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H J Scherpbier

Publications and source records attributed to H J Scherpbier.

At least 19 recordsLinked to original sources
PubMed2004

[Treatment of HIV-1 infected pregnant women].

Since 1 January 2004, pregnant women in the Netherlands have been universally screened for HIV infection. Three HIV-infected, pregnant women aged 28, 24 and 33 years respectively, illustrate some of the problems that may be encountered in this situation, as well as the treatment options available to prevent the transmission of HIV from mother to child. The first patient had a positive antibody test early in pregnancy for which she did not need treatment, the second had a positive antibody test late in pregnancy and the third was seropositive and on medication, but had the wish to become pregnant. A vaginal delivery is possible when highly active antiretroviral therapy (HAART) of the mother is started in good time and the plasma HIV-RNA is < 400 copies/ml at the time of delivery. In this situation the risk of transmission is reduced to around 1%. However, if HIV infection is diagnosed late in pregnancy or, despite HAART, the plasma HIV-RNA is not expected to be < 400 copies/ml, an elective caesarean section is scheduled at 38 weeks of pregnancy. In all instances the neonate is treated for 28 days with antiretrovirals, as post-exposure prophylaxis. If a woman with a known HIV infection wants to become pregnant, the choice of antiretroviral regimen and when this is started is determined by her treatment history and the potential toxic effects of the medication on the foetus.

Adult↗
PubMed2002

[Reduction of vertical transmission by means of perinatal prophylaxis in the case of children exposed to HIV-1 and born in the Netherlands during the period 1995-1999].

OBJECTIVE: Registration of the number of children born to HIV-infected mothers diagnosed prepartum and analysis of the efficacy of the policy for preventing mother-to-child transmission of HIV-1 in the period 1995 to 1999. DESIGN: Prospective. METHOD: On a monthly basis, Dutch paediatricians reported HIV-1 exposed children to the Dutch Paediatric Surveillance Unit. All reports were followed up with standard questionnaires. An additional retrospective study was performed because of incomplete registration. Paediatricians in centres for the care of HIV-infected patients were requested to retrospectively report HIV-exposed children. The standard questionnaires were submitted to these paediatricians. Data were collected during the period 1 January 1995-31 December 1999. RESULTS: The number of children known to be exposed to HIV-1 and for whom the mother was diagnosed prepartum, increased from 5 to 25 per year. The percentage of HIV-1 infected children decreased from 20% (1/5) to 4% (1/25). The number of pregnant HIV-1 infected women using highly active antiretroviral therapy increased during the study period from 0% (0/5) to 72% (18/25). Antiretroviral therapy was administered to 92% (23/25) of HIV-1 exposed children. In total 2% of the children received breastfeeding. CONCLUSION: Despite an increase in the number of children known to be exposed to HIV-1, a decrease in the percentage of HIV-1-infected children was observed. Of the children born in 1999 and known to be exposed to HIV-1, 4% were infected. Measures taken in the Netherlands to prevent mother-to-child transmission of HIV-1 infection are effective.

Antiretroviral Therapy, Highly Active↗
PubMed2001

Therapeutic immune reconstitution in HIV-1-infected children is independent of their age and pretreatment immune status.

OBJECTIVE: To evaluate long-term immune reconstitution of children treated with highly active antiretroviral therapy (HAART). METHODS: The long-term immunological response to HAART was studied in 71 HIV-1-infected children (aged 1 month to 18 years) in two prospective, open, uncontrolled national multicentre studies. Blood samples were taken before and after HAART was initiated, with a follow-up of 96 weeks, and peripheral CD4 and CD8 T cells plus naive and memory subsets were identified in whole blood samples. Relative cell counts were calculated in relation to the median of the age-specific reference. RESULTS: The absolute CD4 cell count and percentage and the CD4 cell count as a percentage of normal increased significantly (P < 0.001) to medians of 939 x 106 cells/l (range, 10-3520), 32% (range, 1-50) and 84% (range, 1-161), respectively, after 48 weeks. This increase was predominantly owing to naive CD4 T cells. There was a correlation between the increase of absolute naive CD4 T cell counts and age. However, when CD4 T cell restoration was studied as percentage of normal values, the inverse correlation between the increase of naive CD4 T cell count and age was not observed. In addition, no difference in immunological reconstitution was observed at any time point between virological responders and non-responders. CONCLUSIONS: Normalization of the CD4 cell counts in children treated with HAART is independent of age, indicating that children of all age groups can meet their CD4 T cell production demands. In general, it appears that children restore their CD4 T cell counts better and more rapidly than adults, even in a late stage of HIV-1 infection.

Adolescent↗
PubMed2001

Pharmacokinetics of the protease inhibitor indinavir in human immunodeficiency virus type 1-infected children.

