Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0021051 (immunodeficiency)
71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Virtually all pediatric acquired immunodeficiency syndrome (AIDS) cases result from either vertical infection (transmission from mother to child before or at birth) or infection through transfusion with blood products that contain the human immunodeficiency virus (HIV). The risk of passing HIV infection on to an unborn child is about 25-30% if the mother is essentially healthy and higher if the mother is already showing signs of AIDS. Since maternal antibodies can persist in the infant's blood for as long as 15 months after birth, it is difficult to tell whether a positive HIV test result in an infant under this age is valid. The clinical case definition of pediatric AIDS requires the presence of 2 major signs (weight loss or abnormally slow growth, chronic diarrhea for more than 1 months, or prolonged or intermittent fever for more than 1 month) and 2 minor signs (generalized lymph node enlargement, oropharyngeal candidiasis, recurrent infections, generalized dementia, persistent cough for more than 1 month, or confirmed infection with HIV in the mother). However, diagnosis is complicated by the fact that signs and symptoms associated with HIV infection are similar to those of other treatable diseases common among children in developing countries (e.g., malnutrition, tuberculosis, and chronic diarrhea). Mothers are advised to continue breastfeeding, even where HIV indication is indicated, since there is no evidence that nursing is a significant route of infection. In addition, there is no evidence that immunizations given by trained health workers using sterile equipment transmit HIV infection.
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PMID:Children, HIV infection and AIDS. 1228 29

These recommendations update the February 4,2002, guidelines developed by the Public Health Service for the use of zidovudine (ZDV) to reduce the risk for perinatal human immunodeficiency virus type 1 (HIV-1) transmission. This report provides healthcare providers with information for discussion with HIV-1-infected pregnant women to enable such women to make an informed decision regarding the use of antiretroviral drugs during pregnancy and use of elective cesarean delivery to reduce perinatal HIV-1 transmission. Various circumstances that commonly occur in clinical practice are presented, and the factors influencing treatment considerations are highlighted in this report. The Perinatal HIV Guidelines Working Group recognizes that strategies to prevent perinatal transmission and concepts related to management of HIV disease in pregnant women are rapidly evolving and will continually review new data and provide regular updates to the guidelines. The most recent information is available from the HIV/AIDS Treatment Information Service (available at http.//www.hivatis.org). In February 1994, the results of Pediatric AIDS Clinical Trials Group (PACTG) Protocol 076 documented that ZDV chemoprophylaxis could reduce perinatal HIV-1 transmission by nearly 70%. Epidemiologic data have since confirmed the efficacy of ZDV for reduction of perinatal transmission and have extended this efficacy to children of women with advanced disease, low CD4+ T-lymphocyte counts, and prior ZDV therapy. Additionally, substantial advances have been made in the understanding of the pathogenesis of HIV-1 infection and in the treatment and monitoring of persons with HIV-1 disease. These advances have resulted in changes in standard antiretroviral therapy for HIV-1-infected adults. More aggressive combination drug regimens that maximally suppress viral replication are now recommended. Although considerations associated with pregnancy may affect decisions regarding timing and choice of therapy pregnancy is not a reason to defer standard therapy. Use of antiretroviral drugs in pregnancy requires unique considerations, including the possible need to alter dosage as a result of physiologic changes associated with pregnancy the potential for adverse short- or long-term effects on the fetus and newborn, and the effectiveness of the drugs in reducing the risk for perinatal transmission. Data to address many of these considerations are not yet available. Therefore, offering antiretroviral therapy to HIV-1-infected women during pregnancy, whether primarily for HIV-1 infection, for reduction of perinatal transmission, or for both purposes, should be accompanied by a discussion of the known and unknown short- and long-term benefits and risks of such therapy to infected women and their infants. Standard antiretroviral therapy should be discussed with and offered to HIV-1-infected pregnant women. Additionally, to prevent perinatal transmission, ZDV chemoprophylaxis should be incorporated into the antiretroviral regimen.
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PMID:U.S. Public Health Service Task Force recommendations for use of antiretroviral drugs in pregnant HIV-1-infected women for maternal health and interventions to reduce perinatal HIV-1 transmission in the United States. 1248 44

