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Clinical Trial
. 2021 Mar 25;384(12):1089-1100.
doi: 10.1056/NEJMoa2031499.

Vaccine Efficacy of ALVAC-HIV and Bivalent Subtype C gp120-MF59 in Adults

Glenda E Gray  1 , Linda-Gail Bekker  1 , Fatima Laher  1 , Mookho Malahleha  1 , Mary Allen  1 , Zoe Moodie  1 , Nicole Grunenberg  1 , Yunda Huang  1 , Doug Grove  1 , Brittany Prigmore  1 , Jia J Kee  1 , David Benkeser  1 , John Hural  1 , Craig Innes  1 , Erica Lazarus  1 , Graeme Meintjes  1 , Nivashnee Naicker  1 , Dishiki Kalonji  1 , Maphoshane Nchabeleng  1 , Modulakgotla Sebe  1 , Nishanta Singh  1 , Philip Kotze  1 , Sheetal Kassim  1 , Thozama Dubula  1 , Vimla Naicker  1 , William Brumskine  1 , Cleon N Ncayiya  1 , Amy M Ward  1 , Nigel Garrett  1 , Girisha Kistnasami  1 , Zakir Gaffoor  1 , Pearl Selepe  1 , Philisiwe B Makhoba  1 , Matsontso P Mathebula  1 , Pamela Mda  1 , Tania Adonis  1 , Katlego S Mapetla  1 , Bontle Modibedi  1 , Tricia Philip  1 , Gladys Kobane  1 , Carter Bentley  1 , Shelly Ramirez  1 , Simbarashe Takuva  1 , Megan Jones  1 , Mpho Sikhosana  1 , Millicent Atujuna  1 , Michele Andrasik  1 , Nima S Hejazi  1 , Adrian Puren  1 , Lubbe Wiesner  1 , Sanjay Phogat  1 , Carlos Diaz Granados  1 , Marguerite Koutsoukos  1 , Olivier Van Der Meeren  1 , Susan W Barnett  1 , Niranjan Kanesa-Thasan  1 , James G Kublin  1 , M Juliana McElrath  1 , Peter B Gilbert  1 , Holly Janes  1 , Lawrence Corey  1 ; HVTN 702 Study Team
Collaborators, Affiliations
Clinical Trial

Vaccine Efficacy of ALVAC-HIV and Bivalent Subtype C gp120-MF59 in Adults

Glenda E Gray et al. N Engl J Med. .

Abstract

Background: 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.

Methods: 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.

Results: 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).

Conclusions: 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.).

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Figures

Figure 1
Figure 1
Screening, randomization, enrollment, and study outcomes. ¥Top 3 reasons for ineligibility shown. *4 participants were screened and found ineligible but sex-at-birth not recorded. +3 participants were randomized and enrolled twice and only data from the first randomization and enrollment is considered. §Participant is not in Month 6.5 at-risk cohort because no HIV diagnostic test was performed after Month 6.5 and prior to study unblinding. ‡Other product administration errors include incorrect site of administration, product expired, and other.
Figure 2
Figure 2
Cumulative incidence of HIV-1 infection. A. MITT cohort, 0-24 months. B. Month 6.5 at-risk cohort, 6.5-24 months. C. MITT cohort, 0-36 months. Inset shows the same data on an expanded axis.
Figure 3
Figure 3
Cumulative incidence of HIV-1 infection by pre-specified baseline variables. Cumulative incidence over months 0-24 in the MITT cohort, by sex-at-birth (A) and by age among females (B). Inset shows the same data on an expanded axis.
See this image and copyright information in PMC

Comment in

References

    1. UNAIDS . UNAIDS Fact Sheet 2018. Geneva, Switzerland: 2018.
    1. Human Sciences Research Council . The Fifth South African National HIV Prevalence, Incidence, Behaviour and Communication Survey, 2017: HIV Impact Assessment Summary Report. Cape Town, South Africa: 2018.
    1. Rerks-Ngarm S, Pitisuttithum P, Nitayaphan S, et al. . Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. N Engl J Med 2009;361:2209-20. - PubMed
    1. Gray G, Doherty T, Mohapi L, et al. . HIV research in South Africa: Advancing life. South African Medical Journal 2019;109:36-40. - PubMed
    1. Laher F, Moodie Z, Cohen KW, et al. . Safety and immune responses after a 12-month booster in healthy HIV-uninfected adults in HVTN 100 in South Africa: A randomized double-blind placebo-controlled trial of ALVAC-HIV (vCP2438) and bivalent subtype C gp120/MF59 vaccines. PLoS Med 2020;17:e1003038. - PMC - PubMed

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