PubMed Health⌕ Search

Biomedical subjects

K Fransen

Publications and source records attributed to K Fransen.

At least 19 recordsLinked to original sources
PubMed2005

Pediatric human immunodeficiency virus screening in an African district hospital.

In order to evaluate alternative tests and strategies to simplify pediatric human immunodeficiency virus (HIV) screening at the district hospital level, a cross-sectional exploratory study was organized in the Democratic Republic of the Congo. Venous and capillary phlebotomies were performed on 941 Congolese children, aged 1 month to 12 years (153 children under 18 months and 788 children more than 18 months old). The HIV prevalence rate was 4.7%. An algorithm for children more than 18 months old, using serial rapid tests (Determine, InstantScreen, and Uni-Gold) performed on capillary blood stored in EDTA tubes, had a sensitivity of 100.0% (95% confidence interval [CI], 88.9 to 100.0%) and a specificity of 100.0% (95% CI, 99.5 to 100.0%). The results of this study suggest that the ultrasensitive p24 antigen assay may be performed on capillary plasma stored on filter paper (sensitivity and specificity, 100.0%; n=87) instead of venous plasma (sensitivity, 92.3%; specificity, 100.0%; n=150). The use of glucolets (instruments used to perform capillary phlebotomies), instead of syringes and needles, may reduce procedural pain and the risk of needle stick injuries at a comparable cost. Compared to the reference, HIV could have been correctly excluded based on one rapid test for at least 90% of these children. The results of this study point towards underutilized opportunities to simplify phlebotomy and pediatric HIV screening.

AIDS Serodiagnosis↗
PubMed2004

The role of non-viral load surrogate markers in HIV-positive patient monitoring during antiviral treatment.

Monitoring the efficacy of highly active antiretroviral treatment (HAART) is crucial if disease progression and the emergence of viral mutants are to be avoided. Classical viral load monitoring is too expensive for large-scale use in resource-limited settings. Three alternative measures, CD4 count, total lymphocyte count (TLC) and haemoglobin, were evaluated as surrogate markers of treatment success (viral load below detection level) among 710 HIV-positive patients who started HAART in an HIV treatment centre in Belgium. TLC correlated well with changes in CD4 counts during HAART, but an increase in TLC alone was a poor predictor of treatment success. A combination of increases in both haemoglobin levels and TLC proved a reliable predictor of successful treatment outcome comparable to the increase in CD4 count, but its specificity and sensitivity were low.

Adult↗
PubMed2004

Five-year immunological outcome of highly active antiretroviral treatment in a clinical setting: results from a single HIV treatment centre.

Our objective was to study the evolution of CD4 cell count five years after starting highly active antiretroviral treatment (HAART) in a clinical setting. The study was performed at the HIV outpatient clinic, Institute of Tropical Medicine, Antwerp. All patients (n = 225) who started HAART in 1997, who had a CD4 cell count within six months prior to starting HAART and who were subsequently followed for at least two years were included. Change in CD4 cell count after start of HAART and the influence of patient and clinical factors were investigated using graphical exploration, endpoint analysis and mixed-effects linear regression. The mean CD4 cell count at start of HAART was 280 cells/mm(3). At the five-year endpoint of the study the mean increase in CD4 cell count was 333 cells/mm(3), while 79% of the patients had a viral load less than 400 copies/mL. There was a significant negative correlation between increase in CD4 cell count at five years and time since first positive HIV test at start of HAART (P = 0.021). Patients who ever had a HAART interruption of more than seven days had a significantly lower increase in CD4 cell count than those who did not (225 cells/mm(3) compared with 438 cells/mm(3); P < 0.001). A mixed-effects linear regression model additionally suggested a significant impact of exposure to antiretrovirals prior to HAART (P = 0.03). Overall, the recovery of CD4 cell count after five years of HAART is good, although therapy interruptions have an important negative impact.

