Preliminary Evaluation of Human Immunodeficiency Virus Type 1 (HIV‐1) Immunogen in Children with HIV‐1 Infection

Abstract

The safety and preliminary activity of human immunodeficiency virus type 1 (HIV-1) immunogen were evaluated in 10 HIV-1-infected children with disease stage N1,2 or A1,2. Multiple inoculations of 2. 5 or 10 units (U) of HIV-1 immunogen were safe and well tolerated without an acceleration of disease progression. When antiretroviral agents were coadministered, the 10 U dose appeared to be associated with more sustained reduction in plasma HIV-1 RNA than the 2.5 U dose (median log10 HIV-1 RNA at month 18, 3.07 vs. 4.01 copies/mL in 10 U [n=4] vs. 2.5 U [n=3], respectively; P=.034). Levels of regulated-on-activation, normal T cell-expressed and -secreted chemokine produced from HIV-1 immunogen-stimulated lymphocytes in vitro were increased in the children who had HIV-1 immunogen-specific antibody responses (P<.02) and appeared to be inversely correlated with levels of plasma HIV-1 RNA (P<.01). These preliminary data warrant larger studies to determine the effectiveness of adjunctive therapy with HIV-1 immunogen in children with HIV-1 infection.

Highly active antiretroviral therapy restores in vitro mitogen and antigen-specific T-lymphocyte responses in HIV-1 perinatally infected children despite virological failure

“…HIV-1 infection leads to a severe depletion of CD4 + Tlymphocytes in adults and children [1]. This decrease is associated with a progressive impairment of immune function.…”

HIV-1 Immunogen: an overview of almost 30 years of clinical testing of a candidate therapeutic vaccine

“…HIV-1 Immunogen was tested in 10 children who varied in disease stage in a double-blind, dose-ranging, phase 1 study that compared the adult dose (10 units; n = 5) to a lower dose (2.5 units; n = 5) [32] (Table 1). Nine of the 10 children were treated with either AZT, ddI, or both during the study.…”

“…HIV-1 Immunogen has been tested extensively in more than a dozen clinical trials over the course of almost three decades; these trials have involved more than 2000 HIV-infected individuals [14,15,19,[23][24][25][26][27][28][29][30][31][32][33][35][36][37][38][40][41][42]44] including children [32].…”

“…This candidate therapeutic vaccine has an excellent safety profile as it does not adversely affect CD4 T-cell counts and/or percentages, HIV-1 VL, body weight or HIV disease progression [14,15,19,[23][24][25][26][27][28][29][30][31][32][33][35][36][37][38][40][41][42]44]. In some clinical trials, improvements in some of these clinical safety parameters have been reported [19,23,[25][26][27]35,36,38,40,42,44].…”

“…The most common AE reported following immunization with HIV-1 Immunogen is a mild, transient injection site reaction [14,15,19,25,26,32,33,37,44]. The IFA component of the vaccine rather than HIV viral Ag is the most likely cause of these AEs [41], since AEs occur at comparable frequencies in participants receiving HIV-1 Immunogen and participants receiving the IFA placebo [19,41,42].…”