1. Effect of raltegravir on the total and unintegrated proviral HIV DNA during raltegravir-based HAART
- Author
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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, and Massimo Tempestilli
- Subjects
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 - Abstract
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.
- Published
- 2011