Adult↗
PubMed2002

Comparative evaluation of eight commercial enzyme linked immunosorbent assays and 14 simple assays for detection of antibodies to HIV.

To evaluate the performance of 22 assays for the detection of antibodies to HIV. Twenty-two assays for the combined detection of antibodies to HIV-1 and HIV-2, were evaluated on the same panel of serum specimens of diverse origin. Eight of the assays were ELISAs and the remaining 14 were simple, assays read visually. The specimen panel consisted of anti-HIV positive and negative samples from Africa (n=192), Europe (n=206), Asia (n=99) and Latin America (n=98). In addition to estimations of sensitivity and specificity, the assays were assessed, using a novel scoring system, for their ease of performance and for their suitability for use in small laboratories and clinics. The sensitivities of the assays in terms of seroconversion were assessed using series of specimens collected from nine individuals undergoing seroconversion. Eight ELISAs and eight of 14 simple assays had sensitivities and specificities of >99 and 95%, respectively. The results of these evaluations will be of assistance to those responsible for the selection of appropriate anti-HIV assays according to laboratory circumstances, the purpose of the testing and the population being tested.

Confidence Intervals↗
PubMed2001

Quantitative assay for group M (subtype A-H) and group O HIV-1 RNA detection in plasma.

A quantitative HIV-1 test is described based on a competitive RT-PCR assay combined with a sandwich hybridization as a detection system. The internal RNA standard (IS) was designed specifically to be competitive during the amplification and during the hybridization step. Sample viral load determination was carried out with one RT-PCR in the presence of 10(3) IS copies. The HIV-1 copy number was calculated by reference to an external standard curve performed on known and increasing amounts of the reference HIV-1 (Ref HIV-1) RNA co-amplified with a constant amount of the IS RNA. The assay had a linear range from 10(1) to 10(6) HIV-1 copies. HIV-1 strains belonging to the different subtypes from group M, but also group O, were all detected. Absolute quantification of purified HIV-1 RNA copies gave identical results as the AMPLICOR HIV-1 Monitor assay. The quantification of patient's samples was evaluated according to different criteria such as dynamic range, sensitivity, efficacy of material recovery, reproducibility and convenience of sample handling. The microplate format of the assay combined with the colorimetric detection provides a convenient tool and fulfills the requirement for routine molecular diagnostic laboratories.

HIV Infections↗
PubMed2001

Evaluation of four HIV antigen tests.

A direct comparison of different HIV antigen assays is very helpful in making an informed choice, not only for the testing laboratories but also for healthcare workers in the developing world who are looking for reliable and inexpensive tests/methods in the follow-up of their treated patients. As a follow-up to the study published previously [Fransen K., Martens G., Stynen D., Goris A., Nys P., Nkengasong J., Heyndrickx L., Janssens W., van der Groen G., 1997. J. Med. Virol. 53, 31--35] where only two tests have been compared, four different commercial methods for HIV antigen determination in plasma and supernatant of cell cultures have now been evaluated on a limited sample size (88): COULTER HIV-1 p24 Antigen Assay (Coulter), (Test 1) INNOTEST HIV Antigen mAb (Innogenetics) (Test 2), Genetic Systems HIV-1 Ag EIA (Sanofi-Pasteur(1)) (Test 3) and VIDAS HIV P24 II (bioMérieux) (Test 4). Of the four tests used in this study, Test 2 was by far the most sensitive test. In a population of 88 follow-up samples from 35 different patients representing all stages of infection, the test detected confirmed p24 antigen at least once in 85.7% (30/35) of these patients, versus Test 3 in 74.3% (26/35), Test 4 in 71.4% (25/35), and Test 1 in 48.6% (17/35) of the patients. Test 2 detected confirmed p24 antigen in 84.9% of the follow-up samples, followed by Test 4 (65.9%), Test 3 (64.8%) and Test 1 (39.8%). Finally, Test 2 also proved best for detecting genetically diverse isolates.

