PubMed Health⌕ Search

Biomedical subjects

J C Borleffs

Publications and source records attributed to J C Borleffs.

At least 37 records · Page 2Linked to original sources
PubMed1997

Evaluation of sorivudine (BV-araU) versus acyclovir in the treatment of acute localized herpes zoster in human immunodeficiency virus-infected adults. The Multinational Sorivudine Study Group.

The clinical efficacy and safety of sorivudine as treatment for acute cutaneous zoster in human immunodeficiency virus-infected adults was compared with that of acyclovir in a double-blinded randomized study. A total of 125 patients with laboratory-confirmed zoster rash present for < or =72 h were assigned treatment with either 40 mg of sorivudine once daily or 800 mg of acyclovir five times daily, both taken orally for 7 days. Patients were assessed daily until all lesions crusted and then monthly for 6 months for postherpetic neuralgia (PHN) and for 12 months for recurrent or new episodes of zoster. Sorivudine significantly shortened the median period of new vesicle formation from 3.0 to 4.0 days (log rank P = .0001). Sorivudine was effective regardless of duration of rash before treatment. Zoster recurrences and new episodes were experienced by fewer patients assigned sorivudine (11%) than acyclovir (26%, P = .037). No differences were seen in incidence, severity, or duration of either acute neuritis or PHN. Both treatments were well tolerated.

Acute Disease↗
PubMed1997

In-vitro selection of HIV-1 variants resistant to non-nucleoside reverse transcriptase inhibitors in monocyte-derived macrophages.

Unlike the selection of HIV-1 variants resistant to anti-retroviral drugs in human peripheral blood mononuclear cells and T cell lines, induction of resistance in monocyte-derived macrophages has not been widely studied. Since macrophages serve as a potential HIV-1 reservoir in humans, knowledge of the effect of anti-retroviral drugs on macrophage-tropic HIV-1 isolates may help in the design of a strategy for prolonged suppression of viral replication. In-vitro selection and drug susceptibility testing of macrophage-tropic HIV-1 variants with reduced sensitivity to two non-nucleoside reverse transcriptase inhibitors, atevirdine and delavirdine (both bis-heteroarylpiperazines), is described here. The atevirdine-resistant isolate was cross-resistant to delavirdine, and the delavirdine-resistant isolate was cross-resistant to atevirdine. Interestingly, the atevirdine-resistant isolate, but not the delavirdine-resistant isolate, was also cross-resistant to nevirapin while the inhibition of viral replication of both isolates in macrophages by zidovudine was the same as that in the parental HIV-1 strain. Nucleotide sequence analysis of the resistant macrophage-tropic HIV-1 isolates showed that the atevirdine-induced resistance was due to a single amino acid change at codon 106 and that the delavirdine-induced resistance could be attributed to an amino acid change at codon 236. This study demonstrates that monocyte-derived macrophages can be used to investigate the phenotypic and genotypic acquisition of anti-retroviral drug resistance of macrophage-tropic HIV-1.

Amino Acid Sequence↗
PubMed1997

Liposomal amphotericin B (AmBisome) compared with amphotericin B both followed by oral fluconazole in the treatment of AIDS-associated cryptococcal meningitis.

OBJECTIVE: Amphotericin B deoxycholate initial therapy and fluconazole maintenance therapy is the treatment of choice for AIDS-associated cryptococcal meningitis. However, the administration of amphotericin B is associated with considerable toxicity. A potential strategy for reducing the toxicity and increasing the therapeutic index of amphotericin B is the use of lipid formulations of this drug. DESIGN AND METHODS: HIV-infected patients with cryptococcal meningitis were randomized to treatment with either liposomal amphotericin B (AmBisome) 4 mg/kg daily or standard amphotericin B 0.7 mg/kg daily for 3 weeks, each followed by fluconazole 400 mg daily for 7 weeks. During the first 3 weeks, clinical efficacy was assessed daily. Mycological response was primarily evaluated by cerebrospinal fluid (CSF) cultures at days 7, 14, 21 and 70. RESULTS: Of the 28 evaluable patients, 15 were assigned to receive AmBisome and 13 to receive amphotericin B. Baseline characteristics were comparable. The time to and the rate of clinical response were the same in both arms. AmBisome therapy resulted in a CSF culture conversion within 7 days in six out of 15 patients versus one out of 12 amphotericin B-treated patients (P = 0.09), within 14 days in 10 out of 15 AmBisome patients versus one out of nine amphotericin B patients (P = 0.01), and within 21 days in 11 out of 15 AmBisome patients versus three out of eight amphotericin B patients (P = 0.19). When Kaplan-Meier estimates were used to compare time to CSF culture conversion, AmBisome was more effective (P < 0.05; median time between 7 and 14 days for AmBisome versus > 21 days for amphotericin B). AmBisome was significantly less nephrotoxic. CONCLUSIONS: A 3-week course of 4 mg/kg AmBisome resulted in a significantly earlier CSF culture conversion than 0.7 mg/kg amphotericin B, had equal clinical efficacy and was significantly less nephrotoxic when used for the treatment of primary episodes of AIDS-associated cryptococcal meningitis.

