Impact of HIV-1 replication on immunological evolution during long-term dual-boosted protease inhibitor therapy
| Autor: | Valentin Bartha, G Knecht, Peter Gute, Nils von Hentig, Pavel Khaykin, H. R. Brodt, Christoph Stephan, Markus Bickel, Annemarie Berger, Martin Stürmer, Eva Herrmann |
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| Rok vydání: | 2012 |
| Předmět: |
Adult
Male Microbiology (medical) Anti-HIV Agents Human Immunodeficiency Virus Proteins Immunology Salvage therapy HIV Infections Biology Virus Replication Risk Factors Drug Resistance Viral medicine Humans Immunology and Allergy Protease inhibitor (pharmacology) Treatment Failure Aged virus diseases Lopinavir HIV Protease Inhibitors General Medicine Middle Aged Viral Load Virology CD4 Lymphocyte Count Atazanavir Treatment Outcome Viral evolution Mutation HIV-1 Female Ritonavir Viral load Saquinavir medicine.drug |
| Zdroj: | Medical Microbiology and Immunology. 202:117-124 |
| ISSN: | 1432-1831 0300-8584 |
| DOI: | 10.1007/s00430-012-0276-8 |
| Popis: | To explore CD4-cell and viral evolution in relation to different levels of HIV-1 replication, as observed during protease inhibitor (PI)-based antiretroviral therapy. Adult HIV-1 infected cohort patients, receiving historical salvage therapy with daily doses of saquinavir (2,000 mg), ritonavir (200 mg) and either lopinavir (800 mg) or atazanavir (300 mg) for36 weeks were retrospectively analysed for highest detectable viral load up to week 96 and assigned to groups according to the viral load level: always50 copies/ml (1), 50-199 copies/ml (2), 200-499 copies/ml (3) and ≥500 copies/ml (4). A total of 126 patients were evaluated; at baseline, median CD4-cell count was 204/mm(3), HIV-1 RNA was 5.13 Log10-copies/ml and duration of prior HIV-1 infection was 11.7 years. Patients were assigned by 43, 30, 7 and 20 % to groups 1-4. Median observation time was 136 weeks (range: 38-304); at weeks 48/96, the CD4-cell gains for groups 1-4 were +88/+209, +209/+349, +67/+300 and +114.5/+ 128, respectively. After fitting data in a linear fixed effect model, ascending CD4 slopes were continuously increasing for group 1, similarly for 2 and clearly decreasing for 3-4 (p = 0.0006). Of 25 individuals from group 4, patient number with major IAS-USA protease mutations increased from 5 to 10 before and after failing PI therapy, whereas minor mutations remained stable (n = 18). On double-boosted PI therapy, CD4-cell increases through week 96 were similar for patients at always undetectable or with detection of low viral load. Viral detection200 copies/ml was associated with decreasing CD4-cell slopes and emergence of major mutations, supporting this as benchmark for virological failure definition on PI therapy. |
| Databáze: | OpenAIRE |
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