Evaluation Studies as Topic↗
PubMed2001

Longitudinal comparison of virus load parameters and CD8 T-cell suppressive capacity in two SIVcpz-infected chimpanzees.

In a longitudinal study we address the hypothesis that resis tance to disease progression in lentivirus-infected chimpanzees is related to potent non-cytotoxic suppression of virus replication. In a long-term follow-up, the viral suppressive capacity in two simian immunodeficiency virus (SIV)cpz-infected chimpanzees was correlated with two polymerase chain reaction (PCR)- and two culture-based virus load measurements. In both animals, quantitative virus isolation (QVI) tended to decline slowly, whereas in vitro virus suppression was sustained or increased over time. In general, plasma virus loads in SIVcpz-infected animals were maintained for extended periods of time. Based on current assays that measure virus suppressive capacity in peripheral blood, it was not possible to conclude that virus suppression played a major role in the maintenance of the disease-free state in lentivirus-infected chimpanzees.

Animals↗
PubMed2001

Prevalence of genotypic resistance among antiretroviral drug-naive HIV-1-infected patients in Belgium.

OBJECTIVES: To estimate the prevalence and the evolution over time (1995-1998) of genotypic resistance to antiviral drugs in antiretroviral drug-naive HIV-1-infected patients in Belgium. DESIGN: Belgian Aids Reference Laboratories provided retrospective samples and clinical data from antiretroviral drug-naive HIV-1-infected patients who visited the hospital for the first time in 1995 (n=45), 1997 (n=75) and 1998 (n=111). Genotypic resistance to the three available classes of drugs was monitored using the Line Probe Assay (Innogenetics, Gent, Belgium). Additionally, ARMS-151 was performed for scoring multinucleoside resistance. RESULTS: The prevalence of genotypic resistance at baseline to nucleoside analogue reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs) were each between 10% and 20% for 1995, 1997 and 1998 without an increasing trend over time. For NRTIs, resistance mutations were mainly related to zidovudine in 1995, whereas in 1997 and 1998 baseline resistance was scored for zidovudine, lamivudine or for both drugs simultaneously. No patients displayed the multi-nucleoside resistance Q151M mutation. Baseline resistance mutations to protease inhibitors (PIs) did not rise significantly: 4.4% in 1995, 8% in 1997 and 9.9% in 1998. When scoring any resistance-related mutation, 26.6% displayed genotypic baseline resistance in 1995, 26.6% in 1997 and 31.5% in 1998. DISCUSSION: The prevalence of genotypic baseline resistance to any drug, as scored with LiPA, in naive HIV-1 patients in Belgium is 29%, with baseline resistance mutations to one or several drugs from all available classes of antiviral drugs. The ability of LiPA to pick up minor variants could be an explanation for the higher overall prevalence we observe, when compared to recent estimates in other countries of 16.3% and 22%, which were based on sequencing methods. According to the European guidelines for resistance testing, resistance testing in Belgium before starting antiviral therapy should be considered.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Ritonavir/saquinavir plus one nucleoside reverse transcriptase inhibitor (NRTI) versus indinavir plus two NRTIs in protease inhibitor-naive HIV-1-infected adults (IRIS study).

OBJECTIVES: To compare the efficacy, tolerability and safety of a ritonavir 400 mg/saquinavir hard gel fomulation 400 mg twice daily versus an indinavir 800 mg once every 8 h containing first-line protease inhibitor (PI) treatment regimen. METHODS: Open, randomized, multicentre clinical trial. PI-naive patients received either ritonavir/saquinavir and one nucleoside reverse transcriptase inhibitor (NRTI) or indinavir and two NRTIs. Intention-to-treat (ITT) and on-treatment (OT) analyses were performed. RESULTS: The baseline characteristics of the study participants were similar in both arms, 67 patients (37%) were naive to antiretroviral treatment. The proportion of patients who achieved a plasma viral load below the level of detection of 400 copies/ml at week 48 was 43% (39/90) in the ritonavir/saquinavir arm and 63% (57/90) in the indinavir arm (P=0.005, I

Acquired Immunodeficiency Syndrome↗
PubMed2000

Natural residues versus antiretroviral drug-selected mutations in HIV type 1 group O reverse transcriptase and protease related to virological drug failure in vivo.