The normal value of the absolute CD4-positive T-lymphocyte count is relatively high in normal infants and declines steadily until 6 years of age, whereas the CD4 percentage of the total lymphocyte count is constant. The immunologic categories according to the 1994 revised pediatric human immunodeficiency virus (HIV) classification, based on CD4-positive percentage of the total lymphocyte count, is classified into three categories: no evidence of suppression (> or =25%), moderate suppression (15-24%), and severe suppression (1-14%). Our objective was to determine the prevalence of mucocutaneous findings in pediatric acquired immunodeficiency syndrome (AIDS) related to the degree of immunosuppression. We prospectively examined 120 children less than 13 years of age who were born to HIV-seropositive women and developed definite HIV infection. The prevalence of mucocutaneous findings in those children who had severe, moderate, and no evidence of immunosuppression were 62%, 43%, and 20%, respectively. The mucocutaneous findings in patients in the moderate and severe suppression groups were significantly more common than in patients without evidence of immunosuppression (p < 0.001). In the moderate immunosuppression group, 11% had two mucocutaneous findings while 21% in the severe immunosuppression group had two or more mucocutaneous findings. The most common mucocutaneous finding was oral candidiasis (33%), which had a mean corresponding CD4 percentage of the total lymphocyte count of 11.3%. Herpes zoster was found in 6% of the patients (mean CD4 percentage of the total lymphocyte count = 13.5%). Chronic herpes simplex virus (HSV) stomatitis was found in 3% of the patients (mean CD4 percentage of the total lymphocyte count = 3%). Mucocutaneous manifestations are common in pediatric AIDS. The majority of these findings have an infectious etiology. The prevalence increases as the CD4-positive percentage of the total lymphocyte count decreases. More than one mucocutaneous finding can be found at the same time in patients with moderate or severe immunosuppression.
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PMID:Mucocutaneous findings in pediatric AIDS related to degree of immunosuppression. 1286 45

Intrapatient variability of drug concentrations over time has not been evaluated as a predictor of drug response but may provide information on the onset and maintenance of response and a patient's adherence to therapy. Our objective was to develop a pharmacologically based measure of intrapatient variability of concentrations and investigate its association with a patient's response to antiretroviral therapy. Efavirenz concentrations were obtained for 50 children enrolled in Pediatric AIDS Clinical Trials Group study 382, a concentration-controlled trial of efavirenz plus nelfinavir and at least one nucleoside reverse transcriptase inhibitor. Efavirenz pharmacokinetic parameters were determined from 24-h concentration-time profiles at weeks 2 and 6 and used to predict trough concentrations obtained during 1 year of therapy. A concentration predictability score, defined as the fraction of measured trough concentrations that fell within a +/-50% range of the predicted concentration, was used to place subjects into high and low concentration predictability groups. Relationships between this score and human immunodeficiency virus RNA levels in plasma were investigated. Eight of 33 children (24%) in the high-predictability group experienced viral rebound, compared with 9 of 17 children (53%) in the low-predictability group (P = 0.042). Children with low predictability scores exhibited a significantly shorter time to their first viral rebounds and were significantly more likely to experience viral rebound; the latter finding persisted after adjustment for baseline viral load and efavirenz exposure at week 6. This novel method for the quantitation of intrapatient concentration variability was independently predictive of virologic rebound. This measure may allow interventions to minimize therapeutic failure and is applicable to other drugs.
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PMID:Intrapatient variability of efavirenz concentrations as a predictor of virologic response to antiretroviral therapy. 1498 92

