Effect of raltegravir on the total and unintegrated proviral HIV DNA during raltegravir-based HAART

Autor: Isabella Abbate, Alessandra Amendola, Maria Rosaria Capobianchi, Pasquale Narciso, Leopoldo Paolo Pucillo, Anna Loredana Gallo, Magdalena Viscione, Giovanni Di Perri, Gabriella Rozera, Jelena Ivanovic, Chiara Tommasi, Emanuele Nicastri, Stefano Bonora, Rita Bellagamba, Massimo Tempestilli
Rok vydání: 2011
Předmět:
Adult
Male
Anti-HIV Agents
Virus Integration
Mononuclear
Human immunodeficiency virus (HIV)
Antiretroviral Therapy
HIV Infections
Biology
medicine.disease_cause
Genome
Proviruses
Antiretroviral Therapy
Highly Active
Raltegravir Potassium
medicine
Leukocytes
Humans
Pharmacology (medical)
Highly Active
Pharmacology
drug effects/genetics
Middle Aged
Viral Load
Raltegravir
Virology
Pyrrolidinones
drug therapy/virology
virology
CD4 Lymphocyte Count
Infectious Diseases
Adult
Anti-HIV Agents
therapeutic use
Antiretroviral Therapy
Highly Active
CD4 Lymphocyte Count
Female
HIV Infections
drug therapy/virology
HIV-1
drug effects/genetics
Humans
Leukocytes
virology
Male
Middle Aged
Proviruses
drug effects/genetics
Pyrrolidinones
therapeutic use
Viral Load
Virus Integration
therapeutic use
Plasma concentration
HIV-1
Leukocytes
Mononuclear
Female
medicine.drug
Zdroj: Antiviral therapy. 16(6)
ISSN: 2040-2058
Popis: Background Raltegravir is the first approved antiretroviral able to prevent HIV genome integration into the host chromosomes. The aim of the study is to test if raltegravir plasma concentrations can be associated with proviral DNA decline during raltegravir-based salvage therapy. Methods A total of 33 multidrug-resistant HIV-infected patients were enrolled in a longitudinal open-label pilot study and completed a 24-week follow-up. The CD4+ T-cell count, plasma viral load, proviral HIV DNA and two-long-terminal repeat (2-LTR) circular forms were assessed at baseline, day 14, 30, 60, 90 and 180. The raltegravir trough concentration (Ctrough) was measured by HPLC-ultraviolet and patients were divided into two groups according to the median raltegravir Ctrough. Results The mean ±sd values of baseline HIV RNA, CD4+ T-cell count and HIV DNA were 4.4 ±0.82 log copies/ml, 256 ±177 cells/mm3, and 2,668 ±4,721 copies/106 peripheral blood mononuclear cells, respectively. Despite a transient increase of total DNA at week 2, a marked proviral DNA decay ( P=0.01) with an increase of the 2-LTR unintegrated/total DNA ratio ( P=0.06) over time was observed. At univariate analysis, no correlation between raltegravir C and trough classical virological parameters was observed. Nevertheless, the decay of proviral HIV DNA was more pronounced in patients displaying Ctrough trough>158 ng/ml ( P=0.046). Conclusions Successful raltegravir-based therapy produces a significant decline in proviral DNA and is associated with an increase of the unintegrated/total DNA ratio. Further studies are necessary to define the possible role of pharmacokinetic raltegravir monitoring and the biological meaning of unintegrated proviral DNA.
Databáze: OpenAIRE
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