title: Immunological responses and long-term treatment interruption after human immunodeficiency virus type 1 (HIV-1) lipopeptide immunization of HIV-1-infected patients: the LIPTHERA study.
abstract: We studied the time course of immunological and virological markers after highly active antiretroviral therapy (HAART) interruption in chronically human immunodeficiency virus type 1 (HIV-1)-infected patients immunized with an HIV lipopeptide preparation. In a prospective open pilot study, 24 HIV-1-infected HAART-treated patients with undetectable plasma viral loads (pVLs) and CD4(+) T-cell counts above 350/mm(3) were immunized at weeks 0, 3, and 6 with a candidate vaccine consisting of six HIV lipopeptides. At week 24, patients with pVLs of <1.7 log(10) copies/ml were invited to stop taking HAART. Antiretroviral therapy was resumed if the pVL rose above 4.47 log(10) copies/ml and/or if the CD4(+) cell count fell below 250/mm(3). Immunological and virologic parameters were studied before and after HAART interruption. The median baseline and nadir CD4(+) cell counts were 482 (interquartile range [IQR], 195 to 826) and 313 (IQR, 1 to 481)/mm(3), respectively. New specific CD8(+) cell responses to HIV-1 epitopes were detected after immunization in 13 (57%) of 23 assessable patients. Twenty-one patients were evaluated 96 weeks after HAART interruption. The median time to pVL rebound was 4 weeks (IQR, 2 to 6), and the median peak pVL was 4.26 (IQR, 3 to 5) log(10) copies/ml. Thirteen of these 21 patients resumed HAART a median of 60 weeks after immunization (IQR, 9.2 to 68.4 weeks), when the median pVL was 4.8 (IQR, 2.9 to 5.7) log(10) copies/ml and the median CD4(+) cell count was 551 (IQR, 156 to 778)/mm(3). Eight patients were still off therapy at 96 weeks, with a median pVL of 4 (IQR, 1.7 to 4.6) log(10) copies/ml and a median CD4(+) cell count of 412 (IQR, 299 to 832)/mm(3). No clinical disease progression had occurred. Despite the lack of a control arm, these findings warrant a randomized study of therapeutic vaccination with HIV lipopeptides followed by long-term HAART interruption in AIDS-free chronically infected patients.
authors.affiliation: APHP, Tenon Hospital, Paris, France. gilles.pialoux@tnn.aphp.fr
authors.forename: Gilles
authors.initials: G
authors.lastname: Pialoux
authors.forename: Romina P
authors.initials: RP
authors.lastname: Quercia
authors.forename: Hanne
authors.initials: H
authors.lastname: Gahery
authors.forename: Nathalie
authors.initials: N
authors.lastname: Daniel
authors.forename: Laurence
authors.initials: L
authors.lastname: Slama
authors.forename: Pierre-Marie
authors.initials: PM
authors.lastname: Girard
authors.forename: Philippe
authors.initials: P
authors.lastname: Bonnard
authors.forename: Willy
authors.initials: W
authors.lastname: Rozenbaum
authors.forename: Véronique
authors.initials: V
authors.lastname: Schneider
authors.forename: Dominique
authors.initials: D
authors.lastname: Salmon
authors.forename: Jean-Gérard
authors.initials: JG
authors.lastname: Guillet
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology; D000328:Adult; D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000517:prevention & control; D015497:HIV-1 / Q000276:immunology*; D054298:Human Immunodeficiency Virus Proteins / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D007114:Immunization; D008074:Lipoproteins / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010455:Peptides / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D016915:AIDS Vaccines; D019380:Anti-HIV Agents; D054298:Human Immunodeficiency Virus Proteins; D008074:Lipoproteins; D010455:Peptides; D018894:Reverse Transcriptase Inhibitors