42 results on '"van der Ryst, E."'
Search Results
2. Highly prevalent Russian HIV-1 V3-loop sequence variants are susceptible to maraviroc
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Lewis, ME, primary, Jubb, B, additional, Simpson, P, additional, Lopatukhin, A, additional, Kireev, D, additional, Bobkova, M, additional, Craig, C, additional, van der Ryst, E, additional, Westby, M, additional, and Butler, SL, additional more...
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- 2021
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3. V3-Loop genotypes do not predict maraviroc susceptibility of CCR5-tropic virus or clinical response through week 48 in HIV-1–infected, treatment-experienced persons receiving optimized background regimens
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Lewis, ME, primary, Simpson, P, additional, Mori, J, additional, Jubb, B, additional, Sullivan, J, additional, McFadyen, L, additional, van der Ryst, E, additional, Craig, C, additional, Robertson, DL, additional, and Westby, M, additional more...
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- 2021
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4. Nutritional status of HIV-1 seropositive patients in the Free State Province of South Africa: Anthropometric and dietary profile
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Dannhauser, A, van Staden, AM, van der Ryst, E, Nel, M, Marais, N, Erasmus, E, Attwood, EM, Barnard, HC, and le Roux, GD
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- 1999
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5. Correlation Among Total Lymphocyte Count, Absolute CD4+ Count, and CD4+ Percentage in a Group of HIV-1-Infected South African Patients
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van der Ryst E, Steyn M, van der Westhuizen M, Gina Joubert, Kotze M, Christine S Venter, van Staden M, and Pieters H
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Adult ,Male ,Cellular immunity ,medicine.medical_specialty ,Adolescent ,Lymphocyte ,Immunology ,Population ,Human immunodeficiency virus (HIV) ,HIV Infections ,Biology ,medicine.disease_cause ,Sensitivity and Specificity ,Spearman's rank correlation coefficient ,Gastroenterology ,Correlation ,South Africa ,Virology ,Internal medicine ,medicine ,Humans ,Immunology and Allergy ,Lymphocyte Count ,education ,Aged ,Likelihood Functions ,education.field_of_study ,Middle Aged ,Confidence interval ,CD4 Lymphocyte Count ,medicine.anatomical_structure ,HIV-1 ,Female ,CD8 - Abstract
Depletion of CD4+ T cells is one of the hallmarks of progression of HIV-1 infection. However, measurement of the CD4+ T-cell count is expensive and often unavailable in less developed areas. Previous studies have suggested that the total lymphocyte count (TLC) can be used to predict a low absolute CD4+ T-cell count. To determine the relationship between TLC and CD4+ T-cell count in HIV-1-infected South African patients, 2777 HIV-1-seropositive patients visiting the Immunology clinic at the Pelonomi Hospital in Bloemfontein, South Africa from April 1991 to April 1997 were included in the study. In total, 3237 observations were used to determine sensitivity, specificity, and likelihood ratios, with 95% confidence intervals, of various cutpoints of the TLC to predict an absolute CD4+ T-cell count of200 cells/mm3, CD4+ percentage20%, and CD4+ percentage15%. Spearman rank correlations were calculated between TLC and CD4+ T cells, CD4+ percentage and CD8+ T cells, as well as between CD4+ and CD8+ T cells. Results demonstrated that a TLC of 2 x 10(9)/L or less had a sensitivity of 90.3% to detect patients with a CD4+ T-cell count of200 cells/mm3, but a specificity of only 53.7%. When the TLC cutoff value was lowered, specificity increased but sensitivity decreased. For the observations as a group, a correlation (r = 0.704) between CD4+ T-cell count and TLC was demonstrated, but if the patients were divided into three groups according to their CD4+ T-cell count, this correlation weakened considerably. Therefore, although TLC shows a correlation with CD4+ T-cell count, it is not a good predictor of the CD4+ T-cell count in this population and should preferably not be used in the clinical care of HIV/AIDS patients.Measurement of CD4 T-cell counts to monitor progression of HIV-1 infection is expensive and often unavailable in developing countries. Previous studies have suggested that the total lymphocyte count (TLC) can be used to predict a low absolute CD4 T-cell count. This possibility was explored in a study of 2777 HIV-1-positive patients attending the immunology clinic at the Pelonomi Hospital in Bloemfontein, South Africa, in 1991-97. A total of 3237 paired observations were used to determine the sensitivity, specificity, and likelihood ratios of various TLC cutoff points to predict absolute CD4 T-cell counts. A TLC of 2x109/l or less had a sensitivity of 90.3% to detect patients with a CD4 T-cell count of less than 200 cells/cu. mm, but a specificity of only 53.7%. When the TLC cutoff value was lowered, specificity increased but sensitivity decreased. Overall, there was a correlation between CD4 T-cell count and TLC (r = 0.704); however, this correlation was weakened considerably when patients were stratified into three groups according to their CD4 T-cell count. These findings suggest that use of TLC to predict the CD4 T-cell count should not be used in the clinical care of HIV/AIDS patients. Rather, informed decision making based on the clinical condition and risk factors for developing opportunistic infections is recommended. more...
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- 1998
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6. Efficacy and safety of Maraviroc vs. Efavirenz in treatment-naive patients with HIV-1: 5-year findings
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Cooper, DA, Heera, J, Ive, P, Botes, M, Dejesus, E, Burnside, R, Clumeck, N, Walmsley, S, Lazzarin, A, Mukwaya, G, Saag, M, Van Der Ryst, E, Cooper, DA, Heera, J, Ive, P, Botes, M, Dejesus, E, Burnside, R, Clumeck, N, Walmsley, S, Lazzarin, A, Mukwaya, G, Saag, M, and Van Der Ryst, E more...
- Abstract
Objective: Maraviroc, a chemokine co-receptor type 5 (CCR5) antagonist, has demonstrated comparable efficacy and safety to efavirenz, each in combination with zidovudine/lamivudine, over 96 weeks in the Maraviroc vs. Efavirenz Regimens as Initial Therapy (MERIT) study. Here we report 5-year findings. Design: A randomized, double-blind, multicenter phase IIb/III study with an open-label extension phase. Methods: Treatment-naive patients with CCR5-tropic HIV-1 infection (Trofile) received maraviroc 300mg twice daily or efavirenz 600mg once daily, and zidovudine/lamivudine 300 mg/150mg twice daily. After the last patient's week 96 visit, the study was unblinded and patients could enter a nominal 3-year open-label phase. Endpoints at the 5-year nominal visit (week 240) included proportion of patients (CCR5 tropism reconfirmed by enhanced sensitivity Trofile) with viral load (plasma HIV-1 RNA) below 50 and 400 copies/ml, and change from baseline in CD4+ cell count, as well as safety. Results: The proportion of patients maintaining viral load below 50 copies/ml was similar between treatment arms throughout the study and at week 240 (maraviroc 50.8% vs. efavirenz 45.9%). Maraviroc-treated patients had a greater increase from baseline in mean CD4+ cell count than efavirenz-treated patients at week 240 (293 vs. 271 cells/μl, respectively). Fewer patients on maraviroc vs. efavirenz experienced treatment-related adverse events (68.9 vs. 81.7%) and discontinued as a result of any adverse event (10.6 vs. 21.3%). Conclusion: Maraviroc maintained similar long-term antiviral efficacy to efavirenz over 5 years in treatment-naive patients with CCR5-tropic HIV-1. Maraviroc was generally well tolerated with no unexpected safety findings or evidence of long-term safety concerns. © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins. more...
