TY - JOUR
T1 - Effect of raltegravir on the total and unintegrated proviral HIV DNA during raltegravir-based HAART
AU - Nicastri, Emanuele
AU - Tommasi, Chiara
AU - Abbate, Isabella
AU - Bonora, Stefano
AU - Tempestilli, Massimo
AU - Bellagamba, Rita
AU - Viscione, Magdalena
AU - Rozera, Gabriella
AU - Gallo, Anna L.
AU - Ivanovic, Jelena
AU - Amendola, Alessandra
AU - Pucillo, Leopoldo
AU - Di Perri, Giovanni
AU - Capobianchi, Maria R.
AU - Narciso, Pasquale
PY - 2011
Y1 - 2011
N2 - 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 (C trough) was measured by HPLC-ultraviolet and patients were divided into two groups according to the median raltegravir C trough. 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/mm 3, and 2,668 ±4,721 copies/10 6 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 trough and classical virological parameters was observed. Nevertheless, the decay of proviral HIV DNA was more pronounced in patients displaying C troughtrough>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.
AB - 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 (C trough) was measured by HPLC-ultraviolet and patients were divided into two groups according to the median raltegravir C trough. 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/mm 3, and 2,668 ±4,721 copies/10 6 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 trough and classical virological parameters was observed. Nevertheless, the decay of proviral HIV DNA was more pronounced in patients displaying C troughtrough>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.
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U2 - 10.3851/IMP1833
DO - 10.3851/IMP1833
M3 - Article
C2 - 21900711
AN - SCOPUS:80052946068
VL - 16
SP - 797
EP - 803
JO - Antiviral Therapy
JF - Antiviral Therapy
SN - 1359-6535
IS - 6
ER -