AIDS-Related Opportunistic Infections↗
PubMed1996

Lifetime hospitalization profiles for symptomatic, HIV-infected persons.

We explored the relationship between the incidence of hospitalization and disease progression in a group of 140 symptomatic, HIV infected patients by linking hospitalizations to the time of diagnosis, the time of death, or both. The relationship could best be described by positively skewed U-patterns or (weak) J-patterns with a high use of resources immediately following diagnosis and preceding death. The lifetime hospitalization profiles differed according to the type of insurance, age, the initial diagnosis in the CDC-IV stage and the length of survival. The results not only confirm general hypotheses posed by other research groups, but also demonstrate the existence of variations among subgroups of patients. The results can be used to improve economic assessments of the impact of AIDS in The Netherlands and the European Union. The method used has the advantage of being based on a bottom-up approach to resource utilization, involving the use pf prospective data for the patients' full lifespans, and can easily be applied to other areas of health services research.

Adult↗
PubMed1996

The influence of PCP prophylaxis on bacteriuria incidence and resistance development to trimethoprim/sulfamethoxazole in HIV-infected patients.

BACKGROUND: Earlier studies have shown that men infected with HIV-1 and a CD4+ cell count below 200 mm3 are at increased risk for bacteriuria. We studied the effect of 3 Pneumocystis carinii (PCP) prophylaxis regimens (low-dose TMP/SMZ, high-dose TMP/SMZ and pentamidine aerosol) on the incidence of bacteriuria and resistance development to TMP/SMZ. METHODS: Retrospective analysis of 103 HIV-positive patients. RESULTS: Nine patients using pentamidine had a positive culture (32%), compared to 9 patients using low-dose TMP/SMZ (17%) and 5 patients using high-dose TMP/SMZ (22%). These differences were not significant (P = 0.207). However, almost all episodes in patients using TMP/SMZ were due to infection with a resistant strain. CONCLUSION: PCP prophylaxis with trimethoprim/sulfamethoxazole does not significantly influence the rate of bacteriuria, probably due to the development of resistance.

Bacteriuria↗
PubMed1996

Human immunodeficiency virus type 1 (HIV-1)--and Epstein-Barr virus--specific cytotoxic T lymphocyte precursors exhibit different kinetics in HIV-1--infected persons.

The frequencies of human immunodeficiency virus type 1 (HIV-1) Gag- and Epstein-Barr virus (EBV)-specific cytotoxic T lymphocyte precursors (CTLp) were studied longitudinally in peripheral blood mononuclear cells from 9 HIV-1-infected persons. By antigen-specific stimulation, HIV-1 Gag-specific CTLp were detected in vitro throughout the course of HIV-1 infection, even after the onset of overt disease. In 4 patients, however, HIV-1 Gag-specific CTLp frequencies declined over time in the presence of maintained EBV-specific CTLp. This decline was correlated with decreasing CD4 (r = .38; P < .05) and CD8 (r = .75; P < .001) cell numbers. The maintenance of EBV-specific CTLp in patients with low CD4 cell numbers indicated that EBV-specific CTL-mediated immunity may remain longer unaffected by HIV-1-induced immune dysfunction. Consistent with this observation, the growth of EBV-specific CTL could be supported in vitro by EBV-infected lymphoblastoid B cell lines, independent of both CD4 cells and exogenous cytokines.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Safety, tolerance, and efficacy of atevirdine in asymptomatic human immunodeficiency virus-infected individuals.