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- 2014
7. Molecular epidemiology of 58 new African T-Cell leukemia virus type 1 (HTLV-1) strains : identification of a new and distinct HTLV-1 molecular subtype in Central Africa and in Pygmies
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Mahieux, R., Ibrahim, F., Mauclere, P., Hervé, V., Michel, P., Tekaia, F., Chappey, C., Garin, B., Van Der Ryst, E., Guillemain, B., Ledru, E., Delaporte, Eric, The, G. de, and Gessain, A.
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GENOME ,EPIDEMIOLOGIE ,HTLV-1 ,TECHNIQUE PCR ,VIRUS ,PHYLOGENIE ,SOUCHE ,VARIABILITE GENETIQUE - Abstract
To gain new insights on the origin, evolution, and modes of dissemination of human T-cell leukemia virus type 1 (HTLV-1), we performed a molecular analysis of 58 new African HTLV-1 strains (18 from West Africa, 36 from Central Africa, and 4 from South Africa) originating from 13 countries. Of particular interest were eight strains from Pygmies of remote areas of Cameroon and the Central African Republic (CAR), considered to be the oldest inhabitants of these regions. Eight long-term activated T-cell lines producing HTLV-1 gag and env antigens were established from peripheral blood mononuclear cell cultures of HTLV-1 seropositive individuals, including three from Pygmies. A fragment of the env gene encompassing most of the gp21 transmembrane region was sequenced for the 58 new strains, while the complete long terminal repeat (LTR) region was sequenced for 9 strains, including 4 from Pygmies. Comparative sequence analyses and phylogenetic studies performed on both the env and LTR regions by the neighbor-joining and DNA parsimony methods demonstrated that all 22 strains from West and South Africa belong to the widespread cosmopolitan subtype (also called HTLV-1 subtype A). Within or alongside the previously described Zairian cluster (HTLV-1 subtype B), we discovered a number of new HTLV-1 variants forming different subgroups corresponding mainly to the geographical origins of the infected persons, Cameroon, Gabon, and Zaire. Six of the eight Pygmy strains clustered together within this Central African subtype, suggesting a common origin. Furthermore, three new strains (two originating from Pygmies from Cameroon and the CAR, respectively, and one from a Gabonese individual) were particularly divergent and formed a distinct new phylogenetic cluster, characterized by specific mutations and occupying in most analyses a unique phylogenetic position between the large Central African genotype and the Melanesian subtype... (D'après résumé d'auteur) more...
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- 1997
8. Lersivirine: a new NNRTI active across HIV-1 subtypes with a unique resistance profile
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Mori, J, primary, Westby, M, additional, Tawadrous, M, additional, van der Ryst, E, additional, and Charles, C, additional
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- 2010
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9. Randomised placebo-controlled trial to evaluate the effect of vitamin A on mother-to-child transmission of HIV-1 in Bloemfontein
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Chikobvu, Perpetual, Joubert, G., Schall, R., Van der Ryst, E., Chikobvu, Perpetual, Joubert, G., Schall, R., and Van der Ryst, E.
- Abstract
English: Mother-to-child (vertical) transmission is the primary means by which young children acquire human immunodeficiency virus type 1 (HIV -1) infection. Anti-retrovirals such as Zidovudine and nevirapine can reduce vertical transmission of HIV significantly, but this treatment is still largely unaffordable in Africa. Maternal vitamin A deficiency is suspected to enhance vertical transmission of HIV. Furthermore, vitamin A is known to act as a coenzyme to the immune process. Therefore, a double-blind randomized placebo controlled trial to assess the effect of vitamin A supplementation on vertical transmission of HIV was launched in Bloemfontein in 1997. A total of 2949 pregnant women attending the antenatal clinics at Pelonomi and Universitas hospitals and the Mangaung University Community Partnership clinic were counselled for HIV testing, and 2543 were willing to be screened by HIV testing for possible inclusion in the trial. Of the women screened 595 (23.4%) were HIV positive, and 303 of these were willing to participate in the trial. 152 women were randomized to vitamin A treatment and 151 to placebo treatment. Patients were seen at 2 monthly intervals in the antenatal phase. Post-natally mother-infants pairs were seen when the infant was 1 month old, 3 months old, and thereafter, 3 monthly till 18 months old. A total of 191 patients (63% of all the study participants) missed one or more visits and had to be traced. Of the 303 patients included in the study 158 had a conclusive infant HIV test result (patients in the Intention To Treat (!TT) analysis population) and 104 patients had a conclusive infant mv test result when the baby was 3 months old (patients in the Per Protocol (PP) analysis population). Of 158 patients, in the ITT population 73 were in the vitamin A group and 85 in the placebo group. Per treatment group the baseline characteristics of those in the IIT population and those who are not, did not differ significanti y. The mv transmission rates, Afrikaans: Moeder-na-kind (vertikale) oordrag is die algemeenste mamer waarop Jong kinders menslike immuniteitsgebrek virus tipe 1 (MIV -1) opdoen. Antiretrovirale middels soos Zidovudine en nevirapine kan die vertikale oordrag van MIV betekenisvol verlaag, maar hierdie behandeling is steeds meestal nie bekostigbaar in Afrika nie. Daar word vermoed dat moederlike vitamine A gebrek die vertikale oordrag van MIV bevorder. Verder is dit bekend dat vitamine A 'n ko-ensiem is tot die immuunproses. Daarom is 'n gerandomiseerde dubbelblinde plasebo gekontrolleerde proef om die effek van vitamine A supplementasie op die vertikale oordrag van HIV te bepaal in 1997 in Bloemfontein van stapel gestuur. 'n Totaal van 2949 swanger vroue wat die voorgeboorteklinieke by die Universitas en Pelonomi Hospitale en die Mangaung University Community Partnership Project kliniek bygewoon het, het berading vir MIV-toetsing ontvang, en 2543 was bereid om deur MIVtoetsing gesif te word vir moontlike insluiting in die proef. Van die vroue wat gesif is, was 595 (23.4%) MIV-positief, en 303 van hulle het ingewillig om aan die studie deel te neem. 152 MIV positiewe vroue is gerandomiseer om vitamine A behandeling te ontvang en 151 plasebo behandeling. Pasiënte is tydens die voorgeboorte fase 2 maandeliks gesien. In die nageboorte fase is moeder-baba pare gesien toe die baba 1 maand oud was, 3 maande oud en daarna 3 maandeliks tot 18 maande oud. 'n Totaal van 191 pasiënte (63% van al die studiedeelnemers) het een of meer besoek gemis en moes opgespoor word. Van die 303 vroue wat ingesluit is in die studie, het 158 'n afdoende baba-MIV toetsuitslag gehad (pasiënte in die Beplan om te Behandel (BB) ontledingspopulasie) en 104 pasiënte het 'n afdoende baba MIV toetsuitslag gehad toe die baba 3 maade oud was (pasiënte in die Per Protokol (PP) ontledingspopulasie). Van die 158 pasiënte in die BB populasie was 73 in die vitamine A groep en 85 in die plasebo groep. Per behandelingsgroep was daar geen bet, South African Medical Research Council (MRC), University of the Free State Central Research Fund, Foundation for Research Development (FRD) more...
