Immune Reconstitution in HIV+ Subjects on Lopinavir/Ritonavir-Based HAART According to the Severity of Pre-Therapy CD4+

Title:Immune Reconstitution in HIV+ Subjects on Lopinavir/Ritonavir-Based HAART According to the Severity of Pre-Therapy CD4+

Volume: 10 Issue: 7

Author(s): Giulia Marchetti, Esther Merlini, Elisabetta Sinigaglia, Nathalie Iannotti, Francesca Bai, Alessia Savoldi, Camilla Tincati, Giovanni Carpani, Teresa Bini and Antonella d’Arminio Monforte

Affiliation:

Keywords: HAART, immune depression, immune reconstitution, late presenter, microbial translocation, T-cell activation

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+, CD45R0+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.

Cite this article as:

Marchetti Giulia, Merlini Esther, Sinigaglia Elisabetta, Iannotti Nathalie, Bai Francesca, Savoldi Alessia, Tincati Camilla, Carpani Giovanni, Bini Teresa and d’Arminio Monforte Antonella, Immune Reconstitution in HIV+ Subjects on Lopinavir/Ritonavir-Based HAART According to the Severity of Pre-Therapy CD4+, Current HIV Research 2012; 10 (7) . https://dx.doi.org/10.2174/157016212803306032