Response to immunization with recall and neoantigens after prolonged administration of an HIV-1 protease inhibitor-containing regimen. ACTG 375 team. AIDS Clinical Trials Group.
OBJECTIVE
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.


METHODS
Open-label study carried out at three university-affiliated AIDS Clinical Trials Units in the United States.


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. Naïve 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.
Valdez
H
H
Division of Infectious Diseases, Case Western Reserve University School of Medicine and University Hospitals of Cleveland, Ohio 44106, USA. valdez.hernan@clevelandactu.org
Smith
K Y
KY
Landay
A
A
Connick
E
E
Kuritzkes
D R
DR
Kessler
H
H
Fox
L
L
Spritzler
J
J
Roe
J
J
Lederman
M B
MB
Lederman
H M
HM
Evans
T G
TG
Heath-Chiozzi
M
M
Lederman
M M
MM
D017088:AIDS-Related Opportunistic Infections / Q000517:prevention & control; D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000276:immunology*; D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000494:pharmacology; D004359:Drug Therapy, Combination; D005260:Female; D015497:HIV-1 / Q000276:immunology*; D006433:Hemocyanins / Q000008:administration & dosage / Q000276:immunology*; D022362:Hepatitis A Vaccines; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007271:Injections, Intradermal; D019259:Lamivudine / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D019438:Ritonavir / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology; D013745:Tetanus Toxoid / Q000008:administration & dosage / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology / Q000473:pathology; D014611:Vaccination; D014761:Viral Hepatitis Vaccines / Q000008:administration & dosage / Q000276:immunology*; D015215:Zidovudine / Q000494:pharmacology
D019380:Anti-HIV Agents; D022362:Hepatitis A Vaccines; D013745:Tetanus Toxoid; D014761:Viral Hepatitis Vaccines; D019259:Lamivudine; D015215:Zidovudine; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin; D019438:Ritonavir