Atevirdine is a nonnucleoside reverse transcriptase inhibitor of human immunodeficiency virus type 1 (HIV-1). In this study we investigated the effect of atevirdine in asymptomatic antiretroviral naive HIV-infected patients with CD4+ cell counts of between 200 and 750 cells per mm3. Patients were randomized to receive 600 mg of atevirdine (n = 15) or a placebo (n = 15) three times a day for 12 weeks. There was no statistically significant effect of atevirdine on viral loads (HIV p24 antigen and HIV-1 RNA levels by PCR) or CD4+ cell counts. The data do not support the use of atevirdine as a monotherapy in the treatment of HIV-infected patients.

Adult↗
PubMed1995

AIDS scenarios for The Netherlands; the economic impact on hospitals.

OBJECTIVE: To assess the economic impact of HIV/AIDS on the health care system in The Netherlands. DATA AND METHODS: Two types of data are used: (i) routine surveillance data on AIDS incidence and (ii) information on hospital resource utilisation and corresponding monetary costs. Progression of disease is modelled using a multi-stage model, with stages corresponding to clinical classifications and to different phases of health care need. Economic impact is analysed for all stages in three scenarios: the reference and two alternative scenarios. RESULTS: In the year 2000 hospital bed need would reach 220 beds if yearly new HIV infections in the 1990s remain at the level estimated for the end of the 1980s, and if the intensity of hospital care remains constant. A minimum need of 125 beds is projected if no new HIV infections occur in the 1990s. Hospital costs in 1993 are estimated to amount to 33.8 million ECUs. Scenarios indicate a range of 26.7-50.7 million ECUs for the year 2000 (price level: 1993). The proportion of the costs of hospital inpatient care and cure in total hospital costs increases, whereas the proportion for outpatient services decreases. CONCLUSIONS: Projected hospital bed need of 125-220 for HIV/AIDS in the year 2000 is limited compared to the projections for coronary heart disease and stroke, but approaches that for lung cancer, pneumonia and diabetes. We estimate hospital costs to have been 85% of total health care costs for HIV/AIDS in 1993. In 1993, the estimated proportions in hospital costs are 41% for inpatient care, 20% for inpatient cure and 39% for outpatient facilities. Our scenarios indicate a decreasing share of outpatient costs--possibly to 30% of total hospital costs for HIV/AIDS in 2000--illustrating the growing relative importance of the AIDS stage for the hospital costs. We project hospital costs for HIV/AIDS in 2000 to reach up to 0.53% of projected hospital costs for all diseases. A present value of 38 million ECUs (23%) of hospital costs projected in the reference scenario might be avoidable, during the period 1994-2000. However, with unchanged treatment patterns a present value of 127 million ECUs for hospital costs during the same period is projected to represent unavoidable costs (discount rate: 5%). In The Netherlands, data needs in the field of economic impact assessment of HIV/AIDS especially refer to registrations of non-hospital outpatient resource utilisation and costs.

Acquired Immunodeficiency Syndrome↗
PubMed1995

In-patient care for symptomatic, HIV-infected persons: a longitudinal study of hospitalizations, in-patient drug use, and related costs.

Patterns in the costs of hospital in-patient care and in-patient drug treatment of 121 symptomatic, HIV-infected patients are described for a university hospital between 1987 and 1991. Trend analyses have been performed on quarterly and yearly data using parametric and non-parametric statistical techniques. During the 5-year study period the demand for hospital beds almost quadrupled despite a constant number of admissions per person-year and a 40% decrease in the average length of stay. The demand for beds was highest in the autumn and winter months. The impact of female and/or heterosexual subgroups on the yearly utilization of resources increased and reasons for hospitalization became more diverse; there were fewer hospitalizations for Pneumocystis carinii pneumonia infection. Antimicrobial drug treatment accounted for the increased drug treatment costs. The implications for AIDS-treating specialists, hospital managers, and scenario analysts are discussed.

AIDS-Related Opportunistic Infections↗
PubMed1995

Efficacy and toxicity of two doses of trimethoprim-sulfamethoxazole as primary prophylaxis against Pneumocystis carinii pneumonia in patients with human immunodeficiency virus. Dutch AIDS Treatment Group.

