Maraviroc is able to inhibit dual-R5 viruses in a dual/mixed HIV-1-infected patient
| Autor: | Monique Nijhuis, Petra M. van Ham, Steven F. L. van Lelyveld, Dorien de Jong, Jori Symons, Andy I. M. Hoepelman, Annemarie M. J. Wensing |
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| Rok vydání: | 2011 |
| Předmět: |
Male
Microbiology (medical) Chemokine Genotype Anti-HIV Agents viruses Population HIV Infections CCR5 receptor antagonist Biology Virus Cell Line Maraviroc chemistry.chemical_compound Cyclohexanes Humans Pharmacology (medical) education Tropism Pharmacology education.field_of_study virus diseases Middle Aged Triazoles Virology Viral Tropism Treatment Outcome Infectious Diseases Viral replication chemistry HIV-1 biology.protein Viral disease |
| Zdroj: | Journal of Antimicrobial Chemotherapy. 66:890-895 |
| ISSN: | 1460-2091 0305-7453 |
| Popis: | Objectives: Maraviroc is the first licensed chemokine co-receptor 5 (CCR5) co-receptor antagonist in clinical practice. It is currently being used in patients harbouring exclusively CCR5-tropic virus. The objective of the study was to investigate the impact of maraviroc on viruses with different co-receptor preferences in a patient with a dual/mixed (D/M) infection. Methods: We present a case report of an HIV-1 patient infected with a D/M virus population. Co-receptor tropism was determined by phenotypic and genotypic tests. Biological clones from pre- and post-maraviroc therapy were generated. Tropism of these infectious clones was investigated in U373-MAGI cells expressing CD4+CCR5+ or CD4+CXCR4+. Maraviroc susceptibility and viral replication were determined using donor peripheral blood mononuclear cells (PBMCs). Results: In-depth clonal genotypic analysis revealed the presence of both R5-tropic variants and X4-tropic viruses before the start of maraviroc. During maraviroc therapy all R5-predicted viruses were suppressed. Phenotypic analyses revealed that all biological clones before maraviroc therapy could infect both CCR5- and CXCR4-bearing U373-MAGI cells, demonstrating dual tropism. The baseline biological clones preferentially infected the CCR5 cell line and were fully susceptible to maraviroc in PBMCs (dual-R5). In contrast, during maraviroc therapy the dual-R5-tropic viruses were replaced by more X4-tropic viruses (dual-X4), which could not be inhibited by maraviroc. Conclusions: This case report demonstrates that dual-tropic viruses, capable of using both co-receptors in phenotypic assays, can be inhibited by maraviroc if they have a CCR5 co-receptor preference in vivo. |
| Databáze: | OpenAIRE |
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