Cellular restoration in HIV infected persons treated with abacavir and a protease inhibitor: age inversely predicts naive CD4 cell count increase

Objective: To characterize early and later indices of cellular restoration among HIV-1 infected persons treated with abacavir and one protease inhibit or and to identify predictors of CD4 cell increases. Methods: Flow-cytometric analyses of lymphocyte phenotypes among 71 antiret roviral treatment naive adults in a 48 week treatment trial. Results: During the first 4 weeks of therapy, increases in naive and memory CD4 cells and in B cells were seen; naive CD8 cells increased while CD8 ce lls remained stable as memory CD8 cells decreased. During the second phase total CD4 and naive CD4 and CD8 cells increased while total CD8 and memory CD8 cells decreased. The numbers of CD4 cells that expressed CD28 increased from a median of 308 x 10(6)/l at baseline to 477 x 10(6)/l at week 48. Hi gher baseline plasma HIV-1 RNA levels predicted the magnitude of early CD4 ( r = 0.35; P = 0.01), memory CD4 (r = 0.38; P = 0.001) and CD28 CD4 cell ( r = 0.29; P = 0.01) restoration but was not related to second phase changes . Younger age predicted a greater second phase (but not first phase) increa se in naive CD4 cells (r = -0.31; P = 0.03). Conclusions: Higher baseline levels of HIV-1 replication determine the magn itude of first phase CD4 cell increases after suppression of HIV-1 replicat ion. Second phase (primarily naive) CD4 cell increases are not related to H IV-1 replication but are inversely relate to age suggesting that thymic pot ential is a major determinant of long term cellular restoration in HIV-1 in fected persons receiving antiretroviral therapy. (C) 2000 Lippincott Willia ms & Wilkins.