Changes in host cell molecules acquired by circulating HIV-1 in patients treated with highly active antiretroviral therapy and interleukin-2

Objective: To analyse cell membrane proteins (CMP) acquired by HIV-1 presen t in the plasma of asymptomatic patients, and their modifications after a c ycle of highly active antiretroviral therapy (HAART) and interleukin (IL)-2 . Design and methods: Plasma samples from eight drug-naive asymptomatic subje cts underwent immobilized antibody capture (IAC) to detect CMP on the surfa ce of circulating HIV-1. The CMP considered were lymphocyte subset markers (CD45RA, CD45RO), activation markers (HLA-DR), adhesion molecules (LFA3), c ostimulatory proteins (B7-2), lymph-node homing receptors (CD62L) and pro-a poptosis molecules (FasL). This analysis was repeated after one cycle of HA ART+IL-2, after virus rebound. Results: LFA3, followed by CD45RO and HLA-DR, are the most represented CMP on the surface of circulating virions in naive asymptomatic patients; CD45R A, CD62L, B7-2 and FasL are detected only occasionally After rebound, a sig nificant reduction of CD45RO and HLA-DR, but not of LFA-3, is observed on v irions, whereas CD45RA and CD62L, as well as other molecules, are not affec ted, remaining almost undetectable. Conclusions: Assuming that CMP on HIV-1 reflect the cellular origin of viri ons, activated T cells expressing CD45RO, HLA-DR, and LFA-3 may be the main source of HIV-1 in asymptomatic patients. After a cycle of HAART+IL-2, fol lowed by therapy interruption, CD45RA and CD62L are detected on virions rar ely, indicating that even during virus rebound, expanded naive T cells do n ot become a major target of virus replication. Furthermore, the presence of HLA-DR on rebound HIV-1 is decreased, consistent with decreased activation of the HIV-producing cells. More extensive investigation may clarify the s ignificance of these findings with respect to pathogenesis. (C) 2001 Lippin cott Williams & Wilkins.