The efficacy and toxicity of trimethoprim-sulfamethoxazole (TMP-SMZ) as primary prophylaxis against Pneumocystis carinii pneumonia (PCP) for patients with human immunodeficiency virus (HIV) infection was assessed by comparing the effects of two dosages (480 or 960 mg once a day) of the drug. The multicenter trial involved 260 HIV-infected patients with CD4 cell counts < 0.2 x 10(9)/L and no history of PCP. Patients were randomly assigned to the treatment groups. After a median follow-up of 376 days (range, 1-1219), none of the patients developed PCP. Most adverse reactions that required discontinuation were seen within the first month of TMP-SMZ use and were seen more frequently and earlier in the 960-mg group (hazard ratio, 1.4; 95% confidence interval, 0.95-2.02; P = .007). For patients with HIV infection, 480 mg of TMP-SMZ is as efficacious as but less toxic than 960 mg of the drug for primary prophylaxis against PCP.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Deficient antipneumococcal polysaccharide responses in HIV-seropositive patients.

In a prospective study, serological responses and opsonic activity towards Streptococcus pneumoniae were measured in 60 HIV-infected patients and 25 controls after the administration of the 23-valent pneumococcal vaccine (PneumovaxR). Serum samples were collected before vaccination and at weeks 1, 2, 4, and 12 after vaccination and were tested for the presence of antibodies against a mixture of capsular polysaccharide antigens (pool) and against type 3 and type 4 antigens (PS3 and PS4), using an ELISA. A serological response was defined as a two-fold or greater increase in serum titer after vaccination. Opsonophagocytosis was measured in patients with a definite response against PS3. Generally, prevaccination antipneumococcal antibody titers were clearly higher in HIV-infected patients than in healthy controls. After vaccination, antipool antibody responses were found in 76% of vaccinated patients; 24% of the patients were non-responders. In patients with more than 0.300 x 10(9) CD4 + cells per liter the percentage of responders was 94%; in patients with fewer than 0.300 x 10(9) CD4 + cells per liter this percentage was 68% (P < 0.05). The antipool response in control subjects was 92%. A serological response to PS3 and PS4 was found in 29% and 49% of the patients, respectively, and was correlated with CD4 + cell count. In controls, these percentages were 48% and 92%, respectively. In 30% of responding patients, antibody titers dropped already to prevaccination levels by week 12 after vaccination. Opsonophagocytosis was not significantly improved by vaccination, probably because of a relatively high preexisting opsonic activity. Although prevaccination conditions may have had an important influence on the study outcome, the results are not in favor of a significant beneficial effect of vaccination with PneumovaxR on antibody formation in HIV-infected patients. This raises further questions as to the relevance of pneumococcal vaccination in this population.

Antibodies, Bacterial↗
PubMed1995

Safety, tolerance, and pharmacokinetics of atevirdine mesylate (U-87201E) in asymptomatic human immunodeficiency virus-infected patients.

Atevirdine mesylate (U-87201E) is a new nonnucleoside (bisheteroarylpiperazine) inhibitor of human immunodeficiency virus type 1 reverse transcriptase. In a double-blind, escalating single-dose study the safety, tolerance, and pharmacokinetics of atevirdine mesylate were investigated in 24 asymptomatic human immunodeficiency virus-seropositive male patients. Each patient received one single oral dose of atevirdine mesylate and placebo separated by an interval of 1 to 3 weeks. For each dose level (400, 800, 1,200, and 1,600 mg) six patients received drug and placebo on separate occasions. Blood samples were collected before dosing and at intervals afterward for safety evaluation and estimation of atevirdine and metabolite levels. The concentrations of atevirdine and its principal metabolite (U-89255) in serum were determined by high-performance liquid chromatography. The results of the study showed that atevirdine mesylate is well tolerated at all dose levels. No clinically significant effects on vital signs, electrocardiograms, or laboratory tests were observed. Occasional headache and nausea were reported both in the drug group and in the placebo group. The times to peak values were relatively short (0.5 to 1.0 h), suggesting a rapid absorption. The maximum concentrations of drug in serum were 1.4 microM (400 mg), 4.2 microM (800 mg), 7.3 microM (1,200 mg), and 5.8 microM (1,600 mg). The values of the pharmacokinetic parameters for atevirdine were found to have relatively large intersubject variabilities, and consequently, the study had little power to detect dose-dependent changes in the values of the pharmacokinetic parameters. The oral clearance of atevirdine tended to increase by 90% as the atevirdine mesylate doses increased from 400 to 1,600 mg, but this change in oral clearance was not statistically significant. The values of the pharmacokinetic parameters determined in the study were similar to those found in a previous single-dose study in healthy volunteers.

