Background: ABT-378/r (LOPINAVIR/r) is a novel HIV protease inhibitor that has shown significant antiviral activity and tolerability in clinical trials. Recent work in vivo has shown that ABT-378/r plus stavudine and lamivudine is highly effective on reducing viral replication and increasing CD4+ T cell numbers in treatment naïve HIV-1 infected patients.
Objective: The aim of this study was to determine the alteration of lymphocyte subpopulations assessing the antiviral effects of ABT-378/r in treatment experienced HIV-1 infected patients.
Design: The study carried out in 17 patients on treatment with HAART and failure. The second line treatment consisted of two RTIS plus KALETRA (GROUP 1) and two RTIS plus PI (GROUP2). Lymphocyte subpopulations were estimated with 3-colour flow cytometry (FACScalibur) at baseline and the end of fourth week (MoAbs : BD).
| Lymph Sub |
Baseline mean (SE) |
Day 30 mean (SE) |
P |
| GROUP1: Viral load |
4.23 (0.39) |
2.83 (0.31) |
0.005 |
| CD4 (abs no) |
289 (108) |
486 (156) |
0.016 |
| % CD45RA+CD62L+ on CD4 |
16.5 (7.0) |
26.8 (6.9) |
0.007 |
| % CD45RO+ on CD4 |
61.5 (5.9) |
58.0 (6.0) |
0.288 |
| % CD38+ on CD8 |
79.2 (5.7) |
75.1 (4.8) |
0.212 |
| % CD38+DR+ on CD8 |
47.5 (4.8) |
44.0 (5.7) |
0.158 |
| GROUP2: Viral load |
5.03 (0.26) |
2.86 (0.45) |
0.0001 |
| CD4 (abs no) |
212 (43) |
299 (53) |
0.038 |
| % CD45RA+CD62L+ on CD4 |
23.4 (4.8) |
24.9 (4.9) |
0.695 |
| % CD45RO+ on CD4 |
61.7 (4.4) |
58.1 (5.1) |
0.083 |
| % CD38+ on CD8 |
75.7 (5.1) |
75.8 (4.8) |
0.966 |
| % CD38+DR+ on CD8 |
39.6 (5.9) |
39.7 (4.8) |
0.979 |
Results: In GROUP1 there was: a) a significant increase in CD4 cell counts and CD4+CD45RA+CD62L+ subpopulations b) a non significant decrease in activation markers on CD8+ cells.
Conclusions: The early increase of “naïve” CD4 seen in GROUP1 is in sharp contrast with GROUP2; were “naïve” CD4 elevation is a later event. More studies are needed to assess whether this finding is a redistribution phenomenon or an early sign of immune reconstitution.
|