The objective of this study was to evaluate the pharmacokinetics of indinavir in human immunodeficiency virus-infected children as part of a prospective, open, uncontrolled, multicenter study in The Netherlands. Human immunodeficiency virus type 1-infected children were monitored over 6 months of treatment with zidovudine (120 mg/m(2) every 8 h [q8h]), lamivudine (4 mg/kg of body weight q12h), and indinavir (33mg/kg of metabolic weight [MW] q8h). Four weeks after the start of treatment, the steady-state pharmacokinetics of indinavir were determined by high-pressure liquid chromatography. If patients had an indinavir area under the concentration-time curve (AUC) of below 10 or above 30 mg/liter. h, a dose increase or a dose reduction was made and pharmacokinetic measurements were repeated 4 weeks later. Nineteen patients started with the dose of 33 mg/kg of MW q8h. The median AUC (range) was 10.5 (2.8 to 51.0) mg/liter. h. The median AUC (range) in 17 children treated with 50 mg/kg of MW q8h was 20.6 (4.1 to 38.7) mg/liter. h. Finally, five patients had a dose increase to 67 mg/kg of MW q8h, resulting in a median AUC (range) of 36.6 (27.2 to 80.0) mg/liter. h. After 6 months of treatment, there were 11 children with an AUC of below 20 mg/liter. h, of whom 5 (45%) had a detectable viral load, while this was the case in none of the 11 children with an AUC of higher than 20 mg/liter. h. We conclude that the optimal dose of indinavir in children to obtain drug exposure similar to that observed in adult patients is 50 mg/kg of MW q8h, which approximates 600 mg/m(2) q8h. It would even be better to adjust the indinavir dose based on an AUC of greater than 20 mg/liter. h.

Adolescent↗
PubMed2000

Clinical and virologic response to combination treatment with indinavir, zidovudine, and lamivudine in children with human immunodeficiency virus-1 infection: a multicenter study in the Netherlands. On behalf of the Dutch Study Group for Children with HIV-1 infections.

OBJECTIVE: To evaluate the clinical, immunologic, and virologic response to indinavir, zidovudine, and lamivudine in children with human immunodeficiency virus-1 (HIV-1) infection. STUDY DESIGN: Twenty-eight HIV-1-infected children (3 months to 16 years of age) with or without prior treatment with reverse-transcriptase inhibitors and a HIV-1 RNA >5000 copies/mL and/or a CD4 cell count less than the lower limit of the age-specific reference value were treated with indinavir, zidovudine, and lamivudine. Pharmacokinetics of indinavir were determined in each child. RESULTS: The combination treatment was well tolerated in the majority of patients. Clinical improvement was seen in all patients. After 6 months of therapy, 70% of the patients had an HIV-1 RNA load below 500 copies/mL, whereas 48% of the children had a viral load below 40 copies/mL. Relative CD4 cell counts in relation to the lower limit of the age-specific reference value increased significantly from a median value of 79% at baseline to 106% after 6 months of therapy. The doses of indinavir necessary to achieve area under the curve values comparable to adult values varied from 1250 mg/m(2)/d to 2450 mg/m(2)/d. CONCLUSIONS: Highly active antiretroviral therapy consisting of indinavir, zidovudine, and lamivudine in children reduced HIV-1 RNA to less than 500 copies/mL in 70% of the children within 6 months. Improved CD4 cell counts were observed in most patients, as was a better clinical condition (no invasive or opportunistic infections, increased weight gain). Side effects of the triple therapy were mild. Highly active antiretroviral therapy can be used as successfully in children as in adults.

Adolescent↗
PubMed1998

Early recovery of CD4+ T lymphocytes in children on highly active antiretroviral therapy. Dutch study group for children with HIV infections.

INTRODUCTION: Regeneration of CD4+ T lymphocytes has been shown to be thymus-dependent in bone marrow transplant recipients and after intensive chemotherapy. The rate of CD4+ T cell regeneration is correlated positively with enlargement of the thymus, as shown on radiographs, and higher rates of CD4+ T lymphocyte regeneration were observed in children as compared with adults, consistent with thymic function diminishing with age. We hypothesized that in HIV infected patients CD4+ T cell recovery during highly active antiretroviral therapy (HAART) may also be thymus dependent. Therefore, repopulation of naive (CD45RA+), memory (CD45RO+) and total CD4+ T lymphocytes and total CD8+ T lymphocytes in peripheral blood was assessed in 13 HIV infected children during the initial 3 months of HAART. RESULTS: Significantly higher recovery rates of naive, memory and total CD4+ T cells were observed in children below the age of 3 years as compared with older children. Kinetics of total CD8+ T cells showed no relation to age. Moreover, recovery rates of naive CD4+ T cells in patients below 3 years of age were 10-40 fold higher as compared with previously reported naive CD4+ T cell recovery rates in adults on HAART. CONCLUSIONS: High recovery rates of naive, memory and total CD4+ T cells can be achieved in children below 3 years of age. Changes in CD8 counts did not correlate with age. These results indicate that regeneration of CD4+ T cells during HAART may be a thymus-dependent process.

