352 Protease Inhibitor-containing HAART is Associated with Decreased In Vivo T-cell Activation Independent of its Effects on Viral Replication P. Hunt*, J. Martin, D. Bangsberg, A. Moss, E. Sinclair, B. Bredt, S. Deeks Univ of California at San Francisco
Background: A reduction in T-cell activation may mediate the immunologic benefit of HAART in HIV-infected patients (pts), even among those with sub-optimal virologic responses. While protease inhibitors (PI) directly inhibit activation-induced T-cell apoptosis in vitro, it is unknown whether PI-based HAART decreases in vivo T-cell activation in HIV-infected pts, independently of its effect on viral replication.
Methods: Untreated and HAART-treated HIV-infected pts were sampled from one clinic-based cohort (SCOPE) and one community-based cohort (REACH) in San Francisco. The percentages of activated (CD38+/HLA-DR+) CD4+ and CD8+ T-cells were measured by flow cytometry and log10 transformed to meet linear regression model assumptions.
Results: Of the 188 pts evaluated, 13 were untreated, 139 were being treated with PI-containing HAART, and 36 were being treated with PI-sparing HAART. Median values were: age, 45 yrs; nadir CD4+ T-cell count, 142 cells/mm3; and current CD4+ T-cell count, 372 cells/mm3. The 99 pts with detectable plasma HIV RNA levels on the day of flow cytometry had a median of 7% activated CD4+ T-cells and 21% activated CD8+ T-cells. Among these, HAART-treated pts had a mean of 0.2 log10% less activated CD4+ T-cells (p = 0.06) and 0.2 log10% less activated CD8+ T-cells (p = 0.01) than untreated pts, after adjustment for plasma HIV RNA levels, nadir CD4+ T-cell count, and hepatitis C serostatus. Among treated pts with detectable viremia, T-cell activation was similar among those receiving PI-containing and PI-sparing regimens. The 89 HAART-treated pts with undetectable plasma HIV RNA levels had a median of 4% activated CD4+ T-cells and 8% activated CD8+ T-cells. Among these, pts on PI-containing regimens had a mean of 0.14 log10% fewer activated CD4+ T-cells (p = 0.06) than those on PI-sparing regimens, but similar levels of activated CD8+ T-cells (p = 0.95), after adjustment for nadir CD4+ T-cell count, hepatitis C serostatus, and time maintaining plasma HIV RNA levels = 1000 copies/ml.
Conclusions: HAART-treated pts with detectable viremia have less T-cell activation than untreated pts, independent of the level of viral replication. Among pts with undetectable viremia, PI-based HAART is associated with less CD4+ T-cell activation than PI-sparing HAART, suggesting a direct PI suppressive effect on in vivo T-cell activation.