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- 2002
10. Rift Valley Fever Virus: a Seroepidemiologic Study of Small Terrestrial Vertebrates in South Africa
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Pretorius, A., primary, van der Ryst, E., additional, Oelofsen, M. J., additional, and Smith, M. S., additional
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- 1997
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11. Molecular epidemiology of 58 new African human T-cell leukemia virus type 1 (HTLV-1) strains: identification of a new and distinct HTLV-1 molecular subtype in Central Africa and in Pygmies
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Mahieux, R, primary, Ibrahim, F, additional, Mauclere, P, additional, Herve, V, additional, Michel, P, additional, Tekaia, F, additional, Chappey, C, additional, Garin, B, additional, Van Der Ryst, E, additional, Guillemain, B, additional, Ledru, E, additional, Delaporte, E, additional, de The, G, additional, and Gessain, A, additional more...
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- 1997
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12. Failure of a human immunodeficiency virus type 1 (HIV-1) subtype B-derived vaccine to prevent infection of chimpanzees by an HIV-1 subtype E strain
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Girard, M, primary, Yue, L, additional, Barré-Sinoussi, F, additional, van der Ryst, E, additional, Meignier, B, additional, Muchmore, E, additional, and Fultz, P N, additional
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- 1996
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13. Allelic frequencies of host genetic variants influencing susceptibility to HIV-1 infection and disease in South African populations.
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Williamson, Carolyn, Loubser, Shayne A., Brice, Belinda, Joubert, Gina, Smit, Teresa, Thomas, Robin, Visagie, Melanie, Cooper, Mark, van der Ryst, Elna, Williamson, C, Loubser, S A, Brice, B, Joubert, G, Smit, T, Thomas, R, Visagie, M, Cooper, M, and van der Ryst, E more...
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- 2000
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14. First prospective comparison of genotypic versus phenotypic tropism assays in predicting virologic responses to maraviroc in a phase 3 study.
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Heera J, Valluri SR, Craig C, Fang A, Thomas N, Meyer RD, Lewis ME, van der Ryst E, and Demarest J
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- Adult, Anti-HIV Agents therapeutic use, Female, HIV-1 genetics, Humans, Male, Maraviroc immunology, Middle Aged, Prospective Studies, Treatment Outcome, HIV Infections drug therapy, HIV Infections immunology, HIV Infections virology, Maraviroc therapeutic use, Tropism
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Maraviroc (MVC, a CCR5 antagonist) is only fully active against CCR5 tropic [R5] HIV-1, and tropism testing is required prior to initiating treatment. The MODERN study prospectively compared genotypic (GTT) and phenotypic (Trofile®) tropism testing with treatment-naive HIV-1-infected participants randomized 1:1 to either GTT or Trofile tropism assessments. Participants with R5 virus were randomized 1:1 to receive darunavir/ritonavir (DRV/r) with either MVC or tenofovir/emtricitabine. Screening samples were also retrospectively tested using the alternative assay. Positive predictive values (PPVs) for each assay were estimated using both the observed MVC+DRV/r response rate (HIV-1 RNA <50 copies/mL at Week 48) and model-based response estimates. The observed MVC+DRV/r response rate was 146/181 (80.7%) for GTT versus 160/215 (74.4%) for Trofile, with a stratification adjusted difference of 6.6% (95% CI, -1.5% to 14.7%) in favor of GTT. The model-based PPV estimates (±standard error) were 80.5% (±2.38) and 78.0% (±2.35) for GTT and Trofile, respectively (difference, 2.5%; 95% CI, -2.0% to 7.0%). Most participants had R5 results using both assays (285/396; 72%) and, of those, 79.3% (226/285) had HIV-1 RNA <50 copies/mL at Week 48. Both the genotypic and phenotypic tropism assays evaluated can effectively predict treatment response to MVC. more...
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- 2019
15. Incidence of CXCR4 tropism and CCR5-tropic resistance in treatment-experienced participants receiving maraviroc in the 48-week MOTIVATE 1 and 2 trials.
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Jubb B, Lewis M, McFadyen L, Simpson P, Mori J, Chan P, Weatherley B, van der Ryst E, Westby M, and Craig C
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- CD4 Lymphocyte Count, Double-Blind Method, Drug Resistance, Viral, HIV-1 genetics, HIV-1 immunology, Humans, Placebos, RNA, Viral analysis, CCR5 Receptor Antagonists therapeutic use, HIV Infections drug therapy, Maraviroc therapeutic use, Receptors, CCR5 physiology, Receptors, CXCR4 physiology
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- 2019
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16. Clonal analysis of HIV-1 genotype and function associated with virologic failure in treatment-experienced persons receiving maraviroc: Results from the MOTIVATE phase 3 randomized, placebo-controlled trials.
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Lewis M, Mori J, Toma J, Mosley M, Huang W, Simpson P, Mansfield R, Craig C, van der Ryst E, Robertson DL, Whitcomb JM, and Westby M
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- Adult, Female, HIV Infections pathology, Humans, Male, Maraviroc adverse effects, Middle Aged, Treatment Failure, Viral Tropism drug effects, Genotype, HIV Infections drug therapy, HIV Infections genetics, HIV-1 genetics, Maraviroc administration & dosage, Phylogeny, Viral Tropism genetics
- Abstract
Detailed clonal phenotypic/genotypic analyses explored viral-escape mechanisms during maraviroc-based therapy in highly treatment-experienced participants from the MOTIVATE trials. To allow real-time assessment of samples while maintaining a blind trial, the first 267 enrolled participants were selected for evaluation. At failure, plasma samples from 20/50 participants (16/20 maraviroc-treated) with CXCR4-using virus and all 38 (13 maraviroc-treated) with CCR5-tropic virus were evaluated. Of those maraviroc-treated participants with CXCR4-using virus at failure, genotypic and phenotypic clonal tropism determinations showed >90% correspondence in 14/16 at Day 1 and 14/16 at failure. Phylogenetic analysis of clonal sequences detected pre-treatment progenitor CXCR4-using virus, or on-treatment virus highly divergent from the Day 1 R5 virus, excluding possible co-receptor switch through maraviroc-mediated evolution. Re-analysis of pre-treatment samples using the enhanced-sensitivity Trofile® assay detected CXCR4-using virus pre-treatment in 16/20 participants failing with CXCR4-using virus. Post-maraviroc reversion of CXCR4-use to CCR5-tropic occurred in 7/8 participants with follow-up, suggesting selective maraviroc inhibition of CCR5-tropic variants in a mixed-tropic viral population, not emergence of de novo mutations in CCR5-tropic virus, as the main virologic escape mechanism. Maraviroc-resistant CCR5-tropic virus was observed in plasma from 5 treated participants with virus displaying reduced maximal percent inhibition (MPI) but no evidence of IC50 change. Env clones with reduced MPI showed 1-5 amino acid changes specific to each V3-loop region of env relative to Day 1. However, transferring on-treatment resistance-associated changes using site-directed mutagenesis did not always establish resistance in Day 1 virus, and key 'signature' mutation patterns associated with reduced susceptibility to maraviroc were not identified. Evolutionary divergence of the CXCR4-using viruses is confirmed, emphasizing natural selection not influenced directly by maraviroc; maraviroc simply unmasks pre-existing lineages by inhibiting the R5 virus. For R5-viral failure, resistance development through drug selection pressure was uncommon and manifested through reduced MPI and with virus strain-specific mutational patterns., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: RM is an employee of Pfizer and owns stock in the company. CC, ML, and EV are not employed but are affiliated to The Research Network, Ltd, which administers the contract with Pfizer for work on the maraviroc program, including the finalization of the analysis and preparation of the submitted work. CC, ML, and EV were previously employed by Pfizer; EV, JM, ML, MM, and MW were employed during the conduct of the trial. CC owns stock in GlaxoSmithKline. JT, WH, and JMW are employees of Monogram Biosciences. DLR reports a grant from the Medical Research Council (MRC; G1001806/1) and consultancy fees from Pfizer during the conduct of the study. JT reports a grant from Small Business Innovation Research (Grant number: 1 R21 AI114399) outside the scope of the submitted work, and a fee for service from Pfizer during the conduct of the study; in addition, JT has a patent US 9,581,595 B2 issued. Pfizer is one of the beneficiaries of the ViiV Healthcare Joint Venture along with GlaxoSmithKline and Shinogi. This does not alter our adherence to PLOS ONE policies on sharing data and materials. more...
