DNA immunization with HIV early genes in HIV type 1-infected patients on highly active antiretroviral therapy.
The aim of this study was to evaluate the immunological responses induced by DNA plasmids containing HIV regulatory genes administered in combination in HIV-1-infected patients with pretreatment with highly active antiretroviral treatment (HAART). The study is a double-blind, randomized, and placebo-controlled study, including 15 asymptomatic HIV-1-infected patients on stable HAART for at least 6 months and with plasma HIV RNA levels below 50 copies/ml. Ten patients received a combination of rev, tat, and nef intramuscularly (im) at weeks 0, 4, and 16 at increasing doses giving totals of 300 (100 x 3), 900 (300 x 3), and 1800 (600 x 3) micrograms DNA. Five patients received saline in the same amounts im. Antigen-specific cytotoxic T lymphocyte (CTL) levels were preserved or increased and new T lymphocyte proliferative responses were induced in the group immunized with the HIV DNA genes. No increase in antibody levels was noted. Despite a 10-fold higher vaccine dose, patients on HAART did not respond better to vaccination compared to non-HAART patients included in a previous study where the genes were administered separately. Combining the regulatory genes rev, tat, and nef in increasing doses may reduce the anticipated augmentation of HIV-specific T cell proliferative and CTL responses. Viral suppression did not seem to further improve the initial vaccine responses of patients with comparable CD4 levels.
Venhälsan, Karolinska Institute, South Stockholm General Hospital, S-118 83 Stockholm, Sweden. Bo.Hejdeman@sos.sll.se
B
B
Hejdeman
A C
AC
Boström
R
R
Matsuda
S
S
Calarota
R
R
Lenkei
E L
EL
Fredriksson
E
E
Sandström
G
G
Bratt
B
B
Wahren
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D019380:Anti-HIV Agents / Q000627:therapeutic use; D000956:Antigens, Viral / Q000096:biosynthesis; D023241:Antiretroviral Therapy, Highly Active; D004311:Double-Blind Method; D005814:Genes, Viral; D015658:HIV Infections / Q000276:immunology* / Q000628:therapy*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology; D006801:Humans; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*; D019562:Viral Load
D016915:AIDS Vaccines; D019380:Anti-HIV Agents; D000956:Antigens, Viral; D019444:Vaccines, DNA