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K Fransen

Publications and source records attributed to K Fransen.

At least 55 records · Page 3Linked to original sources
PubMed1996

Epidemiological and molecular characteristics of HIV infection in Gabon, 1986-1994.

OBJECTIVE: To describe trends in the prevalence of HIV-1 infection in different populations in Gabon, and the molecular characteristics of circulating HIV strains. METHODS: Data were collected on HIV prevalence through sentinel surveillance surveys in different populations in Libreville (the capital) and in Franceville. In Libreville, a total of 7082 individuals (hospitalized patients, tuberculosis patients, pregnant women, asymptomatic adults, prisoners) were recruited between 1986 and 1994. In Franceville, we tested 771 pregnant women and 886 healthy asymptomatic adults (1986-1988). Sera were screened for HIV antibodies by enzyme-linked immunosorbent assay (ELISA) and confirmed by Western blot or line immunoassay (LIA). Reactive samples in ELISA were tested for the presence of antibodies to HIV-1 group O viruses by ELISA using V3 peptides from HIV-1 ANT-70 and HIV-1 MVP-5180 followed by confirmation by LIA and a specific Western blot. Seventeen HIV-1 strains were isolated (1988-1993) and a 900 base-pair fragment encoding the env region containing V3, V4, V5 and beginning of gp41 was sequenced and a phylogenetic tree was constructed. RESULTS: HIV prevalence was relatively low and remained stable (0.7-1.6% in pregnant women, 2.1-2.2% in the general population). The prevalence was also stable among prisoners (2.1-2.6%). Among hospitalized and tuberculosis patients prevalence was higher and increased (1.8-12.7% and 1.5-16.2%, respectively). Only three sera had antibodies to HIV-1 group O. The 17 HIV-1 strains represent six different genetic subtypes including type O. CONCLUSION: Our data from 1986 to 1994 show a stable and low HIV prevalence in Gabon, and a high genetic diversity of HIV-1 strains. This, also observed in Cameroon, is in contrast to that found elsewhere in Africa. Differences in rate of spread of HIV infection are probably explained by interplay between numerous factors. The role of different HIV subtypes in the dynamics of the HIV epidemic should be examined further.

Adult↗
PubMed1996

Phylogenetic analysis of the env gene of HIV-1 isolates taking into account individual nucleotide substitution rates.

OBJECTIVE: To estimate the relative substitution rate of the individual positions in an alignment of HIV-1 env sequences coding for areas V3, V4, V5, and the beginning of gp41, and to study phylogenetic relationships between HIV-1 strains taking into account these substitution rate estimates. DESIGN: Phylogenetic comparison of 145 HIV-1 strains classified in HIV-1 group M, subtypes A-H and isolated from patients of 24 different geographical origins. METHODS: A new method recently developed for measuring the substitution rates of the individual nucleotides in a sequence alignment was applied to an alignment of env gene sequences. From the resulting substitution rate distribution, an equation was derived that describes the relationship between dissimilarity and evolutionary distance better than equations previously available. Phylogenetic trees were then constructed from matrices of distances computed using this new equation. RESULTS: 'Substitution rate calibration' offers detailed information on the relative substitution rate or variability of the nucleotides in the env gene. A large phylogenetic tree of 145 env gene sequences constructed by neighbour-joining and taking into account the substitution rate spectrum for this gene, clearly shows the existence of the eight subtypes A-H, all supported at a bootstrap level of 90% or higher. Intersubtype distances were between 0.25 and 0.38, which is considerably higher than those found in trees not considering differences in substitution rates among different alignment positions. CONCLUSIONS: Evolutionary distances are seriously underestimated when individual substitution rates are not considered in the estimation evolutionary distances. Furthermore, due to the more accurate estimation of evolutionary distances, naturally occurring HIV-1 intersubtype recombinants could be recognized more easily.

Base Sequence↗
PubMed1996

Multivariate analysis of human immunodeficiency virus type 1 neutralization data.

