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

Curr HIV Res. 2012 Oct;10(7):597-605. doi: 10.2174/157016212803306032.

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-na�ve 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-naive 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-ribosyl Cyclase 1 / immunology
  • Adult
  • Anti-HIV Agents / pharmacology*
  • Antiretroviral Therapy, Highly Active*
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • HIV Seropositivity / drug therapy
  • HIV Seropositivity / immunology*
  • HIV Seropositivity / physiopathology
  • HIV-1 / immunology*
  • Humans
  • Immune Reconstitution Inflammatory Syndrome / virology*
  • Immunologic Memory
  • Interleukin-7 Receptor alpha Subunit / immunology
  • Lopinavir / pharmacology*
  • Lymphocyte Activation / immunology*
  • Male
  • Middle Aged
  • Pilot Projects
  • Prospective Studies
  • Ritonavir / pharmacology*
  • T-Lymphocytes / immunology*
  • Viral Load / drug effects

Substances

  • Anti-HIV Agents
  • Interleukin-7 Receptor alpha Subunit
  • Lopinavir
  • ADP-ribosyl Cyclase 1
  • Ritonavir