more ABSTRACT The explosive outbreak of pandemic influenza A (H1N1) in Argentina lasted about six weeks, from mid May to late June, with widespread transmission across the country. Influenza virus represented 82.13% of the cases reporting respiratory virus. Consultations for influenza-like illness in general practices and emergency departments peaked at 309 consultations for every 10,000 inhabitants. Children and young adults were the age groups most affected. From 7 May to 31 October, 2009, 10,248 confirmed cases, 12,471 hospitalizations for severe respiratory disease, and 600 deaths were reported to the Ministry of Health. The most affected group was children under 5 years of age (hospitalization rate 72.99/100,000), followed by the 45–54 year age group. In this latter group, the most frequent preexisting conditions were cardiovascular, respiratory, and metabolic diseases. As in other countries, obesity and pregnancy were risk factors for increased morbidity. The experience of this first pandemic wave has taught us that coordinated work, community education, early treatment with antiviral drugs, and vaccine administration during the next season for high-risk groups are likely to be fundamental tools against the next pandemic wave.
The aim of this study was to determine the causes of fever of unknown origin, to evaluate new dia... more The aim of this study was to determine the causes of fever of unknown origin, to evaluate new diagnostic tests and to elucidate risk factors for chronic or life-threatening disorders. The medical records of 113 children who had undiagnosed fever for at least 3 weeks were reviewed. Infection (N = 41) was the most frequent cause of fever of unknown origin. Respiratory tract infections were the most common causes in infants and endocarditis and tuberculosis were more frequent in older children. Neoplastic disorders (N = 11) occurred in children older than one year. Juvenile rheumatoid arthritis (N = 9) was the most common collagen-vascular disorder (N = 15). Miscellaneous disorders and factitious fever occurred in 21 and 4 cases, respectively. Twenty-two patients remained undiagnosed. History and physical examination led to a final diagnosis in 81% of cases. Abdominal ultrasonography was performed in 71 patients (61%) and was helpful for diagnosis in 15%. Children with life-threatening or chronic disorders (N = 58) were older than those with self-limiting conditions (N = 55; P = 0.017). Cardiovascular and articular signs and symptoms were more frequent in the former group (P = 0.01).
The aim of this work is to: (1) assess therapeutic drug monitoring of indinavir (IDV) during clin... more The aim of this work is to: (1) assess therapeutic drug monitoring of indinavir (IDV) during clinical routine practice in HIV-infected children, whose antiretroviral treatment includes IDV boosted with ritonavir (RTV), and (2) describe a possible relationship between IDV pharmacokinetics and MDR1 genotypes. In 21 ambulatory pediatric patients receiving IDV plus RTV, IDV plasma levels and MDR1 genotypes on exon 26 (C3435T) were determined. Nine of the 21 patients initially receiving 250 mg/m(2) IDV yielded trough levels below 0.10 microg/ml (median: 0.21, range: 0.04-1.31 microg/ml). When the dosage was increased to 400 mg/m(2) IDV plus 100 mg/m(2) RTV b.i.d., all, except 1 patient, achieved levels above 0.10 microg/ml. Pharmacokinetic analysis showed higher volume of distribution median values related to the C/C genotype in comparison with C/T or T/T genotypes for exon 26 (4.57 vs. 1.20 and 1.50 l/kg, respectively; p = 0.002). Although a higher median value of clearance was observed with the C/C genotype, the difference was not statistically significant (1.43 vs. 0.27 and 0.42 l/h, respectively; p = 0.052). These results may be explained by a reduced absorption of the drug, related with lower plasma IDV levels in patients carrying the C/C genotype in exon 26.
Previously we demonstrated that monocyte phagolysosomal fusion is impaired in chronic HIV infecti... more Previously we demonstrated that monocyte phagolysosomal fusion is impaired in chronic HIV infection in adult patients. We studied the phagolysosomal fusion of peripheral blood monocytes from 45 children vertically infected with HIV, 38 noninfected infants born to HIV-positive mothers and 14 children born to HIV-seronegative women, by a cytomorphologic method in which acridine orange is used as a fusion marker. The mean percentages of phagolysosomal fusion +/-SD were 42 +/- 16.1 for HIV-positive children, 55.3 +/- 15.5 for HIV-negative infants born to HIV-infected mothers and 58.2 +/- 12.7 for normal controls. Monocyte phagolysosomal fusion of HIV-infected children was significantly decreased in comparison to noninfected and normal infants (P < 0.001), while there was no difference between the two latter groups. Phagolysosomal fusion impairment in HIV-infected infants inversely correlated with age (r = -0.4527; P < 0.002) and directly correlated with CD4+ T cell counts (r = 0.393; P = 0.03). Moreover, phagolysosomal fusion strongly correlated with clinical manifestations; this function was significantly impaired in moderately and severely symptomatic HIV-infected children with respect to those who remained asymptomatic or mildly symptomatic (P < 0.05). Our results suggest that monocyte function in HIV-infected children progressively deteriorates, closely related to the severity of the clinical symptoms.