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- 2018
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17. Maraviroc - A CCR5 Antagonist for the Treatment of HIV-1 Infection.
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Van Der Ryst E
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- 2015
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18. Efficacy and safety of maraviroc vs. efavirenz in treatment-naive patients with HIV-1: 5-year findings.
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Cooper DA, Heera J, Ive P, Botes M, Dejesus E, Burnside R, Clumeck N, Walmsley S, Lazzarin A, Mukwaya G, Saag M, and van Der Ryst E
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- Adolescent, Adult, Aged, Alkynes, Benzoxazines adverse effects, Benzoxazines therapeutic use, CD4 Lymphocyte Count, Cyclohexanes adverse effects, Cyclohexanes therapeutic use, Cyclopropanes, Double-Blind Method, Drug-Related Side Effects and Adverse Reactions epidemiology, Female, Humans, Male, Maraviroc, Middle Aged, Treatment Outcome, Triazoles adverse effects, Triazoles therapeutic use, Viral Load, Young Adult, Anti-HIV Agents adverse effects, Anti-HIV Agents therapeutic use, Antiretroviral Therapy, Highly Active adverse effects, Antiretroviral Therapy, Highly Active methods, HIV Infections drug therapy, HIV Infections virology, HIV-1 isolation & purification
- Abstract
Objective: Maraviroc, a chemokine co-receptor type 5 (CCR5) antagonist, has demonstrated comparable efficacy and safety to efavirenz, each in combination with zidovudine/lamivudine, over 96 weeks in the Maraviroc vs. Efavirenz Regimens as Initial Therapy (MERIT) study. Here we report 5-year findings., Design: A randomized, double-blind, multicenter phase IIb/III study with an open-label extension phase., Methods: Treatment-naive patients with CCR5-tropic HIV-1 infection (Trofile) received maraviroc 300 mg twice daily or efavirenz 600 mg once daily, and zidovudine/lamivudine 300 mg/150 mg twice daily. After the last patient's week 96 visit, the study was unblinded and patients could enter a nominal 3-year open-label phase. Endpoints at the 5-year nominal visit (week 240) included proportion of patients (CCR5 tropism re-confirmed by enhanced sensitivity Trofile) with viral load (plasma HIV-1 RNA) below 50 and 400 copies/ml, and change from baseline in CD4(+) cell count, as well as safety., Results: The proportion of patients maintaining viral load below 50 copies/ml was similar between treatment arms throughout the study and at week 240 (maraviroc 50.8% vs. efavirenz 45.9%). Maraviroc-treated patients had a greater increase from baseline in mean CD4(+) cell count than efavirenz-treated patients at week 240 (293 vs. 271 cells/μl, respectively). Fewer patients on maraviroc vs. efavirenz experienced treatment-related adverse events (68.9 vs. 81.7%) and discontinued as a result of any adverse event (10.6 vs. 21.3%)., Conclusion: Maraviroc maintained similar long-term antiviral efficacy to efavirenz over 5 years in treatment-naive patients with CCR5-tropic HIV-1. Maraviroc was generally well tolerated with no unexpected safety findings or evidence of long-term safety concerns. more...
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- 2014
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19. An exploratory survey measuring stigma and discrimination experienced by people living with HIV/AIDS in South Africa: the People Living with HIV Stigma Index.
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Dos Santos MM, Kruger P, Mellors SE, Wolvaardt G, and van der Ryst E
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- Adolescent, Adult, Cross-Sectional Studies, Employment statistics & numerical data, Female, Health Services Accessibility statistics & numerical data, Humans, Interviews as Topic, Male, Middle Aged, Self Disclosure, South Africa epidemiology, Surveys and Questionnaires, Young Adult, HIV Infections psychology, Prejudice statistics & numerical data, Stereotyping
- Abstract
Background: The continued presence of stigma and its persistence even in areas where HIV prevalence is high makes it an extraordinarily important, yet difficult, issue to eradicate. The study aimed to assess current and emerging HIV/AIDS stigma and discrimination trends in South Africa as experienced by people living with HIV/AIDS (PLHIV)., Methods: The PLHIV Stigma Index, a questionnaire that measures and detects changing trends in relation to stigma and discrimination experienced by PLHIV, was used as the survey tool. The study was conducted in 10 clinics in four provinces supported by the Foundation for Professional Development (FPD), with an interview total of 486 PLHIV. A cross-sectional design was implemented in the study, and both descriptive and inferential analysis was conducted on the data., Results: Findings suggest that PLHIV in this population experience significant levels of stigma and discrimination that negatively impact on their health, working and family life, as well as their access to health services. Internalised stigma was prominent, with many participants blaming themselves for their status., Conclusion: The findings can be used to develop and inform programmes and interventions to reduce stigma experienced by PLHIV. The current measures for dealing with stigma should be expanded to incorporate the issues related to health, education and discrimination experienced in the workplace, that were highlighted by the study. more...
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- 2014
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20. Hepatic safety and tolerability in the maraviroc clinical development program.
