Induction of HIV-1-specific CD4+ T-cell responses by therapeutic vaccination represents an attractive intervention to potentially increase immune control of HIV-1.We performed a double-blinded, randomized, placebo-controlled clinical trial to determine the safety and immunogenicity of GlaxoSmithKline Biologicals' HIV-1 gp120/NefTat subunit protein vaccine formulated with the AS02A Adjuvant System in subjects with well-controlled chronic HIV-1 infection on highly active antiretroviral therapy. Ten individuals received the vaccine; whereas adjuvant alone or placebo was given to 5 subjects each. Immunogenicity was monitored by intracellular cytokine flow cytometry and carboxyfluorescein succinimidyl ester-based proliferation assays.The vaccine was well tolerated with no related serious adverse events. Vaccine recipients had significantly stronger gp120-specific CD4+ T-cell responses which persisted until week 48 and greater gp120-specific CD4+ T-cell proliferation activity as compared with controls. In the vaccine group, the number of participants who demonstrated positive responses for both gp120-specific CD4+ T-cell interleukin-2 production and gp120-specific CD8+ T-cell proliferation were significantly higher at week 6.The gp120/NefTat/AS02A vaccine induced strong gp120-specific CD4+ T-cell responses and a higher number of vaccinees developed both HIV-1-specific CD4+ T-cell responses and CD8+ T-cell proliferation. The induction of these responses may be important in enhancing immune-mediated viral control. [ABSTRACT FROM AUTHOR]