This study of a subset of women and infants participating in National Institutes of Health Pediatric AIDS Clinical Trials Group protocol 185 evaluated lymphocyte phenotypic markers of immune activation and differentiation to determine their association with the likelihood of human immunodeficiency virus (HIV) transmission from the women to their infants and the potential for early identification and/or prognosis of infection in the infants. Lymphocytes from 215 human immunodeficiency virus type 1 (HIV)-infected women and 192 of their infants were analyzed by flow cytometry with an extended three-color panel of monoclonal antibodies. Women who did not transmit to their infants tended to have higher CD4+ T cells. Most notably, levels of total CD8+ T cells and CD8+ CD38+ cells made significant independent contributions to predicting the risk of mother-to-child transmission. Adjusting for HIV-1 RNA level at entry, a one percentage-point increase in these marker combinations was associated with a nine percent increase in the likelihood of maternal transmission. Total as well as naive CD4+ T cells were significantly higher in uninfected than infected infants. Total CD8+ cells, as well as CD8+ cells positive for HLA-DR+, CD45 RA+ HLA-DR+, and CD28+ HLA-DR+ were elevated in infected infants. Detailed immunophenotyping may be helpful in predicting which pregnant HIV-infected women are at increased risk of transmitting HIV to their infants. Increasing differences in lymphocyte subsets between infected and uninfected infants became apparent as early as six weeks of age. Detailed immunophenotyping may be useful in supporting the diagnosis of HIV infection in infants with perinatal HIV exposure.
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PMID:Association of selected phenotypic markers of lymphocyte activation and differentiation with perinatal human immunodeficiency virus transmission and infant infection. 1587 23

Pediatric AIDS Clinical Trials Group protocol 326 is a study of 2 formulations of recombinant canarypox ALVAC vaccine (vCP205) against human immunodeficiency virus type 1 (HIV-1). HIV-1-exposed infants were randomized to receive 1 of 2 formulations of vCP205 or placebo at birth and 4, 8, and 12 weeks. The vaccines were safe. Lymphoproliferative responses were detected at > or =2 time points in 44%-56% of vaccinees and none of the placebo recipients. A cytotoxic T lymphocyte response on at least 1 occasion was detected in 62.5% of infants in cohort 1 (10(6.08) median tissue culture dose [TCID(50)] vaccine formulation) and 44% of infants in cohort 2 (10(6.33) TCID(50) vaccine formulation). Rare mucosal immunoglobulin A responses and no measurable vaccine-elicited serum antibodies were detected. In children, vCP205 appeared to be safe and immunogenic.
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PMID:Safety and immunogenicity of an HIV-1 recombinant canarypox vaccine in newborns and infants of HIV-1-infected women. 1628 78

This article reviews the experiences of programs designed to provide access to prevention of mother-to-child transmission services with the goal of improving services in resource-constrained settings. The article reports new data from the Elizabeth Glaser Pediatric AIDS Foundation's prevention of mother-to-child transmission program in sub-Saharan Africa, which has provided human immunodeficiency virus testing to more than 1,300,000 pregnant women and antiretroviral prophylaxis to 134,000 human immunodeficiency virus-infected pregnant women and more than 78,000 human immunodeficiency virus-exposed infants. Review of qualitative program data highlights the practical innovations that sites are implementing to improve the uptake of prevention of mother-to-child transmission services. Recommendations discussed include opt-out counseling and testing, rapid human immunodeficiency virus testing in antenatal care, counseling and testing in maternity, and provision of antiretroviral prophylaxis for mother and infant at the time of human immunodeficiency virus testing. Successful programmatic innovations need to be disseminated widely as more aggressive prevention strategies must be implemented to increase access to more than 10% of pregnant women worldwide.
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PMID:Site-specific interventions to improve prevention of mother-to-child transmission of human immunodeficiency virus programs in less developed settings. 1782 41