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Ayoub A, Alston S, Goodrich J, Heera J, Hoepelman AI, Lalezari J, Mchale M, Nelson M, van der Ryst E, and Mayer H
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- Anti-HIV Agents pharmacology, Cyclohexanes pharmacology, Humans, Maraviroc, Triazoles pharmacology, CCR5 Receptor Antagonists, Cyclohexanes antagonists & inhibitors, HIV Infections drug therapy, HIV-1 drug effects, Triazoles antagonists & inhibitors
- Abstract
Maraviroc is the first CCR5 antagonist to be approved for the treatment of HIV-1 infection. It is generally well tolerated, with a similar side-effect profile to placebo in controlled studies. Many agents used to treat HIV disease are associated with the potential for hepatotoxicity. The hepatic effects of maraviroc were analyzed across all Pfizer-sponsored maraviroc clinical trials, in which 2350 volunteers received maraviroc. Although sporadic hepatic enzyme abnormalities were reported in 34 phase 1/2a studies of up to 28-day duration, they demonstrated no dose relationship or association with hyperbilirubinemia. In the four phase 2b/3 studies in antiretroviral -naive and antiretroviral-experienced patients, there was no significant imbalance in hepatic enzyme abnormalities or hepatobiliary adverse events in maraviroc versus comparator arms up to week 96. The findings were similar in patients coinfected with hepatitis B and/or C virus, although the number of coinfected patients was small. No patient met the strict definition for Hy's Law. Two participants reported severe hepatotoxicity and although other potential causes were present, the contribution of maraviroc to these events could not be excluded. This analysis suggests that maraviroc does not present significant risks to hepatic safety when taken at the recommended doses in the populations studied. more...
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- 2010
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21. Maraviroc versus efavirenz, both in combination with zidovudine-lamivudine, for the treatment of antiretroviral-naive subjects with CCR5-tropic HIV-1 infection.
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Cooper DA, Heera J, Goodrich J, Tawadrous M, Saag M, Dejesus E, Clumeck N, Walmsley S, Ting N, Coakley E, Reeves JD, Reyes-Teran G, Westby M, Van Der Ryst E, Ive P, Mohapi L, Mingrone H, Horban A, Hackman F, Sullivan J, and Mayer H more...
- Subjects
- Adolescent, Adult, Aged, Alkynes, Anti-HIV Agents standards, Anti-Retroviral Agents, Antiviral Agents pharmacology, Benzoxazines pharmacology, Benzoxazines standards, Cyclohexanes pharmacology, Cyclohexanes standards, Cyclopropanes, Double-Blind Method, Drug Combinations, Drug Resistance, Viral, Drug Therapy, Combination, Female, HIV-1 physiology, Humans, Lamivudine administration & dosage, Male, Maraviroc, Middle Aged, Receptors, CCR5 metabolism, Treatment Outcome, Triazoles pharmacology, Triazoles standards, Viral Load, Viral Tropism, Young Adult, Zidovudine administration & dosage, Anti-HIV Agents pharmacology, Benzoxazines therapeutic use, CCR5 Receptor Antagonists, Cyclohexanes therapeutic use, HIV Infections drug therapy, HIV-1 drug effects, Triazoles therapeutic use
- Abstract
Background: The MERIT (Maraviroc versus Efavirenz in Treatment-Naive Patients) study compared maraviroc and efavirenz, both with zidovudine-lamivudine, in antiretroviral-naive patients with R5 human immunodeficiency virus type 1 (HIV-1) infection., Methods: Patients screened for R5 HIV-1 were randomized to receive efavirenz (600 mg once daily) or maraviroc (300 mg once or twice daily) with zidovudine-lamivudine. Coprimary end points were proportions of patients with a viral load <400 and <50 copies/mL at week 48; the noninferiority of maraviroc was assessed., Results: The once-daily maraviroc arm was discontinued for not meeting prespecified noninferiority criteria. In the primary 48-week analysis (n = 721), maraviroc was noninferior for <400 copies/mL (70.6% for maraviroc vs 73.1% for efavirenz) but not for <50 copies/mL (65.3% vs 69.3%) at a threshold of -10%. More maraviroc patients discontinued for lack of efficacy (11.9% vs 4.2%), but fewer discontinued for adverse events (4.2% vs 13.6%). In a post hoc reanalysis excluding 107 patients (15%) with non-R5 screening virus by the current, more sensitive tropism assay, the lower bound of the 1-sided 97.5% confidence interval for the difference between treatment groups was above -10% for each end point., Conclusions: Twice-daily maraviroc was not noninferior to efavirenz at <50 copies/mL in the primary analysis. However, 15% of patients would have been ineligible for inclusion by a more sensitive screening assay. Their retrospective exclusion resulted in similar response rates in both arms Trial registration. ClinicalTrials.gov identifier: (NCT00098293) . more...
- Published
- 2010
- Full Text
- View/download PDF
22. A double-blind, placebo-controlled trial of maraviroc in treatment-experienced patients infected with non-R5 HIV-1.
- Author
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Saag M, Goodrich J, Fätkenheuer G, Clotet B, Clumeck N, Sullivan J, Westby M, van der Ryst E, and Mayer H
- Subjects
- Adult, Aged, Cyclohexanes adverse effects, Double-Blind Method, Female, Genotype, HIV genetics, HIV Fusion Inhibitors adverse effects, Humans, Least-Squares Analysis, Male, Maraviroc, Middle Aged, Patient Selection, Phenotype, Placebos, Triazoles adverse effects, Viral Load, Young Adult, Cyclohexanes therapeutic use, HIV Fusion Inhibitors therapeutic use, HIV Infections drug therapy, Triazoles therapeutic use
- Abstract
Background: Maraviroc, a CCR5 antagonist, is active against R5 but not X4 or dual- or mixed-tropic strains of human immunodeficiency virus type 1 (HIV-1). A phase 2b study was conducted to determine the safety and efficacy of maraviroc in combination with optimized background therapy in treatment-experienced patients infected with dual- or mixed-tropic HIV-1., Methods: Treatment-experienced patients with an HIV-1 RNA level 5000 copies/mL who had received 3 classes of drugs and/or were infected with virus resistant to 2 drug classes and were infected with non-R5 HIV-1 were randomized to receive optimized background therapy plus maraviroc (once or twice daily) or placebo. The primary end point was change in HIV-1 RNA level from baseline to 24 weeks., Results: Among 167 patients infected with dual- or mixed-tropic HIV-1, baseline mean HIV-1 RNA levels were >5 log(10) copies/mL and median CD4(+) cell counts were <50 cells/microL. From baseline to 24 weeks, patients who received placebo demonstrated a mean decrease in HIV-1 RNA levels of 0.97 log(10) copies/mL, compared with mean decreases of 0.91 and 1.20 log(10) copies/mL for those who received maraviroc once (P =.83) or twice (P +.38) daily, respectively. Mean increases in CD4(+) cell counts from baseline were 36 cells/microL for patients who received placebo, 60 cells/microL among patients who received maraviroc once daily, and 62 cells/microL among patients who received maraviroc twice daily. The incidences of serious adverse events were similar among groups., Conclusions: In this exploratory study involving extensively treatment-experienced patients with advanced, non-R5 HIV-1 infection, neither superiority nor noninferiority was statistically demonstrated for either maraviroc dosage compared with placebo at 24 weeks of treatment., Trial Registration: Clinicaltrials.gov identifier NCT00098748 . more...
- Published
- 2009
- Full Text
- View/download PDF
23. Assessment of the pharmacokinetics, safety and tolerability of maraviroc, a novel CCR5 antagonist, in healthy volunteers.
