Immune reconstitution in HIV+ subjects on lopinavir/ritonavir-based HAART according to the severity of pre-therapy CD4+.
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.
Dept of Medicine, Surgery and Dentistry- Clinic of Infectious Diseases - "San Paolo" Hospital - University of Milan, Milan, Italy. giulia.marchetti@unimi.it
Giulia
G
Marchetti
Esther
E
Merlini
Elisabetta
E
Sinigaglia
Nathalie
N
Iannotti
Francesca
F
Bai
Alessia
A
Savoldi
Camilla
C
Tincati
Giovanni
G
Carpani
Teresa
T
Bini
Antonella
A
Arminio Monforte
D051997:ADP-ribosyl Cyclase 1 / Q000276:immunology; D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006679:HIV Seropositivity / Q000188:drug therapy / Q000276:immunology* / Q000503:physiopathology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D054019:Immune Reconstitution Inflammatory Syndrome / Q000821:virology*; D007156:Immunologic Memory; D053699:Interleukin-7 Receptor alpha Subunit / Q000276:immunology; D061466:Lopinavir / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D019438:Ritonavir / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000276:immunology*; D019562:Viral Load / Q000187:drug effects
D019380:Anti-HIV Agents; D053699:Interleukin-7 Receptor alpha Subunit; D061466:Lopinavir; D051997:ADP-ribosyl Cyclase 1; D019438:Ritonavir