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J J de Jong

Publications and source records attributed to J J de Jong.

16 recordsLinked to original sources
PubMed2006

A new HBsAg screening assay designed for sensitive detection of HBsAg subtypes and variants.

The design of a new HBsAg screening assay, the Hepanostika HBsAg Ultra is based on the use of monoclonal antibodies raised against native wild-type HBsAg and reactive with HBsAg in which the common 'a'-determinant is modified by site-directed mutagenesis of four of the cysteine moieties. The design was checked using the same cysteine variants and samples from patients known to be infected with HBsAg variants. The results found were compared with other state-of-the-art commercial screening assays. The design of the Hepanostika HBsAg Ultra enabled detection of all variant HBsAg-positive samples in contrast to the other commercial assays. An additional 980 samples were tested to assess the specificity and sensitivity of the Hepanostika HBsAg Ultra. Screening of presumed negative serum and plasma samples resulted in a specificity of 100%. This makes the Hepanostika HBsAg Ultra the first screening assay with a design able to detect HBsAg variants with high sensitivity and specificity.

Animals↗
PubMed2001

Potent antiretroviral therapy initiates normalization of hypergammaglobulinemia and a decline in HIV type 1-specific antibody responses.

Next to a profound T cell immunodeficiency, HIV-1 infection induces activation and dysfunction of B cells, resulting in hypergammaglobulinemia. Whereas T cell immune reconstitution with potent antiretroviral therapy has been extensively documented, limited data are available on B cell immune reconstitution. We studied the effect of potent antiretroviral therapy on antibody titers to the viral proteins gp120 and p24 and on total IgG concentrations. Three retrospectively chosen groups were studied: a successfully treated group, untreated controls, and subjects with virological failure after several months of successful therapy. In the successfully treated group, the median total IgG concentrations normalized, whereas they remained elevated in the untreated group and rebounded after an initial decline in the therapy failure group. The HIV-1-specific antibody titers declined in the successfully treated group and followed the rebound of the HIV RNA levels in the therapy failure group. With potent antiretroviral therapy the hypergammaglobulinemia normalized whereas HIV-1-specific immune responses were weakened. The weakening of antiviral immunity with therapy may be relevant for current attempts to gain immunological control over the virus through structured treatment interruptions or therapeutic vaccinations.

Adult↗
PubMed2000

Epidemiology of HIV-1 and emerging problems.

Broad use of antiretroviral drugs is becoming a factor that is important to consider for understanding the HIV-1 epidemiology. Since 1993, we observe that a proportion of new infections within major risk groups in Amsterdam is caused by azidothymidine (AZT)-resistant viruses. After the introduction of combination therapy in The Netherlands in 1997, new infections with drug-resistant viruses have not been documented. Large-scale monitoring of anti-HIV-1 therapy failures revealed that antiretroviral drugs may yield previously undescribed resistant viruses, which contain a two amino acid insertion (68SS/V69) within their reverse transcriptase genes in combination with mutations at codons 67 and 215. These viruses are highly resistant to AZT, 3TC, and d4T, and moderately resistant to ddI and ddC.

Amino Acid Sequence↗
PubMed1999

Insertion of two amino acids combined with changes in reverse transcriptase containing tyrosine-215 of HIV-1 resistant to multiple nucleoside analogs.