Although host defense against human immunodeficiency virus 1 (HIV-1) relies mainly on cell-mediat... more Although host defense against human immunodeficiency virus 1 (HIV-1) relies mainly on cell-mediated immunity (CMI), the determinants of CMI in humans are poorly understood. Here we demonstrate that variations in the genes encoding the chemokine CCL3L1 and HIV coreceptor CCR5 influence CMI in both healthy and HIV-infected individuals. CCL3L1-CCR5 genotypes associated with altered CMI in healthy subjects were similar to those that influence the risk of HIV transmission, viral burden and disease progression. However, CCL3L1-CCR5 genotypes also modify HIV clinical course independently of their effects on viral load and CMI. These results identify CCL3L1 and CCR5 as major determinants of CMI and demonstrate that these host factors influence HIV pathogenesis through their effects on both CMI and other viral entry-independent mechanisms.
If CC chemokine receptor 5 (CCR5)-dependent mechanisms at the time of initial virus exposure are ... more If CC chemokine receptor 5 (CCR5)-dependent mechanisms at the time of initial virus exposure are important determinants of virus entry and disease outcome, then the polymorphisms in CCR5 that influence risk of transmission and disease progression should be similar; this hypothesis was tested in a cohort of 649 Argentinean children exposed perinatally to human immunodeficiency virus type 1 (HIV-1). Two lines of evidence support this hypothesis. First, CCR5 haplotype pairs associated with enhanced risk of transmission were the chief predictors of a faster disease course. Second, some of the haplotype pairs associated with altered rates of transmission and disease progression in children were similar to those that we previously found influenced outcome in European American adults. This concordance suggests that CCR5 haplotypes may serve as genetic rheostats that influence events occurring shortly after initial virus exposure, dictating not only virus entry but, by extension, also the extent of early viral replication.
Enfermedades Infecciosas y Microbiología Clínica, 2004
... El Hospital de Pediatría Juan P. Garrahan de Buenos Aires (Argentina) es un importante com-pl... more ... El Hospital de Pediatría Juan P. Garrahan de Buenos Aires (Argentina) es un importante com-plejo hospitalario, que cuenta con ... Se consideró endocarditis infec-ciosa en válvula protésica cuando la infección se producía sobre material exógeno colocado dentro del corazón (p ...
A post hoc analysis of 654 children with bacterial meningitis showed that the level of consciousn... more A post hoc analysis of 654 children with bacterial meningitis showed that the level of consciousness is the most important predictor of death and/or neurological sequelae, more than is etiology per se. This finding emphasizes the need of including a measurement of the presenting status in all studies examining treatment efficacy.
Casa Garrahan (CG) accommodates children with complex conditions referred nationwide; these child... more Casa Garrahan (CG) accommodates children with complex conditions referred nationwide; these children are seen in children's hospitals located in the Autonomous City of Buenos Aires. Varicella is a highly-contagious disease, with attack rates of up to 90% among susceptible individuals. In closed communities, the implementation of outbreak control measures is critical. To describe the characteristics of children exposed to varicella at CG, the implemented prophylaxis measures and their effectiveness. Prospective, cohort study. Children exposed to varicella at CG between2008 and 2013, their demographic and clinical characteristics, immunization and/or history of varicella, prophylaxis measures, and secondary attack rate were assessed. N: 107. Fifty-three percent (n: 57) were girls. Their median age was 84 months old [interquartile range (IQR): 24-144]. Ninety-five percent (n: 102) had an underlying disease [hemato-oncological disease: 39% (n: 42); neurological disease: 18% (n: 19);...
