Can immune markers predict subsequent discordance between immunologic and virologic responses to antiretroviral therapy? Adult AIDS Clinical Trials Group

It is unclear why discordant immunologic and virologic responses occur during therapy for human immunodeficiency virus (HIV) infection. This study examined whether markers of immune activation and naive/memory lymphocyte subsets at study baseline could predict discordance between HIV type 1 (HIV-1) RNA and CD4⁺ lymphocyte responses at week 24 of antiretroviral therapy. Ten diverse, prospective antiretroviral studies with 1007 evaluable subjects were included. Subsets of subjects at increased risk for discordance were identified by recursive partitioning. The strongest predictor of more-favorable immunologic than virologic responses was a lower baseline CD4⁺ lymphocyte count. Weaker predictors in small subsets of subjects were fewer activated CD4⁺ lymphocytes and fewer CD8 ⁺ lymphocytes. Conversely, the strongest predictors of more-favorable virologic than immunologic responses were higher baseline CD4⁺ lymphocyte count and percentage. Additional predictors in some analyses were higher CD8⁺ lymphocyte count or percentage and lower HIV-1 RNA concentrations. Baseline markers of immune activation and naive/ memory lymphocyte subsets had limited ability to predict subsequent discordance.