Response to immunization with recall and neoantigens after prolonged administration of an HIV-1 protease inhibitor-containing regimen

Objectives: To ascertain if immunization results in the restoration of resp onses to recall antigens, in the development of responses to presumed neoan tigens, and to identify the virologic and immunologic correlates of these r esponses in persons with HIV-1 infection. Design and setting: Open-label study carried out at three university-affili ate AIDS Clinical Trials Units in the United States. Subjects and methods: Thirty-one subjects participating in AIDS Clinical Tr ials Group Protocol 375 who had received zidovudine, lamivudine, and ritona vir for at least 48 weeks. Subjects were immunized with tetanus toroid (TT) at entry and with inactivated hepatitis A vaccine (hep A) and keyhole limp et hemocyanin (KLH) at entry and 6 weeks. The development of antibody, lymp hocyte proliferative assay (LPA), and delayed-type hypersensitivity (DTH) r esponses after immunization were monitored. Results: The LPA and DTH responses to TT improved in 57 and 68% of particip ants, respectively; 73 and 65% developed enhanced LPA and DTH responses to KLH. Forty-eight percent of patients developed a four-fold increase in anti body concentration to tetanus. Seventy-three percent of patients without de tectable hepatitis A antibodies at baseline developed antibodies after, imm unization. Eighty-three percent of patients experienced at least a four-fol d rise in,KLH antibody concentration. Immune activation and viral load pred icted poor recall responses and the number of memory CD4+ T-cells predicted good responses to recall antigens. Naive CD4+ T-cell numbers, decrease in viral load, increases in CD4+ and CD28+ cells, and decreases in immune acti vation were associated with responses to presumed neoantigens.