We report on the use of spectral map analysis of the inter- and intraclade neutralization data of 14 sera of human immunodeficiency virus type 1 (HIV-1)-infected individuals and 16 primary isolates, representing genetic clades A to H in group M and group O. This multivariate analysis has been used previously to study the interaction between drugs and receptors and between viruses and antiviral compounds. The analysis reveals the existence of neutralization clusters, not correlated with the known genetic clades. The structural factors that have been identified may correlate with the most important neutralization epitopes. Three key primary HIV-1 isolates, which allow discrimination of sera that are likely or unlikely to neutralize primary isolates from most of the genetic clades, were identified. Our method of analysis will facilitate the evaluation as well as the design of suitable HIV-1 vaccines, which induce high-titer interclade cross-neutralizing antibodies.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Virologic and serologic characteristics of a natural chimpanzee lentivirus infection.

This study set out to characterize the unique features of natural lentivirus infection in chimpanzees over time. The virologic and serologic characteristics of this infection were followed longitudinally in a naturally infected chimpanzee together with a small cohort of experimentally HIV-1-infected chimpanzees. The subsequent isolates from the naturally infected chimpanzee were all non-syncytium forming (NSI) versus syncytium forming in the experimentally infected animals. In contrast to HIV-1-infected chimpanzees virus load was higher and plasma viremia occurred but in a cyclic pattern. Serologic follow-up suggested the development of neutralizing antibodies with subsequent escape of new isolates. Interestingly, the sequence of the principal neutralizing (V3 loop) domain (of HIV-1) remained constant over time. Antibodies to peptides from the V3 loop were type specific. The occurrence of persistent, fluctuating plasma viremia and NSI-type virus variants of this natural lentivirus infection are unique characteristics not previously reported in experimentally infected chimpanzees.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Biological phenotypes of HIV-1 subtypes A and B strains of diverse origins.

The identification of specific biologic phenotypic traits that can be correlated with different HIV-1 genetic subtypes was sought. The genetic subtypes were determined by either sequencing (Cameroonian strains, n = 18) or by the heteroduplex mobility assay (HMA) (Belgian strains, n = 21 and Ivorian strains, n = 25). Seventeen (81%) of the 21 Belgian isolates belonged to subtype B and 4 (17%) were subtype A strains. Subtype A variants were predominant in the two African countries studied; 11 (61%) of 18 strains from Cameroon and 23 (92%) of 25 strains from the Ivory Coast. Of the 64 isolates, 38 (58%) and 19 (29%) belonged to subtypes A and B, respectively. No significant difference was observed for biological phenotypes (slow/low and rapid/high) of both genetic subtypes. In symptomatic individuals, however, a significantly higher number of subtype B isolates were of rapid/high phenotype, compared with subtype A (5 of 10; 50%) vs. 2 of 22; 9%), respectively; X2 = 6.7, P = 0.02). The findings suggest that overall HIV-1 isolates belonging to genetic subtype B are not distinguishable from subtype A variants on the basis of their biological phenotypes. Syncytium-inducing variants were less prevalent regardless of the geographic origin of the isolates.

Base Sequence↗
PubMed1995

Risk factors for mother-to-child transmission of human immunodeficiency virus-1 infection.

OBJECTIVE: Our aim was to examine maternal, obstetric, and infant characteristics of mother-to-child transmission of human immunodeficiency virus-1 in Nairobi, Kenya. STUDY DESIGN: Proviral human immunodeficiency virus-1 was detected by polymerase chain reaction in peripheral blood samples taken between 6 weeks and 3 months of age from 107 children born to human immunodeficiency virus-1 seropositive women. The association of maternal, infant, and obstetric variables with human immunodeficiency virus-1 transmission was examined. RESULTS: The mother-to-child transmission rate was 31% (95% confidence interval 21.6 to 40.2) as defined by the presence of proviral human immunodeficiency virus-1 in the infant. Variables associated with transmission in a univariate analysis included placental inflammation (7/12 in the transmitting group as compared with 2/22 in nontransmitters, p = 0.006), low maternal CD4 and high CD8 percentages (21% and 52%, respectively, in transmitting mothers and 32% and 40% in nontransmitting mothers; p = 0.001), and the gender of the neonate (20/29 infected neonates were female as compared with 26/65 noninfected children, p = 0.02). Sexually transmitted diseases were found more often in transmitting mothers but the differences were not significant. Birth weight and gestational age were not related to vertical transmission of human immunodeficiency virus-1. CONCLUSION: Risk factors for mother-to-child transmission of human immunodeficiency virus-1 included chorioamnionitis, an impaired maternal immune status, and female gender.

