Vaccine Efficacy of ALVAC-HIV and Bivalent Subtype C gp120-MF59 in Adults.
Vaccine Efficacy of ALVAC-HIV and Bivalent Subtype C gp120-MF59 in Adults.
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DOI：
10.1056/nejmoa2031499
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发表时间：
2021-03-25
期刊：
影响因子：
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通讯作者：
HVTN 702 Study Team
中科院分区：
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作者：
Gray GE;Bekker LG;Laher F;Malahleha M;Allen M;Moodie Z;Grunenberg N;Huang Y;Grove D;Prigmore B;Kee JJ;Benkeser D;Hural J;Innes C;Lazarus E;Meintjes G;Naicker N;Kalonji D;Nchabeleng M;Sebe M;Singh N;Kotze P;Kassim S;Dubula T;Naicker V;Brumskine W;Ncayiya CN;Ward AM;Garrett N;Kistnasami G;Gaffoor Z;Selepe P;Makhoba PB;Mathebula MP;Mda P;Adonis T;Mapetla KS;Modibedi B;Philip T;Kobane G;Bentley C;Ramirez S;Takuva S;Jones M;Sikhosana M;Atujuna M;Andrasik M;Hejazi NS;Puren A;Wiesner L;Phogat S;Diaz Granados C;Koutsoukos M;Van Der Meeren O;Barnett SW;Kanesa-Thasan N;Kublin JG;McElrath MJ;Gilbert PB;Janes H;Corey L;HVTN 702 Study Team
A safe, effective vaccine is essential to end HIV. A canarypox/protein HIV vaccine regimen showed modest efficacy at reducing infection in Thailand. An analogous regimen using HIV-1 subtype C virus demonstrated potent humoral and cellular responses in a Phase 1/2a trial and triggered a Phase 2b/3 double-blinded trial to assess the safety and efficacy of this regimen in South Africa. We enrolled and randomized 5,404 healthy, HIV-uninfected 18-35-year olds at 14 sites to vaccine (2,704 participants) or placebo (2,700 participants) between 26 October 2016 and 21 June 2019. The vaccine regimen consisted of two ALVAC-HIV (vCP2438) (expressing HIV-1 subtype C env, clade B gp41, gag and pro) immunizations at months 0 and 1, with booster immunizations of ALVAC-HIV plus bivalent subtype C gp120 protein/MF59 adjuvant at months 3, 6, 12 and 18. Efficacy was evaluated by HIV testing every 3 months. In January 2020, pre-specified non-efficacy criteria were met at an interim analysis; further vaccinations were subsequently halted. The vaccines were safe and well-tolerated in the study population (median age 24, 70% female-sex-at-birth). Over the primary 24-month follow-up, there were 133 infections among placebo recipients and 138 among vaccinees (hazard ratio = 1.02; 95%CI, 0.81-1.30; P=0.84). Pre-specified subgroup analyses demonstrated no difference in efficacy by sex or when restricting to follow-up post-4th vaccination, and no difference amongst female-sex-at-birth by age, BMI, prevalent STIs, behavioral risk score or region. The ALVAC/gp120 regimen did not prevent HIV infection in South Africans despite prior evidence of immunogenicity. ClinicalTrials.gov (NCT02968849)