The literature on the involvement of mannose-binding lectin (MBL) in human immunodeficiency virus... more The literature on the involvement of mannose-binding lectin (MBL) in human immunodeficiency virus (HIV) transmission and acquired immunodeficiency syndrome (AIDS) is conflicting. Polymorphisms in the MBL2 gene reduce the level of protein and alter its structure. Thus, we investigated whether MBL2 alleles and plasma concentrations of MBL are associated with perinatal HIV transmission and disease progression. Frequencies of MBL2 allelic variants (B, C, D, and X) were estimated among 345 HIV-exposed children and 147 blood donors. AIDS-free time was evaluated for different MBL2 genotypes and MBL plasma levels. The median duration of follow-up was 96.5 months. In the Argentinean population, gene frequencies of MBL2 variants were 18%, 15%, and 3% for the X, B, and D alleles, respectively, with no identified C allele. The haplotype XA/XA was associated with an 8-fold risk of acquiring HIV-1 (P= .054; odds ratio [OR], 8.11 [95% confidence interval {CI}, 0.96-67.86]) and almost a 3-fold risk of progression to pediatric AIDS (P= .026; OR, 2.81 [95% CI, 1.14-7.47]). We also found an independent positive correlation between the rate of AIDS progression and MBL plasma concentration (P= .008; OR, 1.28 [95% CI, 1.07-1.55]). Our results demonstrate that homozygosity for the MBL2 promoter genotype XA/XA is an important genetic determinant of HIV-1 acquisition through vertical transmission and the pathogenesis of pediatric HIV/AIDS, via a mechanism that remains to be established.
The APOBEC3G protein is a restriction factor that can inhibit the replication of HIV-1. The virus... more The APOBEC3G protein is a restriction factor that can inhibit the replication of HIV-1. The virus has the capacity to counteract this antiviral activity through the expression of the Vif accessory protein, which recruits a CUL5-based ubiquitin ligase complex that determines APOBEC3G proteasomal degradation. In this work we evaluated in a large pediatric cohort (i) whether single nucleotide polymorphisms of
Background:HIV-1 infection results in severe immunodeficiency when T-cell loss cannot be compensa... more Background:HIV-1 infection results in severe immunodeficiency when T-cell loss cannot be compensated. IL-7 is one of the main cytokines involved in the maintenance of T-cell homeostasis. However, IL-7 can also enhance HIV-1 replication in vivo and lead to an accelerated progression of AIDS.
ABSTRACT The explosive outbreak of pandemic influenza A (H1N1) in Argentina lasted about six week... more ABSTRACT The explosive outbreak of pandemic influenza A (H1N1) in Argentina lasted about six weeks, from mid May to late June, with widespread transmission across the country. Influenza virus represented 82.13% of the cases reporting respiratory virus. Consultations for influenza-like illness in general practices and emergency departments peaked at 309 consultations for every 10,000 inhabitants. Children and young adults were the age groups most affected. From 7 May to 31 October, 2009, 10,248 confirmed cases, 12,471 hospitalizations for severe respiratory disease, and 600 deaths were reported to the Ministry of Health. The most affected group was children under 5 years of age (hospitalization rate 72.99/100,000), followed by the 45–54 year age group. In this latter group, the most frequent preexisting conditions were cardiovascular, respiratory, and metabolic diseases. As in other countries, obesity and pregnancy were risk factors for increased morbidity. The experience of this first pandemic wave has taught us that coordinated work, community education, early treatment with antiviral drugs, and vaccine administration during the next season for high-risk groups are likely to be fundamental tools against the next pandemic wave.
Inadequate antibiotic use is associated with an increased emergence of resistant microorganisms, ... more Inadequate antibiotic use is associated with an increased emergence of resistant microorganisms, higher morbidity and mortality rates, and an impact on public health. To assess the effectiveness of a program aimed at improving the use of antimicrobials in patients hospitalized at Hospital Garrahan. Prospective, longitudinal, before and after study with no control group. From November 1st, 2010 to June 30th, 2011. Patients receiving parenteral antibiotics were included. Newborn infants, burned patients and those receiving prophylactic antibiotics were excluded. The periods before and after implementing discussion and monitoring workshops for antibiotic prescription and distributing treatment guidelines were compared. An univariate analysis and a multiple logistic regression study were performed (STATA 8.0). In the pre-intervention period,376 patients were included; of them, 35.6% had received inadequate treatment. The multiple regression analysis showed that the endpoints for inadequ...
