An Expansion of Weight Inclusivity to Include Body Autonomy and Harm Reduction: Striving for Health Equity.

A key challenge in developing an effective HIV-1 vaccine is the high genetic diversity of HIV-1 across populations due to the high mutation rate and recombination potential during viral replication. Only one HIV-1 vaccine trial, RV144, has shown statistically significant, but modest, vaccine efficacy (31·2% at 3·5 years) in reducing the risk of acquiring HIV; this was insufficient for licensure. Subsequent trials have evaluated other vaccine regimens without demonstrating efficacy. Computationally designed mosaic antigens were developed to provide immunological coverage against various global HIV-1 strains. The vaccine regimen evaluated in this study was derived and refined through a series of preclinical and early phase clinical studies. The phase 1/2a ASCENT trial investigated a heterologous vaccine regimen consisting of a tetravalent adenovirus serotype 26 (Ad26)-based vaccine encoding two mosaic Env antigens and two mosaic Gag–Pol antigens (Ad26.Mos4.HIV) and a bivalent combination of an aluminium phosphate-adjuvanted clade C glycoprotein (gp) 140 and an aluminium phosphate-adjuvanted mosaic gp140. The regimen increased the breadth, magnitude, and durability of binding antibodies to cross-clade panels of Env antigens compared with a single-valent clade C gp140 regimen, without compromising responses against clade C. The magnitude and response rate of CD4 cell responses to Env were also statistically significantly higher with the bivalent clade C–mosaic gp140 regimen versus the single-valent clade C gp140 regimen. The clinical safety and immunogenicity data from ASCENT provided the basis to advance the Ad26.Mos4.HIV and bivalent clade C–mosaic gp140 regimen to this phase 3 study (HVTN 706/HPX3002/Mosaico), which enrolled cisgender men who have sex with men and transgender individuals in Europe, the USA, and Latin America. Clade B is the predominant HIV-1 subtype in these regions. A complementary study to Mosaico, the phase 2b HVTN 705/HPX2008/Imbokodo trial, evaluated a similar vaccine regimen (Ad26.Mos4.HIV/clade C gp140) in young women with increased likelihood of acquiring HIV in southern Africa, where clade C is most prevalent. The vaccine regimen was safe and well tolerated, but did not show efficacy in preventing HIV-1. Imbokodo was ongoing at the time Mosaico completed recruitment and, although Imbokodo showed no benefit, the independent data and safety monitoring board (DSMB) for Mosaico advised the funders to continue the study. This recommendation was based on key differences in vaccine composition, study population, geographical region, circulating HIV-1 clades, use of pre-exposure prophylaxis (PrEP), and mode of transmission (mainly intravaginal intrarectal) between the two trials. We report the primary efficacy, safety, and immunogenicity results of the Mosaico study.