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.
