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

Hernan Valdez, Kimberly Y. Smith, Alan Landay, Elizabeth Connick, Daniel R. Kuritzkes, Harold Kessler, Lawrence Fox, John Spritzler, Joana Roe, Miriam B. Lederman, Howard M. Lederman, Thomas G. Evans, Margo Heath-Chiozzi, Michael M. Lederman

Research output: Contribution to journalArticlepeer-review


Objectives: To ascertain if immunization results in the restoration of responses to recall antigens, in the development of responses to presumed neoantigens, and to identify the virologic and immunologic correlates of these responses in persons with HIV-1 infection. Design and setting: Open-label study carried out at three university-affiliate AIDS Clinical Trials Units in the United States. Subjects and methods: Thirty-one subjects participating in AIDS Clinical Trials Group Protocol 375 who had received zidovudine, lamivudine, and ritonavir for at least 48 weeks. Subjects were immunized with tetanus toxoid (TT) at entry and with inactivated hepatitis A vaccine (hep A) and keyhole limpet hemocyanin (KLH) at entry and 6 weeks. The development of antibody, lymphocyte proliferative assay (LPA), and delayed-type hypersensitivity (DTH) responses after immunization were monitored. Results: The LPA and DTH responses to TT improved in 57 and 68 of participants, respectively; 73 and 65 developed enhanced LPA and DTH responses to KLH. Forty-eight percent of patients developed a four-fold increase in antibody concentration to tetanus. Seventy-three percent of patients without detectable hepatitis A antibodies at baseline developed antibodies after immunization. Eighty-three percent of patients experienced at least a four-fold rise in KLH antibody concentration. Immune activation and viral load predicted 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 activation were associated with responses to presumed neoantigens. Conclusions: Most HIV-infected patients treated with potent combination antiretrovirals develop responses to recall and presumed neoantigens after immunization. Functional immune restoration in response to immunization is related to control of viral replication, decreased immune activation as well as to both quantitative and qualitative restoration of circulating T- lymphocyte subpopulations. (C) 2000 Lippincott Williams and Wilkins.

Original languageEnglish (US)
Pages (from-to)11-21
Number of pages11
Issue number1
StatePublished - 2000
Externally publishedYes


  • Antibodies
  • Antiretroviral therapy
  • Delayed-type hypersensitivity responses
  • Hepatitis A
  • Immune activation
  • Immunization
  • Keyhole limpet hemocyanin
  • Lymphocyte proliferative responses
  • Pathogenesis
  • Protease inhibitors
  • Tetanus toxoid

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases


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