Adult↗
PubMed1995

Standardisation of primers and an algorithm for HIV-1 diagnostic PCR evaluated in patients harbouring strains of diverse geographical origin. The Belgian AIDS Reference Laboratories.

Eight Belgian AIDS Reference Laboratories established a multicentre quality control to evaluate the performance of their diagnostic human immunodeficiency virus type 1 (HIV-1) DNA polymerase chain reaction (PCR). A set of Belgian and African HIV-1 seropositive and seronegative patient samples, collected in Belgium, and the British Medical Research Council (MRC) HIV-1 PCR reference reagent kit, containing plasmid HIV-1 DNA at several dilutions in human carrier DNA with appropriate negative controls, were tested by the laboratories. No false positive results were reported. All laboratories were able to detect one to two copies of HIV-1 DNA. Among the 17 Belgian and African HIV-1 seropositives, some laboratories reported up to four indeterminate results, mainly due to failure of the SK38-39, SK68-69 (Ou et al. (1988) Science 239, 295-297) and/or gag881-882 (Simmonds et al. (1990) J. Virol. 64, 864-872) primers and a poorly performing algorithm. Only the H1POL4235-4538 nested pol primer set, developed by one of the laboratories, correctly identified all the tested HIV-1 positive and negative samples. Consequently, the laboratories decided to evaluate these pol primers as a reference primer set and to standardise the testing algorithm. All laboratories achieved a sensitivity and specificity of 100% on testing 10 additional Belgian and African patient samples, when adapting a standardised algorithm based on three HIV-1 primer sets, one of which is the H1POL4235-4538 primer set.

Africa↗
PubMed1995

Detection of HIV-1 RNA in plasma and serum samples using the NASBA amplification system compared to RNA-PCR.

The presence of HIV-1 RNA in the plasma and serum of European and African patients was monitored using RNA-polymerase chain reaction (RNA-PCR) and the new isothermal NASBA nucleic acid amplification system encompassing a gel-based detection assay (ELGA). Identical RNA extraction procedures, provided by the NASBA amplification system, were used for both methods. The detection limit for HIV-1 RNA, measured on a 10-fold dilution series of spiked HIVIIIB in negative plasma, was about 0.05 CCID50 per test for both methods. Both NASBA and RNA-PCR were more sensitive than a p24 assay for the detection of circulating HIV-1 virus in blood: 17 of the 34 (50%) p24 antigen-tested seropositives were p24-positive while 32 (94%) were positive by NASBA and 30 (88%) by RNA-PCR. Among the 45 seropositives, 34 of which were tested for p24 antigen, 43 (96%) were positive by NASBA and 41 (91%) by RNA-PCR. Almost all seropositives had a detectable viral load in 100 microliters plasma. Lower viral loads were only encountered in some healthy seropositives with a higher CD4 count. There was no cross-reactivity with HIV-2 or HIV-I with both the RNA-PCR and NASBA. The extraction method used permitted the detection of HIV-1 RNA equally well in serum and in plasma with heparin or EDTA.

Africa↗
PubMed1995

Evaluation and comparison of the Amplicor HIV-1 PCR kit with an 'in-house' nested PCR.

