Hybrid versus vaccine immunity of mRNA-1273 among people living with HIV in East and Southern Africa: a prospective cohort analysis from the multicentre CoVPN 3008 (Ubuntu) study
Creators: name: Mutuluuza, Cissy Kityo
name: Kee, Jia Jin
name: Inambao, Mubiana
name: Mitha, Essack
name: Kalonji, Dishiki
name: Brumskine, William
name: McElrath, M. Juliana
name: McHarry, Kirsten
name: Wilkinson, Eduan
name: Nuwagaba-Biribonwoha, Harriet
name: Said, Jamil
name: Diacon, Andreas Henri
name: Gill, Katherine Margaret
name: Hudson, Aaron
name: Kassim, Priya
name: Tayob, Mohammed Siddique
name: Miner, Maurine D.
name: Naicker, Vimla
name: Makhema, Joseph
name: Huang, Yunda
name: Elyanu, Peter James
name: Dawson, Rodney
name: Potgieter, Elsje Louise
name: Magaret, Craig A.
name: Nanvubya, Annet
name: Odhiambo, Jackline
name: Moloantoa, Tumelo
name: CoVPN 3008 Ubuntu Study Team
name: Takalani, Azwidihwi
name: Innes, Steve
name: Ferarri, Guido
name: Wabwire, Deo Ogema
name: Mboya, Grace
name: Punt, Zelda
name: Lessells, Richard
name: Fry, Samantha
name: Kasaro, Margaret
name: Coetzer, Soritha
name: Singh, Yashna
name: Chirenje, Zvavahera
name: Badal-Faesen, Sharlaa
name: Otieno, Walter
name: Corey, Lawrence
name: Vahed, Yacoob
name: Yacovone, Margaret
name: Polakowski, Laura
name: Innes, Craig
name: Malahleha, Moelo
name: Potloane, Disebo
name: Dadabhai, Sufia
name: Hural, John
name: Kublin, James G.
name: Villaran, Manuel
name: Kayange, Noel
name: Gilbert, Peter B.
name: Samandari, Taraz
name: Fisher, Leigh H.
name: Naicker, Nivashnee
name: Nchabeleng, Maphoshane
name: Hosseinipour, Mina C.
name: Laher, Fatima
name: Gray, Glenda E.
name: Tapley, Asa
name: Le Roux, Bert
name: Kamuti, Ethel
name: Mda, Pamela
name: Mngadi, Kathryn
name: Garrett, Nigel
name: Maluleke, Vongane Louisa
name: Bekker, Linda-Gail
name: Andriesen, Jessica
name: Shah, Parth
name: Zhang, Bo
name: Andersen-Nissen, Erica
name: Kilembe, William
name: Nana, Anusha
name: de Oliveira, Tulio
name: Kotze, Philip
name: Hoosain, Zaheer Ahmed Ebrahim
name: Mgodi, Nyaradzo M.
name: Delany-Moretlwe, Sinead
Publisher: name: Elsevier
Year: 2025

description: <p>Background With limited access to mRNA COVID-19 vaccines in lower income countries, and people living with HIV (PLWH) largely excluded from clinical trials, Part A of the multicentre CoVPN 3008 (Ubuntu) study aimed to assess the safety of mRNA-1273, the relative effectiveness of hybrid versus vaccine immunity, and SARS-CoV-2 viral persistence among PLWH in East and Southern Africa during the omicron outbreak. Methods Previously unvaccinated adults with HIV and/or other comorbidities associated with severe COVID-19 received either one (hybrid immunity) or two (vaccine immunity) 100-mcg doses of ancestral strain mRNA-1273 in the first month, depending on baseline evidence of prior SARS-CoV-2 infection. In a prospective cohort study design, we used covariate-adjusted Cox regression and counterfactual cumulative incidence methods to determine the hazard ratio and relative risk of COVID-19 and severe COVID-19 with hybrid versus vaccine immunity within six months. The ongoing Ubuntu study is registered on ClinicalTrials.gov (NCT05168813) and this work was conducted from December 2021 to March&nbsp;2023. Findings Between December 2021 and September 2022, 14,237 participants enrolled, and 14,002 (83% PLWH, 69% SARS-CoV-2 seropositive) were included in the analyses. Vaccinations were safe and well tolerated. Common adverse events were pain or tenderness at the injection site (26.7%), headache (20.4%), and malaise (20.3%). Severe adverse events were rare (0.8% of participants after the first and 1.1% after the second vaccination), and none were life-threatening or fatal. Among PLWH, the median CD4 count was 635&nbsp;cells/&mu;l and 18.5% had HIV viraemia. The six-month cumulative incidences in the hybrid immunity and vaccine immunity groups were 2.02% (95% confidence interval [CI] 1.61&ndash;2.44) and 3.40% (95% CI 2.30&ndash;4.49) for COVID-19, and 0.048% (95% CI 0.00&ndash;0.10) and 0.32% (95% CI 0.59&ndash;0.63) for severe COVID-19. Among all PLWH the hybrid immunity group had a 42% lower hazard rate of COVID-19 (hazard ratio [HR] 0.58; 95% CI 0.44&ndash;0.77; p&nbsp;&lt;&nbsp;0.001) and a 73% lower hazard rate of severe COVID-19 (HR 0.27; 95% CI 0.07&ndash;1.04; p&nbsp;=&nbsp;0.056) than the vaccine immunity group, but this effect was not seen among PLWH with CD4 counts &lt;350&nbsp;cells/&mu;l or HIV viraemia. Twenty PLWH had persistent SARS-CoV-2 virus at least 50 days. Interpretation Hybrid immunity was associated with superior protection from COVID-19 compared to vaccine immunity with the ancestral mRNA-1273 vaccine. Persistent infections among immunocompromised PLWH may provide reservoirs for emerging variants. Funding National Institute of Allergy and Infectious Diseases.</p>