- Author
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Abel S, van der Ryst E, Rosario MC, Ridgway CE, Medhurst CG, Taylor-Worth RJ, and Muirhead GJ
- Subjects
- Administration, Oral, Adolescent, Adult, Anti-HIV Agents pharmacokinetics, Cyclohexanes adverse effects, Female, Humans, Male, Maraviroc, Middle Aged, Statistics as Topic, Triazoles adverse effects, Anti-HIV Agents adverse effects, CCR5 Receptor Antagonists, Cyclohexanes pharmacokinetics, HIV Infections drug therapy, Triazoles pharmacokinetics
- Abstract
Aims: To evaluate the pharmacokinetics, safety and tolerability of single and multiple oral doses of maraviroc in healthy volunteers., Methods: Three double-blind, placebo-controlled, dose-escalation studies with either single or multiple doses of maraviroc were conducted in healthy volunteers. Plasma and urine samples were collected to investigate the pharmacokinetics of maraviroc and evaluate any changes with respect to dose and duration/frequency of dosing. Safety and toleration of maraviroc were also assessed., Results: Maraviroc is rapidly absorbed following oral administration, and plasma T(max) is achieved within 0.5-4.0 h postdose. Steady-state plasma concentrations are achieved after 7 consecutive days of dosing. Although the pharmacokinetics of maraviroc is nonproportional over the dose range studied (3-1200 mg), the degree of nonproportionality is small at clinically relevant doses. Renal clearance is approximately 10-12 l h(-1) and appears unaffected by increasing maraviroc doses. Maraviroc does not significantly modulate the activity of CYP2D6 or CYP3A4 at clinically relevant doses. There were no serious adverse events in any of these studies, and doses up to 900 mg were generally well tolerated, with postural hypotension being the dose-limiting event. There was no pattern or dose relationship observed with maraviroc with regard to laboratory abnormalities, including hepatic transaminases. No clinically significant increases in QTc were noted at clinically relevant doses., Conclusions: Maraviroc is absorbed into the systemic circulation and reaches steady state by day 7 of multiple dosing. It does not significantly influence the activity of major drug-metabolizing enzymes and is well tolerated at clinically relevant doses, with most adverse events being mild or moderate. more...
- Published
- 2008
- Full Text
- View/download PDF
24. Population pharmacokinetic/pharmacodynamic analysis of CCR5 receptor occupancy by maraviroc in healthy subjects and HIV-positive patients.
- Author
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Rosario MC, Jacqmin P, Dorr P, James I, Jenkins TM, Abel S, and van der Ryst E
- Subjects
- Computer Simulation, Humans, Maraviroc, Models, Biological, Models, Statistical, Randomized Controlled Trials as Topic, Viral Load, Anti-HIV Agents pharmacokinetics, CCR5 Receptor Antagonists, Cyclohexanes pharmacokinetics, HIV Infections drug therapy, Triazoles pharmacokinetics
- Abstract
Background: Maraviroc, a noncompetitive antagonist of the CCR5 coreceptor, was recently approved in the USA as a treatment of HIV infection. For antiretroviral agents that target the virus, antiviral effect can be related to some extent to plasma drug concentrations. For CCR5 antagonists that target the host cells, receptor occupancy in vivo might be a better predictor of efficacy. AIMS To develop a population pharmacokinetic (PK)-pharmacodynamic (PD) model that describes CCR5 receptor occupancy by maraviroc after oral administration at different doses in healthy volunteers and HIV-positive patients and to assess the relevance of receptor occupancy in predicting the decrease in viral load (HIV-1 RNA copies ml(-1)) in HIV-positive patients., Methods: Receptor occupancy data from 88 individuals enrolled in two multiple dose trials were included in the population PK-receptor binding model. Out of the 88 individuals, 25 were HIV-1-infected patients and had viral load measurements, whereas the remaining 63 were healthy volunteers. Doses ranged from 3 mg b.i.d. to 600 mg q.d. A previously published PK-PD disease model describing the effect of maraviroc on the viral load was updated by replacing its PD module by the receptor occupancy model. Simulated viral load-time profiles with the updated model were compared with the profiles observed in patients., Results: The majority of measured plasma concentrations were associated with receptor occupancy > or = 50% even at the lowest dose of 3 mg b.i.d. A simple direct E(max) model appeared to describe satisfactorily the PK-receptor occupancy relationship. The estimated K(D) was around 0.0894 ng ml(-1), far below the operational in vivo antiviral IC(50) of 8 ng ml(-1). Accordingly, simulations led to marked overprediction of the decrease in viral load-time profiles., Conclusions: Maraviroc receptor occupancy close to the maximum is required to induce a significant decrease in viral load, indicating that in vivo CCR5 receptor occupancy by maraviroc is not a direct measure of drug inhibitory activity. Considering the imprecision of the measurement in the upper flat part of the maraviroc concentration vs. percent CCR5 occupancy curve, it can reasonably be concluded that routine monitoring of receptor occupancy as a biomarker for maraviroc efficacy will not be helpful. Based on this analysis, it was decided not to use receptor occupancy as a biomarker of viral load inhibition during the development of CCR5 antagonist compounds. more...
- Published
- 2008
- Full Text
- View/download PDF
25. A pharmacokinetic-pharmacodynamic model to optimize the phase IIa development program of maraviroc.
- Author
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Rosario MC, Poland B, Sullivan J, Westby M, and van der Ryst E
- Subjects
- Anti-HIV Agents pharmacology, Cyclohexanes pharmacology, Dose-Response Relationship, Drug, Food, HIV Infections virology, Humans, Maraviroc, Monte Carlo Method, Placebos, RNA, Viral blood, Triazoles pharmacology, Viral Load, Anti-HIV Agents administration & dosage, Anti-HIV Agents pharmacokinetics, Computer Simulation, Cyclohexanes administration & dosage, Cyclohexanes pharmacokinetics, HIV Infections drug therapy, HIV-1 drug effects, Triazoles administration & dosage, Triazoles pharmacokinetics
- Abstract
Objectives: To use a viral dynamics model to compare the effectiveness of in vivo viral inhibition of several doses of maraviroc (MVC;UK-427,857) and to use a modeling approach to support design decisions for a monotherapy study using various dosing regimens of maraviroc given with and without food., Design: The pharmacokinetic-pharmacodynamic model was developed using clinical data from a first monotherapy study (study A4001007). This was a randomized, double-blind, placebo-controlled, multicenter study of maraviroc in 44 asymptomatic HIV-1-infected patients. Patients received maraviroc under food restrictions at 25 mg once daily or 50, 100, or 300 mg twice daily, or placebo for 10 days., Methods: Antiviral responses were assessed by measuring plasma HIV-1 RNA levels during screening, during randomization, at baseline, and daily during the 10 days of treatment and at days 11 to 15, 19, 22, 25, and 40. An integrated pharmacokinetic-pharmacodynamic model was developed using the mixed effects modeling approach with patients' pharmacokinetic profiles on the last day of treatment, HIV-1 RNA levels over time, and the individual viral susceptibility. The parameters derived from the viral dynamic model were used to calculate average viral inhibition fraction, decay rate of actively infected cells, and basic reproductive ratio for each treatment group. Monte Carlo simulation was then used to determine the distribution of viral load change across simulated patients over time for each regimen to be studied in another monotherapy study, A4001015., Results: The decline rate in the 300 mg twice daily group was comparable to that induced by potent protease inhibitor monotherapy, but was significantly slower than that in patients receiving combination therapy including both protease inhibitor and reverse transcriptase inhibitors. The efficacy of inhibition in vivo was estimated to range from 0.15 to 0.38 for the 25 mg once daily dose group and from 0.88 to 0.96 for the 300 mg twice daily dose group., Conclusions: The model has aided the analysis and interpretation of the clinical data. The use of a model-based approach for selecting doses can accelerate drug development by replacing some arms or trials with simulations. more...