Adolescent↗
PubMed1995

Similarity in env and gag genes between genomic RNAs of human immunodeficiency virus type 1 (HIV-1) from mother and infant is unrelated to time of HIV-1 RNA positivity in the child.

Variation in the env (V3 region) and gag (p17 region) genes of genomic RNA of human immunodeficiency virus type 1 was studied in three mother-child pairs. One infant was human immunodeficiency virus type 1 RNA positive at birth (pair 114), one became positive 6 weeks after birth (pair 127), and one became positive 30 months after birth (pair 564). The first two children were born to seropositive mothers, and the last child was infected by breast-feeding following seroconversion of the mother after delivery. In both V3 and p17gag, intrasample variability was much higher in the maternal samples, including the first seropositive sample of the seroconverted mother, than in the infants' samples. Variability was less in p17gag than in V3, except in the postnatally infected child. In all three cases, infection of the child was established by variants representing a minority of the cell-free virus population in the maternal samples. For the two infants born to seropositive mothers, V3 sequences were more similar to the sequence populations of maternal samples collected during pregnancy than to those of samples collected at delivery or thereafter. However, in pair 114 a V3 variant identical to the child's virus was also detected in the sample collected at delivery. In contrast to the V3 region, p17gag sequences of maternal samples of the first trimester of pregnancy and at delivery had comparable resemblance to the child's sequences in pair 114, while in pair 127, similarity to sequences of the sample collected at delivery was higher than that to sequences of the sample from early in pregnancy. In the last pair, V3 and p17gag sequences from a maternal sample collected 18 months prior to the first RNA-positive sample of the child resembled the infant's sequences as much as the sample collected close to the presumed time of infection. Taken together, the evolutionary characteristics for genomic RNA env and gag genes did not point to a particular time of mother-to-child transmission.

Amino Acid Sequence↗
PubMed1995

Computerized pharmacokinetics on an institutional clinical information system.

Computer-based hospital information systems (HISs) are an integral part of the current hospital environment. Traditionally, the HIS hospital information system has performed drug distribution-related activities for the pharmacy. Clinical applications have been limited to monitoring for drug interactions, duplication of therapy, drug allergies, and dosage range checking. Personal computers have been used for more clinical applications and individualized dosing. At Hamot Medical Center, the integration of the pharmacokinetics consultation service with the HIS has been accomplished. The pharmacokinetic equations were programmed into the HIS. Data needed for the equations were extracted from information in the database, thereby eliminating the need to enter the majority of the data. The program was designed to print the pharmacokinetic consultation for the chart. The integration of the pharmacokinetic consultation service with the HIS has saved time and increased efficiency.

Clinical Pharmacy Information Systems↗
PubMed1994

Macrophage-tropic variants initiate human immunodeficiency virus type 1 infection after sexual, parenteral, and vertical transmission.

Macrophage-tropic, non-syncytium-inducing, HIV-1 variants predominate in the asymptomatic phase of infection and may be responsible for establishing infection in an individual exposed to the mixture of HIV-1 variants. Here, genotypical and phenotypical characteristics of virus populations, present in sexual, parenteral, or vertical donor-recipient pairs, were studied. Sequence analysis of the V3 domain confirmed the presence of a homogeneous virus population in recently infected individuals. Biological HIV-1 clones were further characterized for syncytium inducing capacity on the MT2 cell line and for macrophage tropism as defined by the appearance of proviral DNA upon inoculation of monocyte-derived macrophages. Both sexual and parenteral transmission cases revealed a selective outgrowth in the recipient of the most macrophage-tropic variant(s) present in the donor. In three out of five vertical transmission cases, more than one highly macrophage-tropic virus variant was present in the child shortly after birth, suggestive of transmission of multiple variants. In three primary infection cases, homogeneous virus populations of macrophage-tropic, non-syncytium-inducing variants were present prior to seroconversion, thus excluding humoral immunity as the selective pressure in favour of macrophage-tropic variants. These observations may have important implications for vaccine development.

Acquired Immunodeficiency Syndrome↗
PubMed1994

A simple approach to physician entry of patient problem list.

The patient's problem list is one of the key components of the electronic medical record. Besides the immediate benefits of using the patient problem list for medical records coding and creation of discharge documentation, a coded problem list is a prerequisite of patient management, clinical decision support and research. The ICD9 coding system that is the current standard for coding diagnoses and procedures is not conducive to physician usage. In this paper we describe a simple system that provides physicians with a quick and easy method to enter and maintain a patient's problem list. Physicians can use their own terminology. ICD9 codes are included where possible, but free text is allowed. The system strikes a balance between capturing a fully coded patient problem list and encouraging usage by a wide physician user group.

