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HIV-1 immunotherapy offers an alternative to cART or as a “functional cure” by eliminating reactivated viral reservoirs. Both cellular and antibody mediated immune responses have been identified which are capable of reducing either HIV-1 infection risk or severity of infection. We present data on both T-cell based (Vacc4x) and antibody based (vacc-C5) vaccine antigen under development for HIV-1 immunotherapy. Vacc4x has undergone phase II trials demonstrating reductions in viral load and sustained anti-HIV-1 T-cell responses. Additional immune modulation, such as that used in cancer immunotherapy, may have utility in HIV-1 Immunotherapy. For this reason we combined Vacc4x with the immune modulator Lenalidomide both in vitro and in a phase I trial of 24 subjects in order to assess the ability of this combination to enhance CD4+ T cell responses. The combination was safe, well tolerated and demonstrated increases in CD4+ T-cell counts after a 2 week vaccine protocol. We have identified that antibodies specific for a heterodimeric peptide construct comprising the C5501-512 and gp41732-744 regions of the HIV envelope protein (Vacc-C5) are correlated with slow disease progression, lower viral load and markers of immune function in HIV-1 patients and are capable of mediating antibody dependent cytotoxicity. We conducted a phase I/II trial of 36 ART treated patients vaccinated with Vacc-C5 antigen. Vacc-C5 was safe, well tolerated and increased anti-Vacc-C5 titre in a subset of patients. These data support the continued development of Vacc4x, Lenalidomide and Vacc-C5 in an HIV-1 immunotherapeutic setting.