518 CD4 Activation Predicts Virologic Failure in HAART for Primary HIV F. M. Hecht*1, R. Gascon1, L. Liu1, S. Deeks1, J. Kahn1, M. Chesney1, R. Grant1, M. Busch2, M. McGrath1 1Univ of California at San Francisco and 2Blood Ctrs of the Pacific
Background: The objective of this study was to assess the role of immune activation, after controlling for virologic factors and adherence, in predicting failure of HAART in persons with primary/early HIV infection (P/EHI).
Methods: We assessed persons in the UCSF Options cohort who started HAART within 12 months of HIV seroconversion, took at least 12 weeks of HAART, and had immune activation studies. Treatment failure (TF) was defined as either failure to reach a viral load (VL) < 500 (Bayer, bDNA) by week 24 of treatment or two consecutive VL > 500 after a VL < 500. We defined persons with < 24 weeks of HAART as failures if there was < 1 log decrease by week 12 or an increase of VL > 0.5 log from the nadir value. Treatment success (TS) was defined as having a VL < 500 by week 24 and none of the failure criteria. The mean florescent intensity of CD38 markers on CD4 and CD8 cells was measured using flow cytometry to determine T-cells activation at start of HAART (baseline). Adherence was assessed at each study visit using a self-report measure, and measures were summed over time. Participants were defined as having resistance if there was a primary resistance mutation on genotyping.
Results: There were 11 persons in the TF group and 79 in the TS group. In bivariate analysis, factors associated with TF were: higher baseline CD4 activation (median CD4CD38 50.2 vs 33.1, p = 0.002), higher baseline CD8 activation (median CD8CD38 198.1 vs 91.0.); lower adherence (< 90% in 27% vs 3%, p = 0.02), higher baseline VL (median 240,406 vs 44,628, p = 0.03), higher baseline CD8 count (1071 vs 735, p = 0.03) and lower baseline CD4 count (378 vs 468, p = 0.05). Replication capacity, type of regimen (protease inhibitor or NNRTI based), resistance mutations, and macrophage activation were not associated with TF. In a multivariate model with all significant predictors included, having above the median level of CD4 activation was the strongest predictor of TF (OR 2.3, 95% CI 1.04 to 5.2); adherence was close to the level of significance (OR 6.8, 95% CI 0.84 to 55.6).
Conclusions: CD4 activation prior to starting HAART predicted treatment failure after controlling for VL, CD4 count, and adherence. This suggests that CD4 activation at treatment initiation is important in the pathogenesis of treatment failure in P/EHI. Treatment strategies that decrease activation or enhance virologic suppression may be useful in persons with P/EHI and high CD4 activation.