Proceedings of the National Academy of Sciences of the United States of America, Jan 15, 2002
Studies in humans and in experimental models of HIV-1 infection indicate an important role for mo... more Studies in humans and in experimental models of HIV-1 infection indicate an important role for monocyte chemoattractant protein-1 (MCP-1; also known as CC chemokine ligand 2), a potent chemoattractant and activator of mononuclear phagocytes (MP) in the pathogenesis of HIV-associated dementia (HAD). We determined the influence of genetic variation in MCP-1 on HIV-1 pathogenesis in large cohorts of HIV-1-infected adults and children. In adults, homozygosity for the MCP-1 -2578G allele was associated with a 50% reduction in the risk of acquiring HIV-1. However, once HIV-1 infection was established, this same MCP-1 genotype was associated with accelerated disease progression and a 4.5-fold increased risk of HAD. We examined the molecular and cellular basis for these genotype-phenotype associations and found that the mutant MCP-1 -2578G allele conferred greater transcriptional activity via differential DNA-protein interactions, enhanced protein production in vitro, increased serum MCP-1 ...
ABSTRACT The explosive outbreak of pandemic influenza A (H1N1) in Argentina lasted about six week... more ABSTRACT The explosive outbreak of pandemic influenza A (H1N1) in Argentina lasted about six weeks, from mid May to late June, with widespread transmission across the country. Influenza virus represented 82.13% of the cases reporting respiratory virus. Consultations for influenza-like illness in general practices and emergency departments peaked at 309 consultations for every 10,000 inhabitants. Children and young adults were the age groups most affected. From 7 May to 31 October, 2009, 10,248 confirmed cases, 12,471 hospitalizations for severe respiratory disease, and 600 deaths were reported to the Ministry of Health. The most affected group was children under 5 years of age (hospitalization rate 72.99/100,000), followed by the 45–54 year age group. In this latter group, the most frequent preexisting conditions were cardiovascular, respiratory, and metabolic diseases. As in other countries, obesity and pregnancy were risk factors for increased morbidity. The experience of this first pandemic wave has taught us that coordinated work, community education, early treatment with antiviral drugs, and vaccine administration during the next season for high-risk groups are likely to be fundamental tools against the next pandemic wave.
The aim of this study was to determine the causes of fever of unknown origin, to evaluate new dia... more The aim of this study was to determine the causes of fever of unknown origin, to evaluate new diagnostic tests and to elucidate risk factors for chronic or life-threatening disorders. The medical records of 113 children who had undiagnosed fever for at least 3 weeks were reviewed. Infection (N = 41) was the most frequent cause of fever of unknown origin. Respiratory tract infections were the most common causes in infants and endocarditis and tuberculosis were more frequent in older children. Neoplastic disorders (N = 11) occurred in children older than one year. Juvenile rheumatoid arthritis (N = 9) was the most common collagen-vascular disorder (N = 15). Miscellaneous disorders and factitious fever occurred in 21 and 4 cases, respectively. Twenty-two patients remained undiagnosed. History and physical examination led to a final diagnosis in 81% of cases. Abdominal ultrasonography was performed in 71 patients (61%) and was helpful for diagnosis in 15%. Children with life-threatening or chronic disorders (N = 58) were older than those with self-limiting conditions (N = 55; P = 0.017). Cardiovascular and articular signs and symptoms were more frequent in the former group (P = 0.01).
The aim of this work is to: (1) assess therapeutic drug monitoring of indinavir (IDV) during clin... more The aim of this work is to: (1) assess therapeutic drug monitoring of indinavir (IDV) during clinical routine practice in HIV-infected children, whose antiretroviral treatment includes IDV boosted with ritonavir (RTV), and (2) describe a possible relationship between IDV pharmacokinetics and MDR1 genotypes. In 21 ambulatory pediatric patients receiving IDV plus RTV, IDV plasma levels and MDR1 genotypes on exon 26 (C3435T) were determined. Nine of the 21 patients initially receiving 250 mg/m(2) IDV yielded trough levels below 0.10 microg/ml (median: 0.21, range: 0.04-1.31 microg/ml). When the dosage was increased to 400 mg/m(2) IDV plus 100 mg/m(2) RTV b.i.d., all, except 1 patient, achieved levels above 0.10 microg/ml. Pharmacokinetic analysis showed higher volume of distribution median values related to the C/C genotype in comparison with C/T or T/T genotypes for exon 26 (4.57 vs. 1.20 and 1.50 l/kg, respectively; p = 0.002). Although a higher median value of clearance was observed with the C/C genotype, the difference was not statistically significant (1.43 vs. 0.27 and 0.42 l/h, respectively; p = 0.052). These results may be explained by a reduced absorption of the drug, related with lower plasma IDV levels in patients carrying the C/C genotype in exon 26.