HIV-1 group O viruses were first recognized as a distinct subgroup of HIV-1 with the isolation and characterization in 1990 of a virus (ANT70) from a woman (individual A) and her spouse (individual B), both from Cameroon (De Leys R, et al.: J Virol 1990;64:1207-1216). During the 5-6 years before treatment, individual A remained asymptomatic, with viral RNA levels between 2.5 and 2.8 log10 copies/ml, as measured by a newly developed group O-specific quantitative NASBA-based RNA assay. Individual B developed mild clinical symptoms, with 3.1 to 3.6 log10 copies of viral RNA per milliliter. HIV-1 sequences obtained from both individuals showed pretreatment residues in protease that confer resistance to protease inhibitors in group M viruses (10I, 36I, and 71V). Individual A showed an initial response to AZT, but shortly after addition of ddC and saquinavir, the RNA levels returned to baseline, while subsequent treatment with d4T, 3TC, and indinavir reduced the RNA level to less than 50 copies/ml for the time of follow-up. Individual B showed no response to AZT or ddC monotherapy, and a change to d4T, 3TC, and indinavir had, in contrast to individual A, only a temporary effect. While a multitude of mutations in HIV-1 group O reverse transcriptase (RT) and protease appeared that are associated with drug resistance in group M viruses, the observed T215N mutation in RT and the V15I and V22A mutations in protease have not previously been described and may represent resistance-conferring mutations specific to group O viruses. These results indicate that treatment of HIV-1 group O-infected individuals with antiretroviral drug regimens that include protease inhibitors might lead to rapid selection for resistance-conferring mutations. This probably results from preexisting protease residues contributing to reduced sensitivity of group O viruses to protease inhibitors, as is observed in vitro.

Amino Acid Sequence↗
PubMed2000

Blinded, multicenter quality control study for the quantification of human immunodeficiency virus type 1 RNA in plasma by the Belgian AIDS reference laboratories.

OBJECTIVE: In order to evaluate the interlaboratory variation of HIV-1 RNA measurements in plasma, the Belgian AIDS reference laboratories organized a blinded multicenter quality control study. METHODS: Atest panel of coded spiked HIV-1 plasma samples reflecting the dynamic range of the assay was composed and distributed. The HIV-1 RNA concentration of these samples was determined by the eight Belgian AIDS reference laboratories by means of the Amplicor HIV-1 Monitor version 1.5 assay. RESULTS: Analysis of the results demonstrated that there was little interlaboratory variation for the high concentration range (4.0-5.7 log10 copies/mL), never exceeding 0.2 log10 copies/mL. However the standard deviation for the low concentration range (2.6-3.9 log10 copies/mL) reached up to 0.22 log10 copies/mL. CONCLUSIONS: Since interlaboratory variability never reached 0.5 log10 copies/mL and each of the laboratories was able to detect four-fold differences in plasma HIV-1 RNA levels, the Amplicor assay can be used in multicenter studies without a centralized analysis of samples. Furthermore, this well-characterized proficiency panel of spiked plasma samples could be used as a standard in the study of interassay comparisons.

Belgium↗
PubMed2000

The HIV-2 genotype and the HIV-1 syncytium-inducing phenotype are associated with a lower virus replication in dendritic cells.

