Background: We aimed to assess the impact of TDF/FTC +LPV/r-based HAART on the quality of immune reconstitution and on microbial translocation (MT) in HIV-infected antiretroviral-naïve late presenting patients. Methods: 40 HIV+ antiretroviral-naive patients starting a first TDF/FTC+LPV/r HAART with CD4+≤350 cell/µL (20 �severe immune depression patients -SID CD4+≤100/µL; 20 moderate immune depression patients MID, CD4+ 200-350/µL) were followed for 12 months (T12). CD38+CD8+, CD4+5R0+CD38+CD8+, CD95+CD4+/CD8+, CD127+CD4+/CD8+, pStat5 signalling (flow cytometry), plasma IL-7, sCD14 (ELISA), LPS (LAL) were tested at T0 and T12. Results: By T12, both study groups displayed significant CD4+ increase and HIV-RNA reduction (p<.01). Despite similar CD38+CD8+ reduction in both SID (p=.039) and MID (p=.007), SID displayed a significant rise in CD45R0+CD38+CD8+ (p=.039). MID displayed significant increase of CD95+CD4+ (p=.002), with higher baseline and T12 levels (p=.024; p=.002), suggesting reduced commitment to apoptosis. At T12, different IL-7/IL-7R profile was shown according to pre-therapy immune depression. As compared to SID, MID increased circulating IL-7 (p=.049) displaying higher baseline and T12 CD127+CD4+ (p=.0001; p=.004) and CD127+CD8+ (p=.006; p=.009). By T12, only MID displayed significant reduction in LPS (p=.020) and sCD14 (p=.005). Conclusions: In antiretroviral-naïve late presenters, we show different immune reconstitution quality and MT upon 12 months TDF/FTC+LPV/r-containing HAART according to the severity of pre-therapy immune depression. Despite equal T-cell activation decline, only MID patients tend to reduce pro-apoptotic T-lymphocytes, with a gain in circulating IL-7 and higher CD127+ central-memory T-cells, and a possible control over MT.

Immune reconstitution in HIV+ subjects on Lopinavir/Ritonavir-based HAART according to the severity of pre-therapy CD4+ / G. Marchetti, E. Merlini, E. Sinigaglia, N. Iannotti, F. Bai, A. Savoldi, C. Tincati, G. Carpani, T. Bini, A. d'Arminio Monforte. - In: CURRENT HIV RESEARCH. - ISSN 1570-162X. - 10:7(2012 Oct), pp. 597-605. [10.2174/157016212803306032]

Immune reconstitution in HIV+ subjects on Lopinavir/Ritonavir-based HAART according to the severity of pre-therapy CD4+

G. Marchetti;E. Merlini;F. Bai;A. Savoldi;C. Tincati;A. d'Arminio Monforte
2012

Abstract

Background: We aimed to assess the impact of TDF/FTC +LPV/r-based HAART on the quality of immune reconstitution and on microbial translocation (MT) in HIV-infected antiretroviral-naïve late presenting patients. Methods: 40 HIV+ antiretroviral-naive patients starting a first TDF/FTC+LPV/r HAART with CD4+≤350 cell/µL (20 �severe immune depression patients -SID CD4+≤100/µL; 20 moderate immune depression patients MID, CD4+ 200-350/µL) were followed for 12 months (T12). CD38+CD8+, CD4+5R0+CD38+CD8+, CD95+CD4+/CD8+, CD127+CD4+/CD8+, pStat5 signalling (flow cytometry), plasma IL-7, sCD14 (ELISA), LPS (LAL) were tested at T0 and T12. Results: By T12, both study groups displayed significant CD4+ increase and HIV-RNA reduction (p<.01). Despite similar CD38+CD8+ reduction in both SID (p=.039) and MID (p=.007), SID displayed a significant rise in CD45R0+CD38+CD8+ (p=.039). MID displayed significant increase of CD95+CD4+ (p=.002), with higher baseline and T12 levels (p=.024; p=.002), suggesting reduced commitment to apoptosis. At T12, different IL-7/IL-7R profile was shown according to pre-therapy immune depression. As compared to SID, MID increased circulating IL-7 (p=.049) displaying higher baseline and T12 CD127+CD4+ (p=.0001; p=.004) and CD127+CD8+ (p=.006; p=.009). By T12, only MID displayed significant reduction in LPS (p=.020) and sCD14 (p=.005). Conclusions: In antiretroviral-naïve late presenters, we show different immune reconstitution quality and MT upon 12 months TDF/FTC+LPV/r-containing HAART according to the severity of pre-therapy immune depression. Despite equal T-cell activation decline, only MID patients tend to reduce pro-apoptotic T-lymphocytes, with a gain in circulating IL-7 and higher CD127+ central-memory T-cells, and a possible control over MT.
HAART; immune depression; immune reconstitution; late presenter; microbial translocation; T-cell activation
Settore MED/17 - Malattie Infettive
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/193185
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