OBJECTIVE: To identify genotypic drug resistance patterns of HIV-1 in patients who were extensively pretreated with anti-HIV drugs and not responding to their current antiretroviral combination therapy. METHODS: Drug susceptibility of the viruses was tested by a phenotypic recombinant virus assay. Genotypic analysis of HIV resistance was performed by sequencing of the amino-terminal part of the corresponding reverse transcriptase (RT) gene (amino acids 1-280) for serum-derived and recombinant viruses. RESULTS: Among viruses from 92 patients studied, three (3%) viruses contained a T215Y amino-acid change as well as a previously unseen combination of an amino-acid change at codon 67 (N-->E/S) and a two amino-acid insertion between codons 68 and 69 of the RT gene of HIV-1. Phenotypic resistance analysis showed high levels of resistance to zidovudine, lamivudine and stavudine (in all patients) and moderate levels of resistance to didanosine and zalcitabine (in two patients), whereas neither serum-derived nor recombinant viruses contained previously known amino-acid changes conferring resistance to didanosine, zalcitabine, lamivudine and stavudine. However, all recombinant viruses contained an insertion of two amino acids between codons 68 and 69 of RT as well as an amino-acid change at codon 67, as was seen in the serum-derived viruses. CONCLUSIONS: Antiretroviral therapy including zidovudine may yield replicating viruses with a two amino-acid insertion in RT in combination with amino-acid changes at codons 67 and 215, which are highly resistant to lamivudine and stavudine on top of zidovudine and have unpredictable susceptibility to didanosine and zalcitabine despite lack of previously reported corresponding resistance-associated amino-acid changes. It is currently unknown what regimens can induce the emergence of this type of multidrug-resistant viruses. This will only be elucidated when resistance assays are capable of detecting these mutants.

Adult↗
PubMed1999

Atypical mycobacterium infection with dermatological manifestation in a renal transplant recipient.

In April 1997, a 58-year-old renal transplant recipient presented with abscess-like nodules in his left calf and on his right foot. Furuncular disease was suspected and the patient was treated with flucloxacillin. However, the lesions increased in size and became ulcerative. In the following 3 months, cultures of punctuated material, blood, and urine remained negative and gram stains did not reveal micro-organisms. In June 1997, acid-fast stains were positive. A diagnosis of a nontuberculous mycobacterium (NTM) infection was made and empirical antimycobacterial therapy was started. The combination of relatively minor symptoms with enlarged purulent lesions, causing severe morbidity, raises the possibility of NTM infection in the immunocompromised patient.

Clarithromycin↗
PubMed1998

An open randomized controlled trial of zidovudine plus lamivudine versus stavudine plus lamivudine.

OBJECTIVE: To compare the antiretroviral effect and safety of zidovudine (ZDV)-lamivudine (3TC) with that of stavudine (d4T)-3TC. METHODS: In an open randomized controlled trial antiretroviral therapy-naive patients who had CD4+ counts > or = 200 x 10(6)/l and plasma HIV RNA load > or = 10000 copies/ml were randomized to receive ZDV-3TC (200 mg three times daily and 150 mg twice daily, respectively) or d4T-3TC (40 mg and 150 mg, both twice daily). If the plasma HIV RNA level at week 8 or thereafter was > 500 copes/ml, indinavir was added at the next scheduled visit. Genotypic resistance analysis of the reverse transcriptase gene was performed at week 0 and 12. Results over 24 weeks were reported. RESULTS: Forty-seven patients were treated (24 took ZDV-3TC; 23 took d4T-3TC). Plasma HIV RNA levels decreased from median 4.80 to 3.15 log10 copies/ml (ZDV-3TC, P < 0.0001) and from 4.98 to 3.03 log10 copies/ml (d4T-3TC, P < 0.0001) after 12 weeks of treatment. Indinavir was added at week 12 in 11 out of 21 patients with ZDV-3TC and in 10 out of 22 patients with d4T-3TC. Median virus load at week 24 was 2.41 log10 and 2.29 log10 copies/ml (P=0.14), respectively. Seventy-five per cent (15 out of 20; ZDV-3TC) and 95% (18 out of 19; d4T-3TC) of patients had a virus load of < 500 copies/ml. Genomic evidence for 3TC resistance was found in all patients tested (11/11 ZDV-3TC and 12/12 d4T-3TC). At week 12, CD4 cell counts had increased with a median of 110 x 10(6)/l in the ZDV-3TC group (baseline, 315 x 10(6)/l) and a median of 115 x 10(6)/l in the d4T-3TC group (baseline 290 x 10(6)/l). At week 24, the median increases were 90 and 120 x 10(6)/l, respectively. Overall the increase of CD4+ cells was higher in the d4T-3TC group (P=0.02). CONCLUSION: d4T-3TC is at least as effective as ZDV-3TC, but 3TC resistance emerged in all patients investigated. The virological response of the dual nucleoside combination is of short duration. However, after addition of indinavir the virus load could be reduced to < 500 copies/ml in the majority of patients. The increase in CD4+ cell count was significantly greater in the d4T-3TC group. To prevent 3TC resistance, the drug should not be used in regimens containing only two nucleosides, irrespective the virus load at baseline.

