PubMed Health⌕ Search

Biomedical subjects

L van der Hoek

Publications and source records attributed to L van der Hoek.

13 recordsLinked to original sources
PubMed2000

Slower decline of plasma HIV-1 RNA following highly suppressive antiretroviral therapy in primary compared with chronic infection.

OBJECTIVES: To study the effect of highly suppressive antiretroviral therapy on the slopes of HIV-1 RNA decline in primary compared with chronic HIV-1 infection. METHODS: Slopes of HIV-1 RNA decline in plasma were compared before and after the start of highly suppressive antiretroviral therapy from five acutely infected patients who started treatment 2 to 5 weeks following the onset of clinical symptoms. Slopes of decline after the initiation of therapy were also compared with those found in 12 chronically infected individuals on the same therapy. Numbers and percentages of activated CD4 and CD8 T cells at baseline were compared as well. RESULTS: The pre-treatment slopes of HIV-1 RNA decline in the acutely infected individuals increased significantly (P = 0.0001) after the start of anti-retroviral therapy. However, these post-treatment slopes were lower than those found in the chronically infected individuals (P= 0.012). Slopes were inversely correlated (P= 0.012) with baseline HIV-1 RNA. Although the number of CD38+HLA-DR+ CD4 cells was higher in primary infection (P= 0.02), the percentage did not differ between primary and chronic infection. CONCLUSIONS: These findings indicate that antiretroviral therapy contributes significantly to the clearance of HIV-1 during primary infection. Based on the mathematical model the less steep RNA slope following the start of treatment in primary infection can be predicted to be the result of lower clearance of productively infected cells and higher burst size per cell per unit time. This may indicate a growing immune response to HIV-1 in this very early stage of infection.

Acute Disease↗
PubMed1998

Human immunodeficiency virus type 1 in faeces and serum: evidence against independently evolving subpopulations.

It is not known whether independent tissue-specific evolution accounts for the differences between human immunodeficiency virus type 1 (HIV-1) subpopulations in intestinal tissue and blood. To study this, sequential serum samples from three persons were analysed for the presence of HIV-1 V3 genotypes which were detected exclusively in faeces at a specific time-point. For two persons the faeces genotype was found in serum samples collected before the time of faeces collection: 7 months for one person and 32 months for the other person. In the third person, serum collected 1 month after faeces collection contained the faeces genotype in abundance. These data indicate that a difference between intestinal tissue and blood HIV-1 subpopulations is not the result of complete compartmentalization and independent HIV-1 evolution in intestinal tissue, but that it reflects an unequal distribution of HIV-1 in different tissues.

Amino Acid Sequence↗
PubMed1998

Genetic differences between human immunodeficiency virus type 1 subpopulations in faeces and serum.

To study human immunodeficiency virus type 1 (HIV-1) compartmentalization between intestine and blood, paired faecal and serum samples were collected from 204 HIV-1-infected persons. Direct sequencing of the gp120 V3 region obtained from 33 persons showed that faecal and serum sequences could be nearly homologous (0.3% different) or very dissimilar (11.3% different). Individual clones were obtained and sequenced from the faecal and serum samples of 13 persons. In 6 persons the HIV-1 subpopulations in faeces and serum were similar, whereas in 7 persons, distribution of V3 genotypes showed a marked difference. Genetic characterization of the HIV-1 subpopulations showed less heterogeneity in faecal subpopulations than in serum subpopulations in 5 of the 7 subjects. Furthermore, faecal and serum subpopulations differed predominantly by nonsynonymous nucleotide substitutions (in 6 of 7 persons). Comparison of the HIV-1 subpopulations in faeces and serum of these 7 persons, using resampling techniques, revealed a significant difference between faecal and serum subpopulations at an N-linked glycosylation site, C-terminal of the V3 loop (amino acids 331-333). Sequences from faecal subpopulations of all 7 persons contained a glycosylation site at amino acid position 331-333. Four of these 7 harboured serum variants lacking a glycosylation site at this position. The faecal subpopulations in these 4 persons showed limited nonsynonymous substitutions compared to synonymous substitutions, indicating that purifying selection is operational on these subpopulations.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Prevalence of Campylobacter-associated diarrhea among patients infected with human immunodeficiency virus.

