From the Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center (G.E.G., Z.M., N. Grunenberg, Y.H., D.G., B.P., J.J.K., J.H., C.B., S.R., S.T., M.J., M. Sikhosana, M. Andrasik, J.G.K., M.J.M., P.B.G., H.J., L.C.), Seattle; the Perinatal HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand (G.E.G., F.L., E.L., B.M., T.P., S.T.), the National Institute for Communicable Diseases, National Health Laboratory Service (A.P.), and Aurum Institute (C.I., M. Sebe, W.B., P.S., T.A., G. Kobane), Johannesburg, Desmond Tutu HIV Centre (L.-G.B., S.K., C.N.N., M. Atujuna), the Department of Medicine, Wellcome Centre for Infectious Diseases Research in Africa, and Institute of Infectious Disease and Molecular Medicine (G.M., A.M.W.), and the Division of Clinical Pharmacology, Department of Medicine (L.W.), University of Cape Town, Cape Town, Setshaba Research Centre, Soshanguve (M.M., K.S.M.), Mecru Clinical Research Unit, Sefako Mkgatho Health Sciences University, Ga-Rankuwa (M.N., M.P.M.), Nelson Mandela Academic Clinical Research Unit and Department of Internal Medicine and Pharmacology, Walter Sisulu University, Mthatha (T.D., P.M.), the School of Health Systems and Public Health, Faculty of Health Sciences, University of Pretoria, Pretoria (S.T.), the South African Medical Research Council (G.E.G., D.K., N.S., V.N., G. Kistnasami, Z.G.) and the Centre for the AIDS Programme of Research in South Africa, University of KwaZulu-Natal (N.N., N. Garrett), Durban, and Qhakaza Mbokodo Research Clinic, Ladysmith (P.K., P.B.M.) - all in South Africa; the Vaccine Research Program, Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda (M. Allen), and GlaxoSmithKline Vaccines, Rockville (N.K.-T.) - both in Maryland; the Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta (D.B.); GSK Vaccines, Cambridge, MA (S.W.B.); Sanofi Pasteur, Swiftwater, PA (S.P., C.D.G.); GlaxoSmithKline, Siena, Italy (S.P.); GlaxoSmithKline, Wavre (M.K.), and GlaxoSmithKline, Rixensart (O.V.D.M.) - both in Belgium; and the Graduate Group in Biostatistics and the Center for Computational Biology, University of California, Berkeley (N.S.H.).
N Engl J Med. 2021 Mar 25;384(12):1089-1100. doi: 10.1056/NEJMoa2031499.
A safe, effective vaccine is essential to eradicating human immunodeficiency virus (HIV) infection. A canarypox-protein HIV vaccine regimen (ALVAC-HIV plus AIDSVAX B/E) showed modest efficacy in reducing infection in Thailand. An analogous regimen using HIV-1 subtype C virus showed potent humoral and cellular responses in a phase 1-2a trial in South Africa. Efficacy data and additional safety data were needed for this regimen in a larger population in South Africa.
In this phase 2b-3 trial, we randomly assigned 5404 adults without HIV-1 infection to receive the vaccine (2704 participants) or placebo (2700 participants). The vaccine regimen consisted of injections of ALVAC-HIV at months 0 and 1, followed by four booster injections of ALVAC-HIV plus bivalent subtype C gp120-MF59 adjuvant at months 3, 6, 12, and 18. The primary efficacy outcome was the occurrence of HIV-1 infection from randomization to 24 months.
In January 2020, prespecified criteria for nonefficacy were met at an interim analysis; further vaccinations were subsequently halted. The median age of the trial participants was 24 years; 70% of the participants were women. The incidence of adverse events was similar in the vaccine and placebo groups. During the 24-month follow-up, HIV-1 infection was diagnosed in 138 participants in the vaccine group and in 133 in the placebo group (hazard ratio, 1.02; 95% confidence interval, 0.81 to 1.30; P = 0.84).
The ALVAC-gp120 regimen did not prevent HIV-1 infection among participants in South Africa despite previous evidence of immunogenicity. (HVTN 702 ClinicalTrials.gov number, NCT02968849.).
安全有效的疫苗对于消灭人类免疫缺陷病毒（HIV）感染至关重要。一种使用禽痘病毒载体和 HIV 蛋白的疫苗方案（ALVAC-HIV 加 AIDSVAX B/E）在泰国的临床试验中显示出了适度的降低感染的效果。在南非进行的一项 1-2a 期临床试验中，一种使用 HIV-1 亚型 C 病毒的类似方案显示出了强大的体液和细胞免疫反应。需要在南非更大的人群中获得该方案的疗效数据和更多的安全性数据。
在这项 2b-3 期临床试验中，我们将 5404 名未感染 HIV-1 的成年人随机分配接受疫苗（2704 名参与者）或安慰剂（2700 名参与者）。疫苗方案包括在 0 个月和 1 个月时注射 ALVAC-HIV，然后在 3 个月、6 个月、12 个月和 18 个月时注射四次 ALVAC-HIV 加双价 C 型 gp120-MF59 佐剂的加强针。主要疗效终点是从随机分组到 24 个月时发生 HIV-1 感染的情况。
在 2020 年 1 月，中期分析达到了无效的预先指定标准；随后停止了进一步的疫苗接种。试验参与者的中位年龄为 24 岁；70%的参与者为女性。疫苗组和安慰剂组的不良事件发生率相似。在 24 个月的随访期间，疫苗组中有 138 名参与者被诊断出 HIV-1 感染，安慰剂组中有 133 名参与者被诊断出 HIV-1 感染（风险比，1.02；95%置信区间，0.81 至 1.30；P=0.84）。
尽管先前有免疫原性的证据，但在南非的参与者中，ALVAC-gp120 方案并不能预防 HIV-1 感染。（HVTN 702 临床试验.gov 编号，NCT02968849。）
