The F4/AS01B HIV-1 Vaccine Candidate Is Safe and Immunogenic, but Does Not Show Viral Efficacy in Antiretroviral Therapy-Naive, HIV-1-Infected Adults: A Randomized Controlled Trial

Warren Dinges, Pierre Marie Girard, Daniel Podzamczer, Norbert H. Brockmeyer, Felipe García, Thomas Harrer, Jean Daniel Lelievre, Ian Frank, Nathalie Colin De Verdière, Guy Patrick Yeni, Enrique Ortega Gonzalez, Rafael Rubio, Bonaventura Clotet Sala, Edwin DeJesus, Maria Jesus Pérez-Elias, Odile Launay, Gilles Pialoux, Jihad Slim, Laurence Weiss, Olivier BouchaudFranco Felizarta, Anja Meurer, François Raffi, Stefan Esser, Christine Katlama, Susan L. Koletar, Karam Mounzer, Susan Swindells, John D. Baxter, Stefan Schneider, Julie Chas, Jean Michel Molina, Marguerite Koutsoukos, Alix Collard, Patricia Bourguignon, François Roman

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The impact of the investigational human immunodeficiency virus type 1 (HIV-1) F4/AS01B vaccine on HIV-1 viral load (VL) was evaluated in antiretroviral therapy (ART)-naive HIV-1 infected adults. This phase IIb, observer-blind study (NCT01218113), included ART-naive HIV-1 infected adults aged 18 to 55 years. Participants were randomized to receive 2 (F4/AS01B-2 group, N=64) or 3 (F4/ AS01B-3 group, N=62) doses of F4/AS01B or placebo (control group, N=64) at weeks 0, 4, and 28. Efficacy (HIV-1 VL, CD8+ T-cell count, ART initiation, and HIV-related clinical events), safety, and immunogenicity (antibody and T-cell responses) were evaluated during 48 weeks. At week 48, based on a mixed model, no statistically significant difference in HIV-1 VL change from baseline was demonstrated between F4/AS01B-2 and control group (0.073 log10 copies/mL [97.5% confidence interval (CI):-0.088; 0.235]), or F4/AS01B-3 and control group (-0.096 log10 copies/mL [97.5% CI:-0.257; 0.065]). No differences between groups were observed in HIV-1 VL change, CD8+ T-cell count, ART initiation, or HIV-related clinical events at intermediate timepoints. Among F4/AS01B recipients, the most frequent solicited symptoms were pain at injection site (252/300 doses), fatigue (137/300 doses), myalgia (105/300 doses), and headache (90/300 doses). Twelve serious adverse events were reported in 6 participants; 1 was considered vaccine-related (F4/ AS01B-2 group: Angioedema). F4/AS01B induced polyfunctional F4-specific CD8+ T-cells, but had no significant impact on F4-specific CD8+ T-cell and anti-F4 antibody levels. F4/AS01B had a clinically acceptable safety profile, induced F4-specific CD8+ T-cell responses, but did not reduce HIV-1 VL, impact CD8+ T-cells count, delay ART initiation, or prevent HIV-1 related clinical events.

Original languageEnglish (US)
Article numbere2673
JournalMedicine (United States)
Volume95
Issue number6
DOIs
StatePublished - Feb 1 2016

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HIV-1
Vaccines
Randomized Controlled Trials
Viral Load
T-Lymphocytes
Therapeutics
Cell Count
Control Groups
HIV
Confidence Intervals
Safety
Angioedema
Myalgia
Fatigue
Headache
Anti-Idiotypic Antibodies
Placebos
Pain
Injections
Antibodies

ASJC Scopus subject areas

  • Medicine(all)

Cite this

The F4/AS01B HIV-1 Vaccine Candidate Is Safe and Immunogenic, but Does Not Show Viral Efficacy in Antiretroviral Therapy-Naive, HIV-1-Infected Adults : A Randomized Controlled Trial. / Dinges, Warren; Girard, Pierre Marie; Podzamczer, Daniel; Brockmeyer, Norbert H.; García, Felipe; Harrer, Thomas; Lelievre, Jean Daniel; Frank, Ian; De Verdière, Nathalie Colin; Yeni, Guy Patrick; Gonzalez, Enrique Ortega; Rubio, Rafael; Sala, Bonaventura Clotet; DeJesus, Edwin; Pérez-Elias, Maria Jesus; Launay, Odile; Pialoux, Gilles; Slim, Jihad; Weiss, Laurence; Bouchaud, Olivier; Felizarta, Franco; Meurer, Anja; Raffi, François; Esser, Stefan; Katlama, Christine; Koletar, Susan L.; Mounzer, Karam; Swindells, Susan; Baxter, John D.; Schneider, Stefan; Chas, Julie; Molina, Jean Michel; Koutsoukos, Marguerite; Collard, Alix; Bourguignon, Patricia; Roman, François.

In: Medicine (United States), Vol. 95, No. 6, e2673, 01.02.2016.