Diagnosis-Related Groups↗
PubMed1993

[The treatment of 12 HIV-infected children with zidovudine].

12 HIV-infected children were treated with a high dose of zidovudine (800/mg/m2/day) during a mean follow up period of 18 months. After starting treatment with zidovudine there was a subjective improvement and an increase in body weight, and a significant decline in serum HIV-antigenemia (p < 0.01) and serum IgG levels (p < 0.05). Zidovudine was generally well tolerated but there was serious hematological toxicity. In 9 patients (75%) dose reduction was necessary because of severe anemia (3 patients) or leucopenia (6 patients). Because of the high incidence of these side effects the starting dose of zidovudine was reduced to 600 mg/m2/day. These results confirm that zidovudine can safely be used to treat HIV-infected children. The main limitation is serious hematological toxicity which appears to be dose-related.

AIDS-Related Opportunistic Infections↗
PubMed1993

Genomic human immunodeficiency virus type 1 RNA variation in mother and child following intra-uterine virus transmission.

In order to study the relationship between virus populations in a human immunodeficiency virus type 1 (HIV-1)-infected mother and her infant, we analysed a 276 bp fragment, including the V3 region, of genomic HIV-1 RNA purified from serum. Samples were collected from the mother 6, 4 and 2 months prior to delivery, during delivery and 10 months after childbirth (samples MA to ME, respectively) and from the infant at birth (cord blood) and the ages of 6 weeks and 9 months. A heterogeneous sequence population was observed in the maternal samples (mean nucleotide variation of 2.4 to 4.2%, range 0 to 8.3%). Until the age of 6 weeks the sequence population in the infant was highly homogeneous (mean nucleotide variation < or = 0.7%, range 0 to 2.5%). At 9 months of age, the infant's virus population showed more heterogeneity (mean nucleotide variation of 1.8%, range 0.4 to 3.6%) and a drift in the consensus sequence was observed. The evolution of the V3 region in the mother was characterized by accumulation of amino acid substitutions diverging from the virus population observed in the infant. The mean nucleotide distance between the maternal sequence populations and the sequence population of the child at birth was 2.8, 2.6, 3.7, 5.2 and 5.3% for the samples MA, MB, MC, MD and ME, respectively. Nearly complete replacement at position 308, previously described as antigenically important, from a proline to a histidine was observed during pregnancy, whereas all clones of the child's virus at birth and at 6 weeks contained a proline at that position. In conclusion, intra-uterine transmission is associated with a homogeneous sequence population in the child at birth, which is more closely related to the sequence population present in the mother during the first and second trimester of pregnancy than to the sequence population at delivery.

Acquired Immunodeficiency Syndrome↗
PubMed1992

[HIV infection in pregnant women in The Netherlands].

A review is given of the pregnant women with HIV infection known to the co-ordinating centre of the 'Dutch prospective study of HIV seropositive pregnant women and their children'. Fifty-five women with 57 pregnancies were discovered between 1 September 1985 and 1 January 1991. Of these women, 60% were not of Dutch origin and 56% were living in Amsterdam. Thirty-two women were (former) intravenous drug users. In 23 women heterosexual transmission was likely; two women were also blood transfusion recipients. Nearly half (11/23) of these women came from, or had a partner from, an AIDS-endemic area. In 16 women HIV seropositivity was known before pregnancy. Twenty-four women were specifically tested during pregnancy or within 1 week after parturition because of risk factors for HIV infection. Fifteen women were discovered in a HIV screening programme of pregnant women in Amsterdam (n = 13) and the University Hospital of Groningen (n = 2). At first, eight of these women did not mention risk factors. Thirty-five women could choose abortion (less than or equal to 20 weeks of gestation); the majority (69%) decided to continue pregnancy. Twelve pregnancies ended in an elective or spontaneous abortion, 39 in the birth of 40 children (one pair of twins) of whom 39 were viable, three women were still pregnant and of three the pregnancy outcome was unknown. Preterm delivery (8/39) and birth weight less than 2500 gram (7/39) were seen frequently, the latter particularly in women (formerly) using intravenous drugs (6/25).

Adult↗
PubMed1990

[HIV infections in childhood].

After the presentation of 3 case histories of children who became infected with HIV through different modes of transmission the disease is further discussed. Special attention is paid on epidemiology, transmission pathways, pathophysiology, making the diagnosis, clinical symptoms, therapy and prognosis of HIV infected children.

Adolescent↗
PubMed1988

[AIDS in children].

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Acquired Immunodeficiency Syndrome↗