We performed a cross-sectional study at an outpatient AIDS clinic to assess the prevalence of Campylobacter species in stool specimens from 201 consecutive patients infected with human immunodeficiency virus (HIV). We characterized campylobacters phenotypically and genetically by using primers for the group of common species (i.e., C. jejuni, C. coli, C. lari, and C. upsaliensis) and for most individual uncommon species. We performed cultures with use of a membrane filter technique on nonselective blood agar and found that Campylobacter species were the most frequent enteropathogenic bacteria: the organisms were recovered from 7 (16%) of 43 patients with diarrhea and 5 (3%) of 158 patients without diarrhea (P = .001). We isolated only one campylobacter with use of conventional culture techniques on selective media. Phenotypic characterization of 10 campylobacter strains resulted in the misidentification of four isolates. C. upsaliensis was the most frequently isolated species, followed by C. jejuni and C. coli. Two strains could not be identified with the available primers. Two of 12 Campylobacter strains were resistant to erythromycin, and two were resistant to ciprofloxacin. We conclude that Campylobacter species other than C. jejuni can frequently be detected in the stools of HIV-infected patients and that these organisms could be associated with diarrhea.

Adult↗
PubMed1996

Human immunodeficiency virus type 1 RNA populations in faeces with higher homology to intestinal populations than to blood populations.

To determine whether human immunodeficiency virus type 1 (HIV-1) in faeces is representative of the HIV-1 population in intestinal tissue, we studied HIV-1 V3 variation in faeces, intestinal biopsies and serum from two individuals. Phylogenic analysis of HIV-1 V3-coding RNA in faeces from one individual showed three distinct genotypes. Viruses belonging to all three genotypes were also present in sigmoidal tissue and in serum. Jejunal tissue contained two of these three genotypes. Analysis of the V3-coding RNA in faeces of the other individual showed five distinct genotypes. One of these genotypes was present in all specimens from this individual. Besides this shared genotype, jejunal tissue and serum contained sequences belonging to one other genotype. In addition, one of the other three V3 variants was detected in sigmoidal tissue. For both persons the shared HIV-1 RNA genotypes in faeces and serum displayed a distinctly different frequency distribution. In one individual, the genotype which was detected in a majority of the clones in faeces (59%) and as a minority in serum (11%), was the most abundant genotype in jejunal and sigmoidal tissue (61% and 80%, respectively). For the other individual the genotype that was present in faeces in a significant number of clones (43%) was detected in serum as a minority (8%), whereas this genotype composed 47% of the clones isolated from jejunal tissue. Taken together these data suggest that faeces contain HIV-1 sequences that are derived from local HIV-1 replication in intestinal tissue.

Amino Acid Sequence↗
PubMed1995

Isolation of human immunodeficiency virus type 1 (HIV-1) RNA from feces by a simple method and difference between HIV-1 subpopulations in feces and serum.

