CD4 increases in immunological non-responders despite suppressive therapy following switch to nuke-sparing regimen of ATZ/SQV/r

3 September 2007. Related: Conference reports, Treatment strategies, IAS 4th Sydney 2007.

Simon Collins, HIV i-Base

Gerd Fätkenheuer and colleagues from University Hospital, Infectious Diseases, Cologne, presented a poster on CD4 recovery in 15 patients (11 men, 4 women) who switched to an RTI-sparing combination, after not achieving immunological benefit (CD4 remained <250 cells/mm³) despite undetectable viral load for over 6 months. Original therapy was lopinavir/r (n=10), nelfinavir (n=1), efavirenz (n=1); background nucleosides were AZT/3TC (n=10), AZT/abacavir (n=1) and AZT/tenofovir (n=3).

Patients were switched to atazanavir (ATV, 300 mg QD), saquinavir (SQV, 1000 mg BID) and ritonavir (RTV, 100 mg QD) and followed for 48 weeks. T cell activation (CD38+HLA-DR+) on CD4+ and CD8+ T- cells were longitudinally (0, 24 and 48 weeks) determined and compared to good immunologic (IgR) responders with ART (n=10) and patients with high CD4+ T cells without ART (n=9).

Baseline characteristics included median [IQR] CD4 count 197 cells/mm³ [130-220]; months on ART 20 [6-114]; and age 46 years [38-62].

Median CD4 cell count (and CD4 percentage) improved significantly to 230 cells/mm³ (14%), [170-290, 10-17%] and 260 cells/mm³ 17% [195-415, 13.5-18.5%] at weeks 24 and 48 respectively. Only one patient discontinued the study. Viral load remained < 50 copies/mL in the remaining 14 patients.

Activation markers did not change longitudinally or in comparison to IgR. Subjects with detectable HIV-RNA and high CD4+ T- cells demonstrated higher expression of CD38 on CD4+ and CD8+ T cells and HLA-DR on CD8+ T cells (p<0.05).

Comment

Although this is small, uncontrolled study, in patients who fail to show a CD4 response on recommended first-line regimens, this option may deserve further exploration.

In the symposium on HIV pathogenesis on the first day of the conference, Michael Lederman referenced a study showing that up to 20% patients fail to achieve CD4 increase to greater than 350 cells/mm3 after five years of suppressive therapy (below 95th percentile of HIV negative population). [2]

References:

1. Lehmann C, Hofmann A, Fätkenheuer G et al. Recovery of CD4+ T cells after switch to a nucleoside free regimen in patients with poor immunologic response despite complete HIV-RNA suppression. 4th IAS conference, Sydney, 2007. Abstract WEPEB043.
   http://www.ias2007.org/pag/Abstracts.aspx?AID=1834
2. Lederman M. How HIV makes you sick: mechanisms of CD4+ T cell loss and recovery. 4th IAS conference, Sydney, 2007. Abstract MOPL102.
   http://www.ias2007.org/pag/PSession.aspx?s=22