- Published
- 2006
- Full Text
- View/download PDF
26. Emergence of CXCR4-using human immunodeficiency virus type 1 (HIV-1) variants in a minority of HIV-1-infected patients following treatment with the CCR5 antagonist maraviroc is from a pretreatment CXCR4-using virus reservoir.
- Author
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Westby M, Lewis M, Whitcomb J, Youle M, Pozniak AL, James IT, Jenkins TM, Perros M, and van der Ryst E
- Subjects
- Anti-HIV Agents therapeutic use, Cell Line, Clone Cells, Cyclohexanes therapeutic use, Evolution, Molecular, Genes, env, Genetic Variation, HIV Envelope Protein gp160 genetics, HIV Infections blood, HIV-1 physiology, Humans, Maraviroc, Phylogeny, Receptors, CCR5 blood, Recombination, Genetic, Triazoles therapeutic use, Anti-HIV Agents pharmacology, CCR5 Receptor Antagonists, Cyclohexanes pharmacology, HIV Infections drug therapy, HIV Infections virology, HIV-1 drug effects, HIV-1 genetics, Receptors, CXCR4 blood, Triazoles pharmacology
- Abstract
Antagonists of the human immunodeficiency virus type 1 (HIV-1) coreceptor, CCR5, are being developed as the first anti-HIV agents acting on a host cell target. We monitored the coreceptor tropism of circulating virus, screened at baseline for coreceptor tropism, in 64 HIV-1-infected patients who received maraviroc (MVC, UK-427,857) as monotherapy for 10 days. Sixty-two patients harbored CCR5-tropic virus at baseline and had a posttreatment phenotype result. Circulating virus remained CCR5 tropic in 60/62 patients, 51 of whom experienced an HIV RNA reduction from baseline of >1 log(10) copies/ml, indicating that CXCR4-using variants were not rapidly selected despite CCR5-specific drug pressure. In two patients, viral load declined during treatment and CXCR4-using virus was detected at day 11. No pretreatment factor predicted the emergence of CXCR4-tropic virus during maraviroc therapy in these two patients. Phylogenetic analysis of envelope (Env) clones from pre- and posttreatment time points indicated that the CXCR4-using variants probably emerged by outgrowth of a pretreatment CXCR4-using reservoir, rather than via coreceptor switch of a CCR5-tropic clone under selection pressure from maraviroc. Phylogenetic analysis was also performed on Env clones from a third patient harboring CXCR4-using virus prior to treatment. This patient was enrolled due to a sample labeling error. Although this patient experienced no overall reduction in viral load in response to treatment, the CCR5-tropic components of the circulating virus did appear to be suppressed while receiving maraviroc as monotherapy. Importantly, in all three patients, circulating virus reverted to predominantly CCR5 tropic following cessation of maraviroc. more...
- Published
- 2006
- Full Text
- View/download PDF
27. Efficacy of short-term monotherapy with maraviroc, a new CCR5 antagonist, in patients infected with HIV-1.
- Author
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Fätkenheuer G, Pozniak AL, Johnson MA, Plettenberg A, Staszewski S, Hoepelman AI, Saag MS, Goebel FD, Rockstroh JK, Dezube BJ, Jenkins TM, Medhurst C, Sullivan JF, Ridgway C, Abel S, James IT, Youle M, and van der Ryst E more...
- Subjects
- Anti-HIV Agents adverse effects, Anti-HIV Agents therapeutic use, Area Under Curve, Cyclohexanes antagonists & inhibitors, Cyclohexanes therapeutic use, Dose-Response Relationship, Drug, HIV Infections blood, HIV Infections virology, Humans, Maraviroc, RNA, Viral blood, Time Factors, Treatment Outcome, Triazoles antagonists & inhibitors, Triazoles therapeutic use, Viral Load statistics & numerical data, Anti-HIV Agents administration & dosage, CCR5 Receptor Antagonists, Clinical Trials, Phase II as Topic, HIV Infections drug therapy, HIV-1 drug effects, Randomized Controlled Trials as Topic
- Abstract
We assessed the efficacy and safety of 10-d monotherapy with the orally administered CCR5 antagonist maraviroc in 63 HIV-1-positive individuals prescreened for the absence of CXCR4-using virus. Maximum reduction in viral load occurred at a median of 10-15 d, with a mean reduction of >or=1.6 log(10) copies/ml at all twice daily doses >or=100 mg. These results provide proof of concept that CCR5 antagonism is a viable antiretroviral therapeutic approach. more...
- Published
- 2005
- Full Text
- View/download PDF
28. Consent for participation in the Bloemfontein vitamin A trial: how informed and voluntary?
- Author
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Joubert G, Steinberg H, van der Ryst E, and Chikobvu P
- Subjects
- Adult, Female, Humans, Pregnancy, South Africa, HIV Infections drug therapy, Infectious Disease Transmission, Vertical prevention & control, Informed Consent, Pregnancy Complications, Infectious drug therapy, Randomized Controlled Trials as Topic, Vitamin A therapeutic use
- Published
- 2003
- Full Text
- View/download PDF
29. Missing or contradictory answers on questionnaires--a valuable source of information.
- Author
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Joubert G, van der Ryst E, Steyn F, and le Roux J
- Subjects
- Female, Humans, Male, South Africa, HIV Infections prevention & control, Health Knowledge, Attitudes, Practice, Surveys and Questionnaires
- Published
- 2001
30. HIV/AIDS-related knowledge, attitudes and practices among South African military recruits.
- Author
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van der Ryst E, Joubert G, Steyn F, Heunis C, le Roux J, and Williamson C
- Subjects
- Adolescent, Adult, Condoms statistics & numerical data, Cross-Sectional Studies, Humans, Male, Sexual Behavior, South Africa, HIV Infections prevention & control, Health Knowledge, Attitudes, Practice, Military Personnel statistics & numerical data
- Abstract
Objectives: To assess the level of HIV-related knowledge, as well as high-risk behaviour and attitudes towards HIV, in a group of South African National Defence Force (SANDF) recruits., Design: Cross-sectional study., Setting: Tempe military base in Bloemfontein., Subjects: Three hundred and thirty-nine recruits from one company., Outcome Measures: HIV-related knowledge, attitudes and practices based on a self-administered questionnaire., Results: All of the recruits were male, and most of them (81.4%) were black. The majority of recruits (98.5%) were between 18 and 24 years old. They had a good level of knowledge regarding HIV and AIDS, with more than 80% giving a correct response in most cases. However, several important misconceptions regarding HIV/AIDS and its transmission still exist. Furthermore, several recruits still practised high-risk behaviour, such as not using condoms with casual or new partners. Most obtained their knowledge regarding HIV/AIDS from schools (34.8%), health and social services (27.1%) and the printed media (17.7%), while only 5.2% stated that they learnt about HIV/AIDS from the SANDF education programmes., Conclusion: Efforts towards initiating behaviour changes in military recruits should be intensified, and if necessary education programmes should be adapted to facilitate achievement of this goal. more...
