The phase 2b-3 trial analyzing the efficacy of the ALVAC–gp120 regimen showed that it did not prevent an HIV-1 infection among the participants in the study at 24 months.
A recent study published in the New England Journal of Medicine has found that the ALVAC–gp120 regimen did not prevent an infection of HIV-1 among participants in South Africa, despite previous evidence of immunogenicity in other trials.
The research was conducted by investigators from the HIV Vaccine Trials Network (HVTN).
An effective and safe vaccine is key to eradicating HIV. After a canarypox–protein HIV vaccine regimen demonstrated a modest efficacy in reducing infection and a similar regimen using HIV-1 subtype C virus showed potent humoral and cellular responses in a phase 1–2a trial in South Africa, investigators sought to increase efficacy and safety data with a larger trial.
“Lacking immunologic markers of protection to guide vaccine development, researchers have predicated large-scale efficacy trials on empirical approaches that seek to identify specific immune responses that are correlated with protection and build on the responses that are associated with even modest vaccine efficacy,” Mark B. Feinberg, MD, said in an editorial that accompanied the study.
The investigators behind the randomized, double-blind, placebo-controlled trial randomly assigned, in a 1:1 ratio, 5,404 participants to receive either the vaccine regimen or a placebo at 14 sites in South Africa. The participants were stratified according to sex and site, with centrally generated randomization by the Statistical Center for HIV–AIDS Research and Prevention (SCHARP). They were between the ages of 18-35 and had no HIV-1 infection.
The regimen consisted of an ALVAC-HIV vector and an MF59-adjuvanted bivalent subtype C gp120, and the trial was designed to evaluate vaccine efficacy to prevent HIV-1 infection within 24 months after enrollment.
Findings from the study showed that during the first 24 months of follow up, 138 HIV-1 infections occurred in the vaccine group and 133 in the placebo group, for an estimated incidence rate of 3.4 per 100 person-years. At 36 months follow up, the incidence of HIV-1 infection was similar in the vaccine group and the placebo group
Additional findings showed that between randomization and month 24, vaccine efficacy according to sex was similar in the two groups, with an estimated hazard ratio of 1.03 for women and 0.99 for men.
“Despite promising immunogenicity, this canarypox–protein HIV vaccine regimen was not efficacious in preventing the acquisition of HIV-1 infection in our trial population in South Africa,” the author wrote. “The high HIV-1 incidence that we observed in our trial illustrates the unrelenting aspect of the epidemic, especially among young women. More than ever, an effective vaccine to prevent HIV-1 acquisition in diverse populations is needed.”