BACKGROUND: The polymerase chain reaction (PCR), a powerful gene amplification technique, is moving rapidly from the research laboratory into routine clinical use. OBJECTIVES: To evaluate the specificity and sensitivity of a commercially available PCR kit, the Amplicor HIV-1 PCR kit (AMP) and to compare it with an in-house nested PCR, which amplified part of the POL gene (POL(n)). STUDY DESIGN: A total of 517 samples were tested by AMP, including 159 fresh whole blood specimens from HIV-1 antibody positive Europeans and 358 archival samples (338 seropositive and 20 seronegative individuals) originating from 35 different countries in Africa and Europe. We compared the performance of AMP on the archival samples with POL(n). RESULTS: The overall sensitivity and specificity as compared to HIV-1 serology were 93% and 100%, and 96% and 100%, for AMP and the in-house PCR, respectively. Repeat testing on co-cultured lymphocytes increased the sensitivity of AMP to 95%. CONCLUSIONS: AMP is a rapid, and easy to use commercially available PCR kit, since only one amplification of the test sample is required. Moreover, the use of radioactivity is omitted, and reading of the test can be done with a spectrophotometer. The use of at least one additional primer pair may increase confidence in distinguishing a positive and negative sample by both PCR techniques.

Journal Article↗
PubMed1995

Correlation between genetic and biological properties of biologically cloned HIV type 1 viruses representing subtypes A, B, and D.

The relationship between the genetic variability in the V3 loop and the biological characteristics of 38 biological clones from 5 European and 7 African HIV-1 isolates belonging to 3 different subtypes (subtype A, B, and D) was investigated. Seventeen of 19 clones displaying a syncytium-inducing (SI) capacity had a positively charged amino acid located at position 11 and/or 25 in the V3 loop sequence. All 19 non-syncytium-inducing (NSI) virus clones lacked such a positive charge at the same positions (p < 0.001). The mean of net charge in the overall V3 loop sequences of the SI clones was higher than that of the NSI clones (p < 0.001). Within the same strains, the SI clones replicated faster/higher than the NSI clones in peripheral blood mononuclear cells (p < 0.01), but not in CD4+ T cell cultures (p > 0.1). All SI clones but only 5 of 19 NSI clones could replicate in human continuous T cell and monocytic cell lines (p < 0.001). A higher number of positively charged amino acid substitutions was found among the subtype D SI clones. Only one of eight autologous sera tested had the ability to neutralize the contemporaneously isolated NSI clones, but not the SI clones. This study indicates that the V3 loop amino acid sequences of HIV-1 biological clones from different origins belonging to different genetic subtypes are clearly correlated with viral syncytium-inducing capacity, cell tropism, and replication rate.

Amino Acid Sequence↗
PubMed1995

Reduced capacity of antibodies from patients infected with human immunodeficiency virus type 1 (HIV-1) group O to neutralize primary isolates of HIV-1 group M viruses.

Neutralizing antibody patterns in sera of persons infected with human immunodeficiency virus type 1 (HIV-1) groups M and O to their homologous and heterologous primary isolates were determined in a peripheral blood mononuclear cell-based neutralization assay and correlated with their ability to bind to V3 loop synthetic peptides. Most HIV-1 group M sera (9/16) neutralized HIV-1 group O viruses, whereas fewer group O sera (3/13) only weakly neutralized HIV-1 group M viruses. Group M sera neutralizing HIV-1 group O viruses neutralized other HIV-1 group M viruses with titers of 1:10-1:1280. V3 loop binding capacity of sera did not reflect their neutralizing capacity of the homologous isolate. Despite the reduced neutralizing capacity of group O-infected patients' sera to group M viruses, some group M-infected patients' sera neutralized both HIV-1 group M and O isolates, suggesting that they share some conserved neutralizing epitopes.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Design and evaluation of new, highly sensitive and specific primers for polymerase chain reaction detection of HIV-1 infected primary lymphocytes.