During sexual transmission, HIV infects the mucosal dendritic cells and is transferred to CD4 T cells. Whether HIV variants of a particular genetic (sub)type or phenotype selectively infect dendritic cells (DC) or are preferentially transferred to T cells remains highly controversial. To avoid the cumbersome use of primary dendritic cells, in vitro dendritic cell models were generated from precursors, either hematopoietic progenitor cells (HPC) or monocytes (MO). Productive infection in the dendritic cells and transfer of the virus to T cells was assessed for a range of HIV variants. HPC-derived dendritic cells (HPC-DC) were more susceptible to HIV-1 than to HIV-2 isolates. The HIV-1 group O strains were more productive in HPC-DC than group M, but amongst the latter, no subtype-related difference was observed. Both non-syncytium-inducing (NSI) and SI HIV isolates and lab strains could productively infect HPC-DC, albeit with a different efficiency. Adding blocking antibodies confirmed that both CCR-5 and CXCR-4 co-receptors were functional. Biological HIV-1 clones of the NSI/R5 phenotype infected more readily HPC-DC than SI/X4 clones. MO-derived dendritic cells were, however, more exclusive in their preference for NSI/R5 clones. Some HIV variants, that did not grow readily in HPC-DC alone, could be rescued by adding resting or pre-activated T cells. The present data show that HIV-2 isolates and SI clones replicate less in model-DC, but no preference for a particular HIV-1 subtype was evident. Co-culture with T cells could "correct" a limited growth in dendritic cells. Clearly, both intrinsic dendritic cell susceptibility and enhancement by T cells are explained only partly by HIV genotype and phenotype. The in vitro dendritic cell models seem useful tools to further unravel interactions between HIV, DC, and T cells.

CCR5 Receptor Antagonists↗
PubMed1999

Intrapatient variability of HIV type 1 group O ANT70 during a 10-year follow-up.

HIV-1 ANT70 is the first HIV-1 group O virus isolate obtained from a 25-year-old Cameroonian woman, who seroconverted in March 1987. This individual has remained asymptomatic and clinically healthy (clinical stage WHO 1, CDC II) even though she did not receive any antiretroviral therapy for HIV-1 before 97 months post-seroconversion. CD4+ T cell counts declined steadily to 200/microl at 70 months postseroconversion. The HIV-1 ANT70 nucleotide and amino acid sequence diversity of the V3C3-encoding env fragment within this individual was followed over a 10-year period. RT-PCR, cloning, sequencing, and genetic analyses were performed on eight plasma follow-up samples. Extensive increasing intra- and intersample variation was observed. This is the first long-term (>10 years) follow-up of the genetic variability of an HIV-1 group O-infected individual. As the course of the disease in the HIV-1 ANT70-infected woman was similar in many aspects to that of group M-infected individuals, it remains to be elucidated whether the changes observed in the V3 loop are critical for disease progression.

Adult↗
PubMed1999

Interpatient genetic variability of HIV-1 group O.

OBJECTIVE: To analyse the genetic and phylogenetic characteristics of HIV-1 group O viruses. MATERIALS AND METHODS: The env gene, encoding the gp160 glycoprotein, and a partial p24-encoding gag gene fragment of a Cameroonian (CA9) and a Gabonese (VI686) HIV-1 group O virus, isolated from cultured peripheral blood mononuclear cells of symptomatic patients, were sequenced, aligned with other representatives of group O for which the same region has been documented, and genetically and phylogenetically analysed. RESULTS: Phylogenetic analysis of the env gene (gp160) revealed that CA9, VI686, ANT70, and four Ha strains formed a separate cluster, which was supported by 100% of all bootstrap trees. In addition, these seven isolates were part of the same clade in the p24 phylogeny. VAU and MVP5180 may represent two other subtypes. CONCLUSION: We have characterized two group O viruses, originating from Cameroon and Gabon, which show a close evolutionary relationship to ANT70 and four Ha strains based on the entire env gene, suggestive of a first group O subgroup, tentatively named the HIV-1 group O env ANT70 clade or subtype.

Amino Acid Sequence↗