Immunological and virological features of HIV-infected patients with increasing CD4 cell numbers despite virological failure during protease inhibitor-based therapy.

Abstract

To investigate the extent of functional T cell recovery and to characterize plasma virus and virus producing cells in patients with increasing CD4 cell counts despite virological failure during protease inhibitor (PI) based therapy. The study group included 13 patients who were treated for at least 12 months with a PI based regimen and were selected on the basis of a sustained immunological response (increase of > 70 CD4 cells/microL) despite virological failure (< 1 log10 copies/mL decrease in HIV-1 RNA plasma levels). Compared to a historical series of 11 complete responders with less advanced disease, the proportion of memory CD4 T cells was significantly higher (67.8+/-17.8 vs. 52.8+/-11.0; P=0.045) and the proportion of naive CD4 T cells significantly lower (30.5+/-14.8 vs. 45.0+/-10.4, P=0.021) in patients who were immunological responders/virological nonresponders. In those patients, ongoing viral replication was associated with a strong activation of circulating CD8 T lymphocytes; interleukin-2 production remained decreased. CD4 T cell reactivity to cytomegalovirus proteins was observed in nine of 11 patients tested. In the study group, the proportion of infectious virus present in plasma as well as the levels of intracellular viral replication were similar to those measured in untreated patients. Virological failure in this group of patients probably resulted from pre-existing mutations in the reverse transcriptase gene. This study of patients with increasing CD4 cell numbers despite virological failure shows the persistence of immune activation and partial immune restoration with no evidence of specific viral dynamics in vivo.