Adult↗
PubMed1998

[Virological evaluation of treating HIV-infected patients with (combinations of) antiretroviral drugs at the Amsterdam Academic Medical Center, 1996/'97].

OBJECTIVE: First clinical virological evaluation of anti-HIV treatment with HIV reverse transcriptase (RT) and protease inhibitors. DESIGN: Descriptive. SETTING: Academic Medical Centre of the University of Amsterdam, the Netherlands. METHOD: From January 1, 1996, until May 1, 1997, HIV-RNA levels were determined in sequential serum or plasma samples obtained sequentially of 384 patients over a period of 3.1 years on average (minimum 0.5, maximum 10 years). Of these patients 318 had sustained treatment for at least 6 months. The effect on HIV-RNA serum or plasma levels was evaluated in this particular group, of which 224 (70.4%) had been pretreated with antiretroviral drugs (experienced patients) and 94 (29.6%) had not (naive patients). RESULTS: Of the naive patients 8.5% were treated with a combination of two, 89.4% with three and 2.1% with four anti-HIV drugs. Preceding their current treatment, an average of more than two other anti-HIV regimens had been administered to the experienced patients. From 1987 until May 1997 a total of 834 treatments were registered among the 224 patients: 202 mono, 223 double, 340 triple, 60 quadruple and 9 other combination treatments. After six months 84% of the triple combination treatments in the naive patients and 61% in the experienced patients resulted in RNA levels < or = 10(3) copies/ml (p = 0.008). Of 68 patients who failed on treatment 36 (52.9%) showed resistance associated mutations in HIV reverse transcriptase. In 6/43 (14%) of these patients resistance associated mutations in protease were found as well. Genotypic resistance could not always be confirmed phenotypically. CONCLUSION: Our preliminary results indicate that in a majority of cases triple combination treatment including at least one HIV protease inhibitor was successful. Nevertheless, in 16% of the therapy-naive and 39% of the therapy-experienced patients the anti-HIV effect of treatment was insufficient.

Antiviral Agents↗
PubMed1998

Decrease of HIV-1 RNA levels in lymphoid tissue and peripheral blood during treatment with ritonavir, lamivudine and zidovudine. Ritonavir/3TC/ZDV Study Group.

OBJECTIVES: Triple combination treatment of HIV-1 infection using two reverse transcriptase inhibitors and a protease inhibitor can result in significant and sustained decreases in the quantity of viral RNA in peripheral blood. Lymphoid tissue, however, constitutes the major reservoir of HIV in infected patients. Study of the viral burden in these tissues has provided additional insight in the efficacy of antiretroviral treatment. DESIGN: Patients were randomized into two groups in order to study differences in the development of resistance to reverse transcriptase inhibitors. Group I started treatment with all three drugs simultaneously. Group II started with ritonavir monotherapy, aiming at initial reduction in virus production before the addition of lamivudine and zidovudine 3 weeks later. METHODS: Changes in the amount of HIV in plasma and tonsillar lymphoid tissue during 24 weeks of treatment with ritonavir, lamivudine and zidovudine were studied by reverse transcriptase polymerase chain reaction. RESULTS: Thirty-three antiretroviral-naive HIV-infected patients were included for analysis. After 24 weeks, median CD4+ cell count increased by 152 x 10(6)/l and median plasma viral RNA levels decreased by at least 2.87 log10 copies/ml. In 88% of the patients remaining on treatment, plasma RNA levels were below the quantification limit of the assay used (mean, 2.4 log10 copies/ml). The lymphoid tissue viral burden, ranging from 9.16 to 8.52 log10 copies/g at baseline, was markedly reduced with at least 2.1 log10 copies/g by week 24 in the five patients analysed. Eight patients (24%) withdrew because of side-effects. In one patient in group II, ritonavir and lamivudine resistance-associated mutations developed. CONCLUSIONS: Treatment with this triple antiretroviral drug combination produced a durable and strong decrease of HIV-1 RNA burden in both plasma and lymphoid tissue.

