AEGiS-13IAC: The effect of protease inhibitor (PI) and non-pi-based HAART on immune reconstitution.

13th International AIDS Conference

Durban, South Africa - July 9-July 14, 2000

The effect of protease inhibitor (PI) and non-pi-based HAART on immune reconstitution.

Int Conf AIDS 2000 Jul 9-14; 13:(abstract no. TuOrA287)

Smith K, Steffens C, Truckenbrod A, Landay A, Russert M, Al-Harthi L
K. Smith, Rush Presbyterian St. Luke's Medical Center, 600 S. Paulina Suite 143, Chicago, IL, 60612, United States, Tel.: +1 312 942 20 51, Fax: +1 312-942-82-00, E-mail: ksmith2@rush.edu

OBJECTIVE: To examine the impact of PI Vs non-PI regimens on immune reconstitution, we examined T-lymphocyte subsets, activation markers, thymic size and output in HIV+ pts with VL>50. We also compared thymic output between HIV+ pts and HIV- age-matched controls. Methods. T lymphocyte subsets and activation status were evaluated by staining for naive (CD45RA+CD62L+) and memory (CD45RO+CD45RA-) markers on CD4+ T cells and activation (HLA-DR+CD38+) markers on CD4+ and CD8+ T cells using flow cytometric analysis. Thymic output was evaluated by measuring T cell receptor excision circles (TREC) from total PBMCs, CD4+ T cells, and CD8+ T cells. Thymic size was determined using thymic CT scans.

RESULTS: Fifteen HIV+ pts aged 25-40 with VL>50 for >6 months pre-study entry were included. Eight subjects were on PI HAART and 7 subjects were on non-PI HAART. No significant difference was observed between PI and non-PI subgroups in naive CD4+ T cells, in frequency of TRECs in total PBMCs, CD4+ T cells, or CD8+ T cells. We also did not observe a significant difference in thymic size among the two groups. There was no significant difference in activated CD4+ cells between the groups. However, the PI group had a significantly lower percentage of activated CD8+ T cells than the non-PI group (23.6% Vs 35.4%, p = 0.042). Notably, we observed a significantly higher frequency of TRECs in the CD4+ T cell compartment among HIV+ pts, regardless of treatment regimen, than in age-matched HIV-donors (p = 0.001).

CONCLUSIONS: Preliminary analysis suggests that there is no significant difference in thymic size or thymic output observed following PI Vs. non-PI HAART. The decreased activated CD8+ cells in the PI group may suggest an additional effect of PI's on immune activation that is independent of their antiviral effect. Finally, our data demonstrate enhanced thymic output in HAART treated HIV+ pts, which may provide a compensatory mechanism for HIV-mediated T cell depletion.

Keywords: AEGIS, Antiretroviral Therapy, Highly Active, CD4-Positive T-Lymphocytes, Thymus Gland, HIV Infections, CD8-Positive T-Lymphocytes, T-Lymphocyte Subsets, T-Lymphocytes, Protease Inhibitors, Antigens, CD8, Antigens, CD45, Receptors, Antigen, T-Cell, Antigens, CD4, ADP-ribosyl Cyclase, Antigens, CD, Case-Control Studies, CD38 antigen, Human, immunology
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TuOrA287