786 CMV-specific IFNgamma Production Correlates with Protection against CMV Reactivation in HIV-infected Patients on HAART A. Weinberg*1, D. A. Wohl2, S. M. Whinney1, R. J. Barrett1, D. G. Brown1, N. Glomb2, C. Van der Horst2 1Univ of Colorado Hlth Sci Ctr, Denver and 2Univ of North Carolina, Chapel Hill
Background: HAART produces potent suppression of HIV replication, elevates CD4 numbers, and decreases opportunistic infections, including CMV. Nevertheless, CMV end-organ disease has been reported in HAART recipients. To understand the predictors of CMV reactivation in patients (pts) on HAART, we prospectively studied CMV cell-mediated immunity (CMI) in CMV-infected AIDS pts on HAART.
Methods: The study enrolled CMV-seropositive pts with AIDS who did not receive CMV prophylaxis. Blood, obtained at clinic visits, was used for in vitro measurements of CMV CMI (lymphocyte proliferation, IFNgamma, IL2, and IL10 production), CMV viral load (VL), CD4 cells, and HIV VL. A logistic-normal model with binomial data was used to analyze binary outcome data with repeated observations.
Results: We obtained 299 blood samples between 6-1997 and 2-2001 from 52 AIDS pts (median pre-HAART CD4 number of 15 cells/µl; range of < 10; 154). Pts received HAART for 0 to 64 months (median =16 mos) during the study and their median CD4 number increased to 150 cells/µl (range of < 10; 799). HIV VL varied from < 1.2 to > 5.9 log10 RNA copies/ml (median = 3.8). There were 40 episodes of CMV reactivation defined by positive CMV VL. CD4 number, CMV lymphocyte proliferation, IL2, and IL10 production did not achieve statistical significance as predictors of CMV reactivation. The risk of CMV reactivation significantly decreased with higher CMV-specific IFNgamma production (OR = 0.03; p = 0.04) and longer HAART duration (OR = 0.5; p = 0.02 for every 6 mos of HAART). Lower HIV VL also showed a trend to decrease the risk of CMV reactivation (OR = 0.5; p = 0.07 for every decrease = 1 log10 HIV RNA copies/ml).
Conclusions: CMV-specific IFNgamma has a unique value as an immunologic predictor of CMV reactivation, demonstrating the importance of CMI in the control of CMV replication in HAART recipients.