Adult↗
PubMed1997

[Zidovudine-resistant HIV strains in untreated intravenous drug users and homosexual men in Amsterdam infected in 1996].

OBJECTIVE: To gain insight into the spread of HIV strains with different sensitivities to antiretroviral drugs prescribed in the Netherlands. DESIGN: Prospective cohort study in intravenous drug users and homosexual men. SETTING: Amsterdam, the Netherlands. METHODS: HIV negative participants in the Amsterdam cohort studies among homosexual men and intravenous drug users are tested two to three times a year for HIV antibodies. The first positive serum sample of those who seroconverted was used to determine, on the basis of the nucleotide sequence of the reverse transcriptase gene of HIV, if viruses were present with a reduced sensitivity to reverse transcriptase inhibitors. RESULTS: In 1996, 17 new HIV infections occurred (8 in homosexual men and 9 in intravenous drug users). In two new infections in homosexual men HIV strains with reduced sensitivity to zidovudine were present.

Anti-HIV Agents↗
PubMed1997

Refocusing neutralizing antibody response by targeted dampening of an immunodominant epitope.

Immunodominant epitopes are known to suppress a primary immune response to other antigenic determinants by a number of mechanisms. Many pathogens have used this strategy to subvert the immune response and may be a mechanism responsible for limited vaccine efficacies. HIV-1 vaccine efficacy appears to be complicated similarly by a limited, immunodominant, isolate-restricted immune response generally directed toward determinants in the third variable domain (V3) of the major envelope glycoprotein, gp120. To overcome this problem, we have investigated an approach based on masking the V3 domain through addition of N-linked carbohydrate and reduction in net positive charge. N-linked modified gp120s were expressed by recombinant vaccinia virus and used to immunize guinea pigs by infection and protein boosting. This modification resulted in variable site-specific glycosylation and antigenic dampening, without loss of gp120/CD4 binding or virus neutralization. Most importantly, V3 epitope dampening shifted the dominant type-specific neutralizing Ab response away from V3 to an epitope in the first variable domain (V1) of gp120. Interestingly, in the presence of V3 dampening V1 changes from an immunodominant non-neutralizing epitope to a primary neutralizing epitope with broader neutralizing properties. In addition, Ab responses were also observed to conserved domains in C1 and C5. These results suggest that selective epitope dampening can lead to qualitative shifts in the immune response resulting in second order neutralizing responses that may prove useful in the fine manipulation of the immune response and in the development of more broadly protective vaccines and therapeutic strategies.

AIDS Vaccines↗
PubMed1992

Human immunodeficiency virus type 1 clones chimeric for the envelope V3 domain differ in syncytium formation and replication capacity.

Chimeric human immunodeficiency virus type 1 (HIV-1) molecular clones differing only in the envelope V3 region were constructed. The V3 regions were derived from two HIV-1 isolates with a non-syncytium-inducing, non-T-cell-tropic phenotype and from four HIV-1 isolates with a syncytium-inducing, T-cell-tropic phenotype. When assayed in SupT1 cells, the two chimeric viruses with a V3 region derived from the non-syncytium-inducing isolates did not induce syncytia and showed a low level of replication. The four chimeric viruses with a V3 region derived from the syncytium-inducing isolates did induce syncytia and replicated efficiently in SupT1 cells. In A3.01 cells, which do not support syncytium formation, the V3 loop affected replication similarly. Upon prolonged culture in SupT1 cells, the phenotype of a non-syncytium-inducing, low-replicating chimeric HIV-1 converted into a syncytium-inducing, high-replicating phenotype. Mutations within the usually conserved GPGR tip of the loop, which were shown to be responsible for the conversion into the syncytium-inducing, high-replicating phenotype, had occurred. In vitro mutagenesis showed that coupled changes of amino acids at both sides of the tip of the V3 loop were able to convert the viral phenotype from non-syncytium-inducing, low replicating into syncytium inducing, high replicating. Our data show that the V3 loop is involved in both syncytium forming and replicative capacity of HIV-1.