Research output: Contribution to journalArticle

Dinges, W, Girard, PM, Podzamczer, D, Brockmeyer, NH, García, F, Harrer, T, Lelievre, JD, Frank, I, De Verdière, NC, Yeni, GP, Gonzalez, EO, Rubio, R, Sala, BC, DeJesus, E, Pérez-Elias, MJ, Launay, O, Pialoux, G, Slim, J, Weiss, L, Bouchaud, O, Felizarta, F, Meurer, A, Raffi, F, Esser, S, Katlama, C, Koletar, SL, Mounzer, K, Swindells, S, Baxter, JD, Schneider, S, Chas, J, Molina, JM, Koutsoukos, M, Collard, A, Bourguignon, P & Roman, F 2016, 'The F4/AS01B HIV-1 Vaccine Candidate Is Safe and Immunogenic, but Does Not Show Viral Efficacy in Antiretroviral Therapy-Naive, HIV-1-Infected Adults: A Randomized Controlled Trial', Medicine (United States), vol. 95, no. 6, e2673. https://doi.org/10.1097/MD.0000000000002673
Dinges, Warren ; Girard, Pierre Marie ; Podzamczer, Daniel ; Brockmeyer, Norbert H. ; García, Felipe ; Harrer, Thomas ; Lelievre, Jean Daniel ; Frank, Ian ; De Verdière, Nathalie Colin ; Yeni, Guy Patrick ; Gonzalez, Enrique Ortega ; Rubio, Rafael ; Sala, Bonaventura Clotet ; DeJesus, Edwin ; Pérez-Elias, Maria Jesus ; Launay, Odile ; Pialoux, Gilles ; Slim, Jihad ; Weiss, Laurence ; Bouchaud, Olivier ; Felizarta, Franco ; Meurer, Anja ; Raffi, François ; Esser, Stefan ; Katlama, Christine ; Koletar, Susan L. ; Mounzer, Karam ; Swindells, Susan ; Baxter, John D. ; Schneider, Stefan ; Chas, Julie ; Molina, Jean Michel ; Koutsoukos, Marguerite ; Collard, Alix ; Bourguignon, Patricia ; Roman, François. / The F4/AS01B HIV-1 Vaccine Candidate Is Safe and Immunogenic, but Does Not Show Viral Efficacy in Antiretroviral Therapy-Naive, HIV-1-Infected Adults : A Randomized Controlled Trial. In: Medicine (United States). 2016 ; Vol. 95, No. 6.
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abstract = "The impact of the investigational human immunodeficiency virus type 1 (HIV-1) F4/AS01B vaccine on HIV-1 viral load (VL) was evaluated in antiretroviral therapy (ART)-naive HIV-1 infected adults. This phase IIb, observer-blind study (NCT01218113), included ART-naive HIV-1 infected adults aged 18 to 55 years. Participants were randomized to receive 2 (F4/AS01B-2 group, N=64) or 3 (F4/ AS01B-3 group, N=62) doses of F4/AS01B or placebo (control group, N=64) at weeks 0, 4, and 28. Efficacy (HIV-1 VL, CD8+ T-cell count, ART initiation, and HIV-related clinical events), safety, and immunogenicity (antibody and T-cell responses) were evaluated during 48 weeks. At week 48, based on a mixed model, no statistically significant difference in HIV-1 VL change from baseline was demonstrated between F4/AS01B-2 and control group (0.073 log10 copies/mL [97.5{\%} confidence interval (CI):-0.088; 0.235]), or F4/AS01B-3 and control group (-0.096 log10 copies/mL [97.5{\%} CI:-0.257; 0.065]). No differences between groups were observed in HIV-1 VL change, CD8+ T-cell count, ART initiation, or HIV-related clinical events at intermediate timepoints. Among F4/AS01B recipients, the most frequent solicited symptoms were pain at injection site (252/300 doses), fatigue (137/300 doses), myalgia (105/300 doses), and headache (90/300 doses). Twelve serious adverse events were reported in 6 participants; 1 was considered vaccine-related (F4/ AS01B-2 group: Angioedema). F4/AS01B induced polyfunctional F4-specific CD8+ T-cells, but had no significant impact on F4-specific CD8+ T-cell and anti-F4 antibody levels. F4/AS01B had a clinically acceptable safety profile, induced F4-specific CD8+ T-cell responses, but did not reduce HIV-1 VL, impact CD8+ T-cells count, delay ART initiation, or prevent HIV-1 related clinical events.",
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T1 - The F4/AS01B HIV-1 Vaccine Candidate Is Safe and Immunogenic, but Does Not Show Viral Efficacy in Antiretroviral Therapy-Naive, HIV-1-Infected Adults

T2 - A Randomized Controlled Trial

AU - Dinges, Warren

AU - Girard, Pierre Marie

AU - Podzamczer, Daniel

AU - Brockmeyer, Norbert H.