A simple method for the isolation and subsequent detection of human immunodeficiency virus type 1 (HIV-1) RNA from feces is described. Viral RNA was isolated by the method developed by Boom et al. (R. Boom, C.J.A. Sol, M.M.M. Salimans, C.L. Jansen, P.M.E. Wertheim-van Dillen, and J. van der Noordaa, J. Clin. Microbiol. 28:495-503, 1990), which was adapted for feces. HIV-1 RNA was detected by reverse transcription (RT) followed by a nested PCR encompassing the V3 region. Reconstruction experiments revealed that the efficiencies of the extraction technique and the subsequent RT-PCR were not considerably affected by the varied composition of feces. The method was applied on fecal specimens from 18 HIV-1-infected individuals, among which were samples that had been stored for 9 years. It appeared that HIV-1 RNA was detectable in the feces of 12 persons (67%). Viral RNA was present in the feces of persons who fulfilled the criteria for CDC class II and CDC class III HIV infection as well as in patients who were diagnosed with AIDS (CDC class IV). Direct sequencing of amplimers obtained from paired fecal and serum specimens showed that differences in sequence heterogeneity existed. In one patient a remarkable difference in the HIV-1 sequences between isolates from feces and serum was observed. In conclusion, HIV-1 RNA is frequently present in the feces of HIV-1-infected individuals, and in some cases the HIV-1 subpopulation in feces differs from the HIV-1 subpopulation in serum.

Amino Acid Sequence↗
PubMed1995

Syncytium-inducing (SI) phenotype suppression at seroconversion after intramuscular inoculation of a non-syncytium-inducing/SI phenotypically mixed human immunodeficiency virus population.

Two distinct biological phenotypes of human immunodeficiency virus (HIV) have been described: the non-syncytium-inducing (NSI) phenotype, best characterized by the inability to infect MT-2 cells, and the syncytium-inducing (SI) phenotype, with the ability to infect MT-2 cells. The earliest virus population observed following HIV transmission is generally of the NSI phenotype, even after exposure to inocula of mixed NSI/SI phenotype. In this study, the issue of intrapatient selection of virus phenotype following transmission was addressed by studying two cases of accidental transmission. A comparison of the sequences of the V1-V2 and the V3 coding regions of the envelope gene and the p17 region of the gag gene showed that the donor-recipient pairs were tightly clustered in all gene segments, but away from local and published transmission controls. The intrasample variation of the p17 sequence was greater in the recipients and smaller in the donors than that of the V3 region sequence, indicating selection of V3 at transmission. In these transmission cases, the effects of an intravenous inoculation of a small quantity of blood containing predominantly SI V3 sequences (6 of 8 clonal sequences) were compared with those of an intramuscular inoculation of a large quantity of blood containing predominantly NSI viruses (14 of 16 clonal sequences). Both SI and NSI V3 regions were demonstrated to be phenotypic expressions of genetically related viral strains. The inoculation of the predominantly SI virus population resulted in the persistence of an SI virus population in the recipient and a rapid CD4+ T-cell decline. The inoculation of the predominantly NSI population resulted in a selective amplification of SI viruses before seroconversion, followed by a suppression of SI viruses at seroconversion and a rapid decline of CD4+ T-cell numbers. These data suggest that the suppression of SI viruses can be accomplished following the development of HIV-specific immunity and that the ability to suppress SI viruses does not prevent the development of immunodeficiency.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Antibody responses to HIV-1 envelope and gag epitopes in HIV-1 seroconverters with rapid versus slow disease progression.

We studied the relationship between the rate of disease progression after HIV-1 seroconversion and the level of IgG antibody response to HIV-1 envelope and core epitopes. This was done by comparing a group of fast-progressing individuals and a group of slow-progressing individuals for serum IgG titers to peptides from the gp120-V3 neutralization domain, to a peptide from the immunodominant gp41 epitope (residues 590 to 607), and to recombinant gp120 and p24. The two groups displayed a large overlap in titers to the envelope epitopes, which precluded their differentiation at most time points after seroconversion. Low responsiveness to envelope antigens was not only found in a few fast-progressors but also in one individual who remained asymptomatic for at least 92 months after seroconversion. The only significant differences between the groups were found in the first months after seroconversion when the responses to the V3 domain and the gp41 epitope were more vigorous in the group of fast-progressors. Furthermore, on evaluating ratios of anti-V3 antibody titers to anti-gp120 antibody titers we found no indication that fast disease progression was associated with a restriction in antibody response to the V3 epitope. We did confirm the finding that fast disease progression is associated with low levels of p24-directed antibodies, both early after seroconversion and at later stages. These data demonstrate that levels of IgG antibodies to envelope epitopes are poor predictors of rapid disease progression and suggest that the role of V3-directed neutralizing antibodies in preventing subversion of the immune system is not decisive in natural HIV-1 infection.