Amino Acid Sequence↗
PubMed1992

Evolution of the V3 envelope domain in proviral sequences and isolates of human immunodeficiency virus type 1 during transition of the viral biological phenotype.

The third variable domain (V3) of the envelope gene of human immunodeficiency virus type 1 contains a major neutralization epitope and determinants of syncytium-inducing (SI) capacity and replication rate (reviewed by J. P. Moore and P. L. Nara, AIDS Suppl. 2:S21-S33, 1991). Sequences were generated from DNA of samples taken 3 months apart over a period of 24 and 30 months from peripheral blood mononuclear cells (PBMC) of two individuals, both before and after cocultivation with uninfected donor PBMC. The isolated virus shifted from the non-syncytium-inducing (NSI) phenotype to the SI phenotype during the study period. This shift was associated with distinct changes in the V3 domain in both patients. The association of the phenotype shift with the V3 sequence changes was confirmed by construction of viruses with chimeric V3 loops. The shift from NSI- to SI-associated V3 variants was also seen in the uncultured PBMC of both patients, but not until 3 and 9 months after the detection of SI virus in culture. In the samples of uncultured PBMC DNA, several subgroups of sequences were found, indicating that the process of evolution may not be gradual and that several distinct populations can coexist. The paucity of intermediate sequences indicated that strong selection pressure was exerted on this part of the envelope. The early emergence of disease-associated SI variants in cultured material indicates that virus culture may have relevance for the in vivo situation.

Amino Acid Sequence↗
PubMed1991

Immunodominance and antigenic variation of the principal neutralization domain of HIV-1.

The principal neutralization domain (PND) of HIV-1 is located in the third variable region (V3) of the envelope glycoprotein gp 120. Cross-reactivity of experimental and natural sera with recombinant proteins containing the V3 region of four HIV-1 variants showed that a group of viruses (among which HIV-1 MN) had antigenically similar V3 regions. The V3 regions of HIV-1 IIIB and HIV-1 RF were antigenically distinct. Antibodies raised to V3 domains of two isolates from the "MN group" neutralized HIV-1 MN (and not HIV-1 IIIB), thus confirming the antigenic similarity of V3 of these isolates to that of HIV-1 MN. Human antibodies to the V3 region were shown to be mainly directed to the central area in V3, where the neutralization domain is. In addition, antibody reactivities in sera of 397 Dutch and 39 Tanzanian HIV-1-infected individuals show that the V3 neutralization domain is highly antigenic, and that viruses from the MN group predominate in The Netherlands and to a lesser extent in Tanzania. Thus, if the protective value of antibodies to the PND can be established, then PND (poly)peptides derived from the MN group may be important components of a subunit vaccine against HIV-1.

Amino Acid Sequence↗
PubMed1990

Evolution of sequences encoding the principal neutralization epitope of human immunodeficiency virus 1 is host dependent, rapid, and continuous.

The principal neutralization epitope of human immunodeficiency virus 1 is localized in the third variable (V3) domain of the external envelope and has been shown to bind isolate-specific antibodies. Therefore, the extent of variation within the nucleic acid sequence encoding this epitope was studied in DNA directly obtained from peripheral blood mononuclear cells of six children and their plasma donor. This revealed that the quasi-species distribution of sequences obtained after cloning varied from recipient to recipient and that the distance from the donor sequences increased over time. V3 nucleotide evolution rates averaged 9.5 x 10(-3) per site per year for silent sites and 11.4 x 10(-3) per site per year for nonsilent sites (vs. 9.7 and 9.8 x 10(-3) per site per year for a control region 5' adjacent to the V3 region) and, although individual differences were observed, did not correlate with the serum antigen levels or disease progression. Sequences of both the epitope coding region itself (V3) and the control region upstream diverted more from the donor sequence among children not progressing to AIDS than among children progressing to AIDS. The evolution of V3 sequences is apparently host dependent, rapid, and independent of the level of antigen expression.

Acquired Immunodeficiency Syndrome↗