This study aimed to determine lamivudine disposition in infants and to construct an appropriate dose adjustment for age, given the widespread use of lamivudine for both the prevention of mother-to-child transmission of human immunodeficiency virus (HIV) and the treatment of HIV-infected infants. Using a pooled-population approach, the pharmacokinetics of lamivudine in HIV-exposed or -infected infants from four Pediatric AIDS Clinical Trials Group studies were assessed. Ninety-nine infants provided 559 plasma samples for measurement of lamivudine concentrations. All infants received combination antiretroviral therapy including lamivudine dosed at 2 mg/kg of body weight every 12 h (q12h) for the first 4 to 6 weeks of life and at 4 mg/kg q12h thereafter. Lamivudine's apparent clearance was 0.25 liter/h/kg at birth, doubling by 28 days. In the final model, age and weight were the only significant covariates for lamivudine clearance. While lamivudine is predominantly renally eliminated, the serum creatinine level was not an independent covariate in the final model, possibly because it was confounded by age. Inclusion of interoccasion variability for bioavailability improved the individual subject clearance prediction over the age range studies. Simulations based on the final model predicted that by the age of 4 weeks, 90% of infant lamivudine concentrations with the standard 2 mg/kg dose of lamivudine fell below the adult median concentration. This population pharmacokinetic analysis affirms that adjusting the dose of lamivudine from 2 mg/kg to 4 mg/kg q12 h at the age of 4 weeks for infants with normal maturation of renal function will provide optimal lamivudine exposure, potentially contributing to more successful therapy.
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PMID:Population pharmacokinetics of lamivudine in human immunodeficiency virus-exposed and -infected infants. 1789 55

Mitochondrial toxicity induced by nucleoside reverse transcriptase inhibitors (NRTIs) has been reported to be responsible for various adverse effects. The relative impact of NRTIs on the mitochondria of human immunodeficiency virus (HIV) type 1 (HIV-1)-infected children receiving highly active antiretroviral therapy (HAART) is unknown. Mitochondrial DNA (mtDNA) levels were quantified longitudinally from peripheral blood mononuclear cells (PBMCs) in 31 HIV-1-infected children from Pediatric AIDS Clinical Trial Group Study 382 who were receiving HAART, including nelfinavir, efavirenz, and different NRTIs, and who had had undetectable plasma HIV-1 RNA levels for >2 years. The median mtDNA levels in PBMCs increased from 137 copies/cell at the baseline to 179 copies/cell at week 48 (P = 0.01) and 198 copies/cell at week 104 (P < 0.001). Before the initiation of HAART, children who received regimens containing didanosine had mtDNA levels persistently lower than those in children not receiving didanosine (106 versus 140 copies/cell; P = 0.008). During HAART, the median increase in the mtDNA level from the baseline to week 104 was the lowest in children who received regimens containing didanosine (+26 copies/cell) compared to those in children who received other regimens (+79 copies/cell) (P = 0.02). A multivariate analysis also demonstrated that didanosine, as part of HAART, was the only NRTI associated with the change in mtDNA levels (P = 0.007). Children receiving didanosine-containing antiretroviral regimens have the lowest mtDNA levels in PBMCs and may be at greater risk for long-term adverse effects due to mitochondrial toxicity. This may be of particular importance in resource-limited countries where didanosine is widely used for the treatment of HIV-infected children.
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PMID:Impact of nucleoside reverse transcriptase inhibitors on mitochondria in human immunodeficiency virus type 1-infected children receiving highly active antiretroviral therapy. 1789 56

Both the human immunodeficiency virus (HIV) and environmental stress have been independently associated with decreased cognitive functioning in children. Given that they are also known to have a strong relationship with each other, the present study sought to test the hypothesis that children in conditions of high environmental risk would be at greater risk for the cognitive complications related to immunosuppression. A retrospective review was conducted to examine the records of 141 children treated at a large pediatric AIDS clinic from 1993 to 2000. CD4+ lymphocyte levels were recorded from laboratory results and IQ scores were recorded from routine psychological evaluations. Key indicators of environmental risk were collected and combined into one measure of overall environmental risk. Pearson product moment correlations were conducted to examine the relationship between environmental risk, age-adjusted CD4 and IQ. Results indicated a significant correlation between CD4 and IQ, with higher levels of immunocompetence predicting higher IQ scores. When subjects were dichotomized based on their environmental risk score, there was no relationship between CD4 count and IQ in the low environmental risk group. In contrast, CD4 was positively associated with IQ in the high environmental risk group. It is proposed that this may be due to gp120 levels in immunocompromised children being particularly toxic to the hippocampus and cortex under conditions of high stress but not so under conditions of low stress.
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PMID:The impact of environmental risk factors on HIV-associated cognitive decline in children. 1857 71


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