Adult↗
PubMed1994

Frequent and early HIV-1MN neutralizing capacity in sera from Dutch HIV-1 seroconverters is related to antibody reactivity to peptides from the gp120 V3 domain.

The temporal development of HIV-1 neutralizing activity and antibodies to the gp120-V3 neutralization domain were studied in sera from 20 Dutch HIV-1-infected individuals followed from seroconversion on. Serum neutralizing capacity was assessed with three T cell line-tropic isolates: HIV-1MN, HIV-1HXB2, and the patient isolate HIV-1(320). Neutralizing activity to HIV-1MN developed in 18 individuals (90%) within 0 to 10 months after seroconversion. Parallel evolution of IgG reactivity to V3 peptides of United States/European type variants, and the capability of such peptides to completely inhibit HIV-1MN neutralization in four of five tested sera (taken 1-2 years after seroconversion), indicate that a large proportion of HIV-1MN neutralizing antibodies is directed to V3. The early appearance and high frequency of HIV-1MN neutralizing activity in the Dutch study group indicate the close relationship of HIV-1MN to HIV-1 variants circulating in the Netherlands. Neutralizing activity to HIV-1HXB2 (in 15 of 20 individuals) developed several months after that to HIV-1MN in all individuals (average, 10 months after seroconversion) and was not seen in the absence of HIV-1MN neutralizing activity. Neutralizing activity to the Dutch isolate HIV-1(320) (found in 11 of 18 tested individuals) emerged simultaneously with that to HIV-1MN in 4 individuals but appeared later in 7. In most individuals, HIV-1HXB2 neutralization was not accompanied by reactivity to a V3 peptide from this strain, indicating that the extension of neutralizing activity to more divergent strains, which takes place at later stages, must be attributed to non-V3-directed antibodies.

Adult↗
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↗
PubMed1988

Human antibody response to a strain-specific HIV-1 gp120 epitope associated with cell fusion inhibition.

PEPSCAN analysis, performed using 536 overlapping nonapeptides derived from the HTLV-III B nucleotide sequence of the region encoding the external envelope protein of 120 kDa (gp120), identified in the V3 region of gp120 a major binding site for antibodies of HIV-1-infected humans. The minimal amino acid sequence of this antibody binding site was demonstrated by multiple length scanning to be five to eight amino acids in length: (G)PGRAF(VT), i.e. amino acids 312-319. A peptide (Neu 21) containing this binding site for human antibodies (KSIRIQRGPGRAFVTIG) was synthesized and shown to induce HTLV-III B cell fusion-inhibiting antibodies in rabbits and mice. Antibodies binding to this HTLV-III B/LAV-1-specific peptide were shown to be primarily of the IgG 1 subclass, appeared within 6 months after HIV-1 antibody seroconversion in six out of 14 men studied, and persisted throughout the follow-up period of 10-24 months. The other eight seroconverting men did not develop antibodies to Neu 21 during the observation period. The appearance of antibodies to Neu 21 paralleled the capacity of the serum to inhibit HTLV-III B in cell fusion. HIV-1-infected men with Kaposi's sarcoma exhibited a similar frequency of antibodies to the synthetic peptide Neu 21 (14 out of 39, 36%) as asymptomatic HIV-1-infected men (112 out of 319, 35%). Adults with Pneumocystis carinii pneumonia had a significantly lower frequency (11 out of 78, 14%) of antibodies to Neu 21. Similarly, a low prevalence of antibodies to Neu 21 (8 out of 43, 19%) was observed among symptomatic HIV-1-infected children.

Amino Acid Sequence↗