AU - García, Felipe

AU - Harrer, Thomas

AU - Lelievre, Jean Daniel

AU - Frank, Ian

AU - De Verdière, Nathalie Colin

AU - Yeni, Guy Patrick

AU - Gonzalez, Enrique Ortega

AU - Rubio, Rafael

AU - Sala, Bonaventura Clotet

AU - DeJesus, Edwin

AU - Pérez-Elias, Maria Jesus

AU - Launay, Odile

AU - Pialoux, Gilles

AU - Slim, Jihad

AU - Weiss, Laurence

AU - Bouchaud, Olivier

AU - Felizarta, Franco

AU - Meurer, Anja

AU - Raffi, François

AU - Esser, Stefan

AU - Katlama, Christine

AU - Koletar, Susan L.

AU - Mounzer, Karam

AU - Swindells, Susan

AU - Baxter, John D.

AU - Schneider, Stefan

AU - Chas, Julie

AU - Molina, Jean Michel

AU - Koutsoukos, Marguerite

AU - Collard, Alix

AU - Bourguignon, Patricia

AU - Roman, François

PY - 2016/2/1

Y1 - 2016/2/1

N2 - The impact of the investigational human immunodeficiency virus type 1 (HIV-1) F4/AS01B vaccine on HIV-1 viral load (VL) was evaluated in antiretroviral therapy (ART)-naive HIV-1 infected adults. This phase IIb, observer-blind study (NCT01218113), included ART-naive HIV-1 infected adults aged 18 to 55 years. Participants were randomized to receive 2 (F4/AS01B-2 group, N=64) or 3 (F4/ AS01B-3 group, N=62) doses of F4/AS01B or placebo (control group, N=64) at weeks 0, 4, and 28. Efficacy (HIV-1 VL, CD8+ T-cell count, ART initiation, and HIV-related clinical events), safety, and immunogenicity (antibody and T-cell responses) were evaluated during 48 weeks. At week 48, based on a mixed model, no statistically significant difference in HIV-1 VL change from baseline was demonstrated between F4/AS01B-2 and control group (0.073 log10 copies/mL [97.5% confidence interval (CI):-0.088; 0.235]), or F4/AS01B-3 and control group (-0.096 log10 copies/mL [97.5% CI:-0.257; 0.065]). No differences between groups were observed in HIV-1 VL change, CD8+ T-cell count, ART initiation, or HIV-related clinical events at intermediate timepoints. Among F4/AS01B recipients, the most frequent solicited symptoms were pain at injection site (252/300 doses), fatigue (137/300 doses), myalgia (105/300 doses), and headache (90/300 doses). Twelve serious adverse events were reported in 6 participants; 1 was considered vaccine-related (F4/ AS01B-2 group: Angioedema). F4/AS01B induced polyfunctional F4-specific CD8+ T-cells, but had no significant impact on F4-specific CD8+ T-cell and anti-F4 antibody levels. F4/AS01B had a clinically acceptable safety profile, induced F4-specific CD8+ T-cell responses, but did not reduce HIV-1 VL, impact CD8+ T-cells count, delay ART initiation, or prevent HIV-1 related clinical events.

AB - The impact of the investigational human immunodeficiency virus type 1 (HIV-1) F4/AS01B vaccine on HIV-1 viral load (VL) was evaluated in antiretroviral therapy (ART)-naive HIV-1 infected adults. This phase IIb, observer-blind study (NCT01218113), included ART-naive HIV-1 infected adults aged 18 to 55 years. Participants were randomized to receive 2 (F4/AS01B-2 group, N=64) or 3 (F4/ AS01B-3 group, N=62) doses of F4/AS01B or placebo (control group, N=64) at weeks 0, 4, and 28. Efficacy (HIV-1 VL, CD8+ T-cell count, ART initiation, and HIV-related clinical events), safety, and immunogenicity (antibody and T-cell responses) were evaluated during 48 weeks. At week 48, based on a mixed model, no statistically significant difference in HIV-1 VL change from baseline was demonstrated between F4/AS01B-2 and control group (0.073 log10 copies/mL [97.5% confidence interval (CI):-0.088; 0.235]), or F4/AS01B-3 and control group (-0.096 log10 copies/mL [97.5% CI:-0.257; 0.065]). No differences between groups were observed in HIV-1 VL change, CD8+ T-cell count, ART initiation, or HIV-related clinical events at intermediate timepoints. Among F4/AS01B recipients, the most frequent solicited symptoms were pain at injection site (252/300 doses), fatigue (137/300 doses), myalgia (105/300 doses), and headache (90/300 doses). Twelve serious adverse events were reported in 6 participants; 1 was considered vaccine-related (F4/ AS01B-2 group: Angioedema). F4/AS01B induced polyfunctional F4-specific CD8+ T-cells, but had no significant impact on F4-specific CD8+ T-cell and anti-F4 antibody levels. F4/AS01B had a clinically acceptable safety profile, induced F4-specific CD8+ T-cell responses, but did not reduce HIV-1 VL, impact CD8+ T-cells count, delay ART initiation, or prevent HIV-1 related clinical events.

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