Safety of investigational vaccines against human immunodeficiency virus

1. In this phase 1 randomized controlled trial, urticaria was reported in several participants who received a messenger RNA vaccine against human immunodeficiency virus.

2. Participants with urticaria were more likely to have received the Moderna COVID-19 vaccine compared with participants without urticaria.

Evidence Rating Level: 2 (Good)

Study Rundown: The success of messenger RNA (mRNA) vaccines in reducing COVID-19 morbidity and mortality has prompted the development of similar vaccines for other pathogens, including human immunodeficiency virus (HIV). Although mRNA vaccines are generally safe, adverse events (AEs) have been reported during and after clinical trials, including acute and chronic urticaria. This study aimed to examine the overall safety of a trimer mRNA vaccine against HIV, with particular focus on chronic urticaria as a side-effect. Over three-quarters of participants reported AEs, including lymphadenopathy and chronic urticaria, while over five percent of participants discontinued the trial due to AEs. Improvement after medical treatment was seen in most participants with urticaria, with the most common primary therapy being antihistamines. However, most participants with urticaria reported unresolved symptoms at 12 months. Participants with urticaria were more likely to have only received the Moderna COVID-19 vaccine or had the Moderna vaccine as the last vaccine before recruitment; they were also more likely to have received the Moderna vaccine after recruitment. The generalizability of this study was limited by the small sample size, the lack of a placebo group, and the lack of prospective sample collection. Nonetheless, this study underlined the high incidence of chronic, delayed urticaria following receipt of HIV-1 mRNA vaccines.

Click to read this study in AIM

Relevant Reading: Chronic urticaria after Moderna COVID-19 vaccine boosters: A case series

In-Depth [prospective cohort]: This phase 1 study aimed to analyze the safety profile of an investigational mRNA vaccine series against HIV. Exclusion criteria were receipt of any experimental HIV vaccine, any live attenuated vaccine or mRNA SARS-CoV-2 vaccine within 4 months of enrollment, or any killed, subunit, or inactivated vaccine or any adenoviral-vectored or protein SARS-CoV-2 vaccine within 2 months of enrollment; history of serious reaction to any vaccine; or idiopathic urticaria within the past year. Participants were divided into 6 groups, 3 of whom received the 100-mcg vaccine product and the other 3 the 250-mcg product. The study enrolled 108 participants; all participants received the first dose, while 94 (87%) received the second dose and 87 (81%) the third dose. A total of 190 AEs were reported in 80 (74%) participants, 30 of which were related to the vaccine. The most common AEs were lymphadenopathy (n = 8 in 5 participants) and urticaria (n = 7 in 7 participants). The study was discontinued for 6 participants due to AEs; urticaria had developed in 4 of these participants. Of the 7 (7% [95% CI, 3% to 13%]) participants who developed urticaria, 5 (71%) were in the 100-mcg groups and 2 (29%) in the 250-mcg groups; 2 (29%) participants reported urticaria after the first dose and 5 (71%) after the second dose, although 2 of these 5 participants had developed urticaria after the first dose but did not report it until after the second dose. Chronic urticaria was observed in 5 (71%) participants. Participants with urticaria were more likely to have received the Moderna COVID-19 vaccine (100% [7 of 7; 95% CI, 65% to 100%]) compared with those without urticaria (37% [37 of 101; 95% CI, 28% to 46%]), with an odds ratio [OR] of 12 (95% CI, 2 to 310). Overall, this study reported a high frequency of delayed urticaria in participants who received an mRNA HIV vaccine.

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