Primer pairs in the HIV-1 POL and ENV genes were evaluated by performing a PCR on lysed peripheral blood mononuclear cells (PBMCs) from 96 HIV-1 seropositive and 40 seronegative individuals originating from 16 different geographical localities in Africa, Europe and Haiti. A single PCR using primer pairs to the LTR, GAG and ENV regions and detection by radioactively labelled oligonucleotide probes was compared to a nested PCR scheme using newly designed POL and ENV primers which used ethidium-bromide staining of the amplified product on agarose gel. The newly designed POL nested primer pair was shown to be highly sensitive (93%) and specific (100%) for the detection of HIV-1 proviral DNA of very diverse geographical and genetic origin, including highly aberrant HIV-1 isolates. The sensitivity of the newly designed ENV primers was 68.7%, which does not differ significantly from the sensitivity of the classical primers, SK 68/69. Both ENV primers were unable to amplify two SIVcpz isolates from naturally infected chimpanzees.

Africa↗
PubMed1994

Effect of methodology on detection of HIV-1/HIV-2 dual infections in Côte d'Ivoire.

Dual seroreactivity to the human immunodeficiency virus (HIV) types 1 and 2 is common in Côte d'Ivoire. To assess whether dual infection is the reason for dual seroreactivity, different methods for detection of HIV-1 and HIV-2 viruses were compared. PCR on primary uncultured lymphocytes of 56 dually seropositive samples revealed the presence of both HIV-1 and HIV-2 proviral DNA in 23 (41%) cases. In 7 other dual seropositive persons, PCR was carried out on the primary lymphocytes as well as on lymphocytes after 3 and 6 weeks of cocultivation. More cultures, 5/7 (71%), were positive for both viruses at 3 weeks compared to 0/7 at 6 weeks post cultivation. Moreover, 2 out of 3 samples, where only HIV-1 was detected in uncultured cells, were positive for both viruses after 3 weeks of cultivation. These data indicate that the sensitivity of HIV-2 detection can be increased by stimulation of patients' lymphocytes. A higher number of dual seropositive individuals (10/23 (48%)) had antibodies able to neutralize simultaneously both HIV-1 and HIV-2 prototype viruses than did HIV-1 antibody-positive sera (5/21 (24%)) or HIV-2 antibody positive sera (3/18 (17%)). The prevalence of dual seropositives being infected with both viruses is highly dependent on the method used to detect infection. There is a need to standardize virological markers in order to gain a better insight into the relative proportions of HIV-1, HIV-2 and HIV-1/HIV-2 dually infected persons.

Antibody Specificity↗
PubMed1994

Genetic and antigenic variability of HIV type 1 in Brazil.

Six Brazilian strains of human immunodeficiency virus type 1 (HIV-1) were isolated from infected individuals residing in different regions of Brazil between 1987 and 1989. Phylogenetic analysis based on an 860-base pair env fragment, including V3, V4, V5, and the beginning of gp41, classified the Brazilian strains significantly in genotype B, with interhost distances between 5.9 and 13.1% (mean value, 10%). Amino acid sequence analysis of the V3 loop revealed that three strains contained the North American/European GPGR motif as the tip of the loop whereas in the other three strains proline (P) was substituted by tryptophan (W), methionine (M), or phenylalanine (F). A consensus peptide, Bra-cons, was designed containing GWGR as the tip of the loop. Serological reactivity to the Bra-cons peptide and other V3 peptides (MN, SF2, HBX2, RF, MAL, ELI, Z6, and a Côte d'Ivoire peptide, CI-cons) was compared for 114 HIV-1-positive sera from Rio de Janeiro. Sixty-nine sera (60.5%) reacted with peptides belonging to genotype B, of which 10 sera also reacted with peptides belonging to genotype A (n = 7) and D (n = 3). Eighteen sera (15.8%) had binding antibodies to the Bra-cons peptide. A high number of sera (n = 43; 37.7%) had no antibodies to any of the V3 peptides tested. This result suggests that HIV-1 variants with aberrant V3 loops may circulate in Rio de Janeiro.

Acquired Immunodeficiency Syndrome↗