Adult↗
PubMed1994

[Rhodococcus equi pneumonia in patients with immunodeficiency].

In three patients, men of 30, 21 and 24 years old respectively, Rhodococcus equi pneumonia was diagnosed. Antibiotic treatment, followed by secondary prophylaxis, was successful. In one patient, lobectomy was done. R. equi, a well-known bacterial pathogen in horses, appears also to be pathogenic in humans in case of immunodeficiency.

AIDS-Related Opportunistic Infections↗
PubMed1994

Trends in hospital resource utilization by HIV-infected persons, January 1987-June 1990.

Trends in the utilization of various hospital resources by HIV-infected persons between January 1987 and June 1990 have been studied to support health care planning. Data on 126 asymptomatic and symptomatic HIV-infected persons have been recorded at a patient level and analyzed at half-yearly intervals. At a hospital level, increasing utilization trends were observed. At the patient level, a decreasing utilization intensity was measured for admissions, inpatient days, inpatient diagnostic examinations, and outpatient consultations. Increasing utilization intensity was measured for care during admissions. A constant utilization intensity was observed for outpatient diagnostic examinations and inpatient medication days. Use of interventions tended to increase at the end of the study period. Discriminating between trends in the utilization of different hospital resources can improve the management of hospital health care demands of HIV-infected people.

Adult↗
PubMed1994

Kinetics and specificities of the T helper-cell response to gp120 in the asymptomatic stage of HIV-1 infection.

Peripheral blood mononuclear cells from 36 asymptomatic HIV-1 seropositive individuals were tested longitudinally for in vitro T-cell proliferation and IL-2 production in response to synthetic peptides spanning the entire gp120 of HIV-1. At baseline, significant T-cell proliferative to pooled and individual peptides was observed in 15 of the 36 donors. After 12 months, proliferative responses to peptide pools were lost or decreased significantly in most donors. Responses appeared to fluctuate over time: at 12 months new recognition sites were detected in four of 10 donors showing T-cell proliferation at baseline, as well as in five of 15 donors with no previous proliferative responses. IL-2 production appeared to be a more sensitive and longer preserved parameter of T-helper cell function: at baseline the majority of donors with no T-cell proliferation produced IL-2 in response to pooled peptides. This response was not decreased significantly after 12 months. The overall patterns of response to both pooled and individual peptides were heterogeneous among donors. Multiple recognition sites were detected in both variable and conserved regions of gp120, but no pool or individual peptide was recognized by all responders. Functional T-cell responses were not statistically correlated to CD4+ cell percentile and absolute numbers.

Adult↗
PubMed1994

Routine vaccination in HIV-infected patients: a review.

This paper reviews the literature from 1988 to November 1993 on the effectiveness of routine vaccination of HIV-infected adults. Data on the clinical benefit of vaccination in this particular group of patients are not available. In general, HIV-infected patients have suboptimal immunological responses to vaccines. In particular, an impaired responsiveness is found in patients with fewer than 200 x 10(6) CD4+ cells per litre. Consequently, it seems prudent to offer active immunization to HIV-infected subjects who are relatively immunocompetent. However, the usefulness of vaccination in those subjects who have a low CD4+ cell count is doubtful.

HIV Infections↗
PubMed1993

Non-radioactive PCR method for quantification of HIV-infected peripheral blood mononuclear cells in HIV-positive subjects.

A nested PCR method for quantification of HIV-infected peripheral blood mononuclear cells (PBMC) which does not use radioactivity nor plasmids is described. Quantification was achieved by means of limiting dilutions and an ACH2 cell standard. The method was used to study 23 HIV-infected patients. A significant correlation was seen between the stage of HIV disease, as classified by CDC criteria, and the number of infected PBMC. Although the CD4+ cell count also correlated well with the stage of HIV disease, there was only weak correlation between the result obtained by the PCR method and the CD4+ cell count.

Base Sequence↗