A therapeutic HIV-1 vaccine enhances anti-HIV-1 immune responses in patients under highly active antiretroviral therapy.
BACKGROUND
HIV-1 specific cellular immunity plays an important role in controlling viral replication. In this first-in-human therapeutic vaccination study, a replication-defective HIV-1 vaccine (HIVAX) was tested in HIV-1 infected participants undergoing highly active antiretroviral therapy (HAART) to enhance anti-HIV immunity (Clinicaltrials.gov, identifier NCT01428596).


METHODS
A010 was a randomized, placebo-controlled trial to evaluate the safety and the immunogenicity of a replication defective HIV-1 vaccine (HIVAX) given as a subcutaneous injection to HIV-1 infected participants who were receiving HAART with HIV-1 viral load <50 copies/ml and CD4 cell count >500 cells/mm(3). HIV-1 specific immune responses were monitored by INF-γ enzyme linked immunospot (Elispot) and intracellular cytokine staining (ICS) assay after vaccination. Following the randomized placebo-controlled vaccination phase, subjects who received HIVAX vaccine and who met eligibility underwent a 12-week analytical antiretroviral treatment interruption (ATI). Viral load was monitored throughout the study.


RESULTS
HIVAX was well tolerated in trial participants. Transient grade 1 to 2 (mild to moderate) injection site reactions occurred in 8 of 10 vaccinated participants. HIVAX was immunogenic in all vaccinated participants. The functionality of T cells was significantly enhanced after vaccination. Median viral load (3.45 log10 copies/ml, range of 96-12,830 copies/ml) at the end of the 12-week treatment interruption in HIVAX vaccinated group was significantly lower than the pre-treatment levels. Three vaccinated participants extended ATI for up to 2 years with stable CD4 cells and low viral loads.


CONCLUSIONS
HIVAX vaccine is generally safe, elicits strong anti-HIV-1 immune responses, and may play an important role in controlling viral load during treatment interruption in HIV-1 infected participants.
['Tung|Frank Y|FY|', 'Tung|Jack K|JK|', 'Pallikkuth|Suresh|S|', 'Pahwa|Savita|S|', 'Fischl|Margaret A|MA|']
D016915:AIDS Vaccines D000328:Adult D023241:Antiretroviral Therapy, Highly Active D018791:CD4 Lymphocyte Count D015496:CD4-Positive T-Lymphocytes D018414:CD8-Positive T-Lymphocytes D016207:Cytokines D004311:Double-Blind Method D005260:Female D015658:HIV Infections D015497:HIV-1 D006801:Humans D007111:Immunity, Cellular D007371:Interferon-gamma D008297:Male D008875:Middle Aged D019562:Viral Load
HIV-1 Vaccine Immune responses Therapeutic vaccine Viral load Analytical treatment interruption