Previously we demonstrated that monocyte phagolysosomal fusion is impaired in chronic HIV infecti... more Previously we demonstrated that monocyte phagolysosomal fusion is impaired in chronic HIV infection in adult patients. We studied the phagolysosomal fusion of peripheral blood monocytes from 45 children vertically infected with HIV, 38 noninfected infants born to HIV-positive mothers and 14 children born to HIV-seronegative women, by a cytomorphologic method in which acridine orange is used as a fusion marker. The mean percentages of phagolysosomal fusion +/-SD were 42 +/- 16.1 for HIV-positive children, 55.3 +/- 15.5 for HIV-negative infants born to HIV-infected mothers and 58.2 +/- 12.7 for normal controls. Monocyte phagolysosomal fusion of HIV-infected children was significantly decreased in comparison to noninfected and normal infants (P < 0.001), while there was no difference between the two latter groups. Phagolysosomal fusion impairment in HIV-infected infants inversely correlated with age (r = -0.4527; P < 0.002) and directly correlated with CD4+ T cell counts (r = 0.393; P = 0.03). Moreover, phagolysosomal fusion strongly correlated with clinical manifestations; this function was significantly impaired in moderately and severely symptomatic HIV-infected children with respect to those who remained asymptomatic or mildly symptomatic (P < 0.05). Our results suggest that monocyte function in HIV-infected children progressively deteriorates, closely related to the severity of the clinical symptoms.
Although host defense against human immunodeficiency virus 1 (HIV-1) relies mainly on cell-mediat... more Although host defense against human immunodeficiency virus 1 (HIV-1) relies mainly on cell-mediated immunity (CMI), the determinants of CMI in humans are poorly understood. Here we demonstrate that variations in the genes encoding the chemokine CCL3L1 and HIV coreceptor CCR5 influence CMI in both healthy and HIV-infected individuals. CCL3L1-CCR5 genotypes associated with altered CMI in healthy subjects were similar to those that influence the risk of HIV transmission, viral burden and disease progression. However, CCL3L1-CCR5 genotypes also modify HIV clinical course independently of their effects on viral load and CMI. These results identify CCL3L1 and CCR5 as major determinants of CMI and demonstrate that these host factors influence HIV pathogenesis through their effects on both CMI and other viral entry-independent mechanisms.
If CC chemokine receptor 5 (CCR5)-dependent mechanisms at the time of initial virus exposure are ... more If CC chemokine receptor 5 (CCR5)-dependent mechanisms at the time of initial virus exposure are important determinants of virus entry and disease outcome, then the polymorphisms in CCR5 that influence risk of transmission and disease progression should be similar; this hypothesis was tested in a cohort of 649 Argentinean children exposed perinatally to human immunodeficiency virus type 1 (HIV-1). Two lines of evidence support this hypothesis. First, CCR5 haplotype pairs associated with enhanced risk of transmission were the chief predictors of a faster disease course. Second, some of the haplotype pairs associated with altered rates of transmission and disease progression in children were similar to those that we previously found influenced outcome in European American adults. This concordance suggests that CCR5 haplotypes may serve as genetic rheostats that influence events occurring shortly after initial virus exposure, dictating not only virus entry but, by extension, also the extent of early viral replication.
Enfermedades Infecciosas y Microbiología Clínica, 2004
... El Hospital de Pediatría Juan P. Garrahan de Buenos Aires (Argentina) es un importante com-pl... more ... El Hospital de Pediatría Juan P. Garrahan de Buenos Aires (Argentina) es un importante com-plejo hospitalario, que cuenta con ... Se consideró endocarditis infec-ciosa en válvula protésica cuando la infección se producía sobre material exógeno colocado dentro del corazón (p ...
A post hoc analysis of 654 children with bacterial meningitis showed that the level of consciousn... more A post hoc analysis of 654 children with bacterial meningitis showed that the level of consciousness is the most important predictor of death and/or neurological sequelae, more than is etiology per se. This finding emphasizes the need of including a measurement of the presenting status in all studies examining treatment efficacy.
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