A Double-Blind, Adjuvant-Controlled Trial of Human Immunodeficiency Virus Type 1 (HIV-1) Immunogen (Remune) Monotherapy in Asymptomatic, HIV-1-Infected Thai Subjects with CD4-Cell Counts of >300

Abstract

We examined the effect of a human immunodeficiency virus (HIV)-specific immune-based therapy in Thailand, where access to antiviral drug therapy is limited. A 40-week trial was conducted with 297 asymptomatic, HIV-infected Thai subjects with CD4-cell counts greater than 300 l/mm 3 . Subjects were randomized to receive either HIV type 1 (HIV-1) immunogen (Remune; inactivated HIV-1 from which gp120 is depleted in incomplete Freund's adjuvant or adjuvant control at 0, 12, 24, and 36 weeks at five different clinical sites in Thailand. Neither group received antiviral drug therapy. The a priori primary endpoint for the trial was changes in CD4-cell counts with secondary parameters of percent changes in CD8-cell counts (percent CD4, CD8, and CD4/CD8) and body weight. Subsets of subjects were also examined for changes in plasma HIV-1 RNA levels, Western blot immunoreactivity, and HIV-1 delayed-type hypersensitivity (DTH) skin test reactivity. There was a significant difference in changes in CD4-cell counts that favored the HIV-1 immunogen-treated group compared to those for the adjuvant-treated control group (P < 0.05). On average, for HIV-1 immunogentreated subjects CD4-cell counts increased by 84 cells by week 40, whereas the increase for the control group was 38 cells by week 40. This increase in CD4-cell count was associated with increased HIV-specific immunogenicity, as shown by Western blotting and enhanced HIV-1 DTH skin reactivity. No significant differences in adverse events were observed between the groups. The results of this trial suggest that HIV-1 immunogen is safe and significantly increases CD4-cell counts and HIV-specific immunity compared to those achieved with the adjuvant control in asymptomatic HIV-1-infected subjects not taking antiviral drugs.

Phase II placebo-controlled study of V-1 Immunitor as a therapeutic modality for treatment of HIV

“…The only notable exception among these vaccines is Remune-an injectable preparation of inactivated HIV particles stripped of gp120 envelope (Immune Response Corporation, Carlsbad, CA). In a randomized trial in Thailand, patients with comparable baseline CD4 numbers (mean 550 cells/mm 3 ) were treated for 40 weeks with Remune (Churdboonchart et al, 2000). The average elevation in CD4 counts was 84 cells while patients treated with placebo had gained 38 cells.…”

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

“…HIV-1 Immunogen is an oil and water emulsion that consists of equal volumes of inactivated virus particles in isotonic saline and IFA [19,23]. IFA is a mixture of nine parts of Drakeol 6 VR light mineral oil and one part of the surfactant Montanide 80 (mannide monoleate).…”

“…A 40-week, double-blind, placebo-controlled, randomized, phase 2 clinical trial (study P2101B) involving 297 asymptomatic, untreated HIV-infected participants was conducted in Thailand at five different clinics [19] (Table 1). The participants had CD4 T-cell counts >300 cells/μl and were immunized at 0, 12, 24, and 36 weeks.…”

“…The purification of the viral particles and subsequent inactivation by treatment with beta-propiolactone and 60 Cobalt irradiation [19,23] results in the depletion of the outer Envgp120 [23]. The viral particles contain p6 Gag , p7 Gag (nucleocapsid), p55 Gag (a precursor protein), p15 Gag and p39 Gag (intermediate proteins), p10 (protease), p17 (matrix), p24 (capsid), p32 (integrase), p51 and p66 (reverse transcriptase subunits), and the viral protein regulatory (Vpr), Vif (viral infectivity factor), and Nef (negative factor) accessory proteins [21].…”

“…HIV-1 Immunogen consists of a 1:1 mixture of whole, inactivated HIV-1 virus particles and incomplete Freund's adjuvant (IFA) [19]. Each 1-ml dose contains 10 μg of p24 in approximately 100 μg of total protein [20].…”