- Published
- 2001
31. Possible human ehrlichiosis in the Free State.
- Author
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Pretorius AM, Venter TP, van der Ryst E, and Kelly PJ
- Subjects
- Ehrlichiosis physiopathology, Fluorescent Antibody Technique, Indirect, Humans, Male, Middle Aged, Ehrlichia chaffeensis, Ehrlichiosis diagnosis
- Published
- 1999
32. Severe encephalopathies in children with antibodies reactive with Rickettsia africae.
- Author
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Jacquemard R, Pretorius AM, van der Ryst E, Venter A, and Kelly PJ
- Subjects
- Antibodies, Bacterial blood, Child, Child, Preschool, Humans, Rickettsiaceae immunology, Brain Diseases microbiology, Rickettsia Infections diagnosis
- Published
- 1998
33. The use of psychiatric rating scales--a note of caution.
- Author
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van der Ryst E, Joubert G, Strydom W, Scott C, Boshoff W, and Els C
- Subjects
- Comorbidity, HIV Infections psychology, Humans, Reproducibility of Results, Psychiatric Status Rating Scales standards
- Published
- 1998
34. Usefulness of HIV-1 V3 serotyping in studying the HIV-1 epidemic in South Africa.
- Author
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Cheingsong-Popov R, Williamson C, Lister S, Morris L, van Harmelen J, Bredell H, Wood R, Sonnenberg P, van der Ryst E, Martin D, and Weber J
- Subjects
- Disease Outbreaks, Female, HIV Antibodies immunology, HIV Envelope Protein gp120 classification, HIV Infections epidemiology, HIV-1 genetics, Humans, Male, Peptide Fragments classification, Sensitivity and Specificity, South Africa epidemiology, HIV Envelope Protein gp120 immunology, HIV Infections virology, HIV-1 classification, Peptide Fragments immunology, Serotyping
- Published
- 1998
35. More cases of invasive Kaposi's sarcoma?
- Author
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Viljoen JI, van der Ryst E, and Steyn D
- Subjects
- Adult, Female, Humans, Male, AIDS-Related Opportunistic Infections diagnosis, Sarcoma, Kaposi diagnosis, Skin Neoplasms diagnosis
- Published
- 1998
36. Hepatitis D virus--how prevalent?
- Author
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van der Ryst E, Cloete K, van Heerden A, Smit EJ, and Williams MM
- Subjects
- Humans, Prevalence, South Africa epidemiology, Hepatitis D epidemiology
- Published
- 1997
37. Lack of evidence for early cases of HIV seropositivity/AIDS in the Free State region.
- Author
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van der Ryst E, Cloete K, and Opperman L
- Subjects
- Adult, Humans, Male, Retrospective Studies, South Africa epidemiology, Acquired Immunodeficiency Syndrome epidemiology, HIV Seropositivity epidemiology
- Published
- 1997
38. Promoting HIV vaccine research and development in southern Africa.
- Author
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van der Ryst E, Gray C, Williamson C, Morris L, Abdool Karim Q, Hide W, and Esparza J
- Subjects
- Africa, HIV Infections prevention & control, Humans, Research, AIDS Vaccines
- Published
- 1997
39. Challenge of chimpanzees immunized with a recombinant canarypox-HIV-1 virus.
- Author
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Girard M, van der Ryst E, Barré-Sinoussi F, Nara P, Tartaglia J, Paoletti E, Blondeau C, Jennings M, Verrier F, Meignier B, and Fultz PN
- Subjects
- AIDS Vaccines administration & dosage, Animals, Avipoxvirus genetics, HIV Antibodies biosynthesis, HIV Infections immunology, HIV-1 immunology, Immunoenzyme Techniques, Male, Neutralization Tests, Pan troglodytes, Vaccines, Synthetic administration & dosage, Viral Vaccines administration & dosage, AIDS Vaccines immunology, HIV Infections prevention & control, Vaccines, Synthetic immunology, Viral Vaccines immunology
- Abstract
To evaluate the potential protective efficacy of a live recombinant human immunodeficiency virus type 1 (HIV-1) canarypox vaccine candidate, two chimpanzees were immunized five times with ALVAC-HIV-1 vCP250, a recombinant canarypox virus that expresses the HIV-1[IIIB(LAI)] gp120/TM, gag, and protease gene products. One month after the last booster inoculation, the animals were challenged by intravenous injection of cell-associated virus in the form of peripheral blood mononuclear cells from an HIV-1[IIIB(LAI)]-infected chimpanzee. One chimpanzee with a neutralizing antibody titer to HIV-1[IIIB(LAI)] of 128 at the time of challenge was protected, whereas both the second animal, with a neutralizing antibody titer of 32, and a naive control animal became infected. At 5 months after challenge, the protected chimpanzee and a third animal, previously immunized with various HIV-1[MN] antigens, were given a booster inoculation. The two animals were challenged intravenously 5 weeks later with twenty 50% tissue culture infectious doses of cell-free HIV-1[DH12], a heterologous subtype B isolate. Neither chimpanzee had neutralizing antibodies to HIV-1[DH12], and neither one was protected from infection with this isolate. The immune responses elicited by vaccination against HIV-1[IIIB(LAI)] or HIV-1[MN] did not, therefore, protect the animals from challenge with the heterologous cell-free HIV-1[DH12]. more...
- Published
- 1997
- Full Text
- View/download PDF
40. Should South Africa be preparing for HIV-1 vaccine efficacy trials?
- Author
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Morris L, van der Ryst E, Gray C, and Williamson C
- Subjects
- Acquired Immunodeficiency Syndrome epidemiology, Acquired Immunodeficiency Syndrome prevention & control, Animals, Disease Outbreaks, Humans, South Africa epidemiology, AIDS Vaccines, Clinical Trials as Topic, HIV-1 genetics
- Published
- 1997
41. Antibodies to HCV and HTLV-I in a group of HIV-seropositive STD patients.
- Author
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van der Ryst E, Pretorius A, and Smith MS
- Subjects
- Humans, Risk Factors, Antibodies, Viral blood, HIV Seropositivity virology, Hepacivirus isolation & purification, Hepatitis Antibodies blood, Human T-lymphotropic virus 1 isolation & purification
- Published
- 1995
42. Myelopathy in a patient dually infected with HIV-1 and HTLV-I.
- Author
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van der Ryst E and Smith MS
- Subjects
- Adult, Female, Humans, Acquired Immunodeficiency Syndrome complications, Paraparesis, Tropical Spastic complications
- Published
- 1992
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