HIV-1 immunogen induction of HIV-1-specific delayed-type hypersensitivity: results of a double-blind, adjuvant-controlled, dose-ranging trial.
OBJECTIVE
To investigate the capacity of an HIV-1 immunogen to induce or augment HIV-1-specific delayed-type hypersensitivity (DTH) over a range of doses in asymptomatic HIV-1-seropositive adults.


METHODS
A single center, double-blind, adjuvant-controlled, dose-ranging trial involving 48 HIV-1-seropositive asymptomatic patients. Each dose group consisted of 12 subjects, eight receiving HIV-1 immunogen and four incomplete Freund's adjuvant (IFA). The doses studied were 50, 100, 200, or 400 micrograms (total protein). The HIV-1 immunogen was administered intramuscularly every 4 weeks for 36 weeks, with dosing contingent on the lack of an HIV-1 immunogen DTH response. A maximum of six doses was permitted.


METHODS
Immunogenicity was assessed every 4 weeks by DTH skin testing to the inactivated HIV-1 antigen in saline with > 9 mm induration representing a response to immunization. Changes in p24-antibody levels were determined by endpoint titration using an enzyme-linked immunosorbent assay and Western blot.


RESULTS
At doses of > or = 100 micrograms, all treated patients demonstrated significant differences in the ability to mount an HIV-1-specific cell-mediated response relative to adjuvant controls. Dose-related response patterns were observed in the period between doses and the occurrence of rises in HIV-1 DTH. Treatment appeared to increase p24-antibody titers as well as reactivities to other HIV-1 antigens as determined by Western blots. The HIV-1 immunogen was well tolerated.


CONCLUSIONS
The minimum dose of the HIV-1 immunogen in IFA required to induce HIV-1 DTH relative to the IFA control group was 100 micrograms in this patient population.
Turner
J L
JL
Graduate Hospital, Philadelphia, Pennsylvania 19146.
Trauger
R J
RJ
Daigle
A E
AE
Carlo
D J
DJ
D000328:Adult; D000917:Antibody Formation; D015153:Blotting, Western; D004311:Double-Blind Method; D005260:Female; D005620:Freund's Adjuvant; D015483:HIV Antibodies / Q000097:blood*; D016655:HIV Core Protein p24 / Q000008:administration & dosage / Q000276:immunology*; D006679:HIV Seropositivity / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D006968:Hypersensitivity, Delayed; D007111:Immunity, Cellular; D008297:Male; D008875:Middle Aged; D012882:Skin Tests
D015483:HIV Antibodies; D016655:HIV Core Protein p24; D005620:Freund's Adjuvant