title: A therapeutic HIV-1 vaccine enhances anti-HIV-1 immune responses in patients under highly active antiretroviral therapy.
abstract: 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.
authors.affiliation: GeneCure Biotechnologies, Peachtree Corners, GA, USA. Electronic address: frank@genecure.com.
authors.forename: Frank Y
authors.initials: FY
authors.lastname: Tung
authors.affiliation: GeneCure Biotechnologies, Peachtree Corners, GA, USA.
authors.forename: Jack K
authors.initials: JK
authors.lastname: Tung
authors.affiliation: University of Miami, School of Medicine, Miami, FL, USA.
authors.forename: Suresh
authors.initials: S
authors.lastname: Pallikkuth
authors.affiliation: University of Miami, School of Medicine, Miami, FL, USA.
authors.forename: Savita
authors.initials: S
authors.lastname: Pahwa
authors.affiliation: University of Miami, School of Medicine, Miami, FL, USA.
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Fischl
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology / Q000627:therapeutic use*; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D004311:Double-Blind Method; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000628:therapy*; D015497:HIV-1; D006801:Humans; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000276:immunology; D008297:Male; D008875:Middle Aged; D019562:Viral Load
chemical_list: D016915:AIDS Vaccines; D016207:Cytokines; C573415:IFNG protein, human; D007371:Interferon-gamma
keywords: Analytical treatment interruption; HIV-1; Immune responses; Therapeutic vaccine; Vaccine; Viral load