EClinicalMedicine (Feb 2025)

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) studyResearch in context

  • Nigel Garrett,
  • Asa Tapley,
  • Aaron Hudson,
  • Sufia Dadabhai,
  • Bo Zhang,
  • Nyaradzo M. Mgodi,
  • Jessica Andriesen,
  • Azwidihwi Takalani,
  • Leigh H. Fisher,
  • Jia Jin Kee,
  • Craig A. Magaret,
  • Manuel Villaran,
  • John Hural,
  • Erica Andersen-Nissen,
  • Guido Ferarri,
  • Maurine D. Miner,
  • Bert Le Roux,
  • Eduan Wilkinson,
  • Richard Lessells,
  • Tulio de Oliveira,
  • Jackline Odhiambo,
  • Parth Shah,
  • Laura Polakowski,
  • Margaret Yacovone,
  • Taraz Samandari,
  • Zvavahera Chirenje,
  • Peter James Elyanu,
  • Joseph Makhema,
  • Ethel Kamuti,
  • Harriet Nuwagaba-Biribonwoha,
  • Sharlaa Badal-Faesen,
  • William Brumskine,
  • Soritha Coetzer,
  • Rodney Dawson,
  • Sinead Delany-Moretlwe,
  • Andreas Henri Diacon,
  • Samantha Fry,
  • Katherine Margaret Gill,
  • Zaheer Ahmed Ebrahim Hoosain,
  • Mina C. Hosseinipour,
  • Mubiana Inambao,
  • Craig Innes,
  • Steve Innes,
  • Dishiki Kalonji,
  • Margaret Kasaro,
  • Priya Kassim,
  • Noel Kayange,
  • William Kilembe,
  • Fatima Laher,
  • Moelo Malahleha,
  • Vongane Louisa Maluleke,
  • Grace Mboya,
  • Kirsten McHarry,
  • Essack Mitha,
  • Kathryn Mngadi,
  • Pamela Mda,
  • Tumelo Moloantoa,
  • Cissy Kityo Mutuluuza,
  • Nivashnee Naicker,
  • Vimla Naicker,
  • Anusha Nana,
  • Annet Nanvubya,
  • Maphoshane Nchabeleng,
  • Walter Otieno,
  • Elsje Louise Potgieter,
  • Disebo Potloane,
  • Zelda Punt,
  • Jamil Said,
  • Yashna Singh,
  • Mohammed Siddique Tayob,
  • Yacoob Vahed,
  • Deo Ogema Wabwire,
  • M. Juliana McElrath,
  • James G. Kublin,
  • Linda-Gail Bekker,
  • Peter B. Gilbert,
  • Lawrence Corey,
  • Glenda E. Gray,
  • Yunda Huang,
  • Philip Kotze,
  • Sharlaa Badal-Faesen,
  • Kagisho Baepanye,
  • Veronique Bailey,
  • Katekani Baloyi-Oseh,
  • Mumtaz Booley,
  • Johannes Louis Botha,
  • Yolande Brown,
  • Valerie Brown,
  • Lisa Bunts,
  • Soritha Coetzer,
  • Myron Cohen,
  • Shirley Collie,
  • Rodney Dawson,
  • Pallabi Deb,
  • Hana El Sahly,
  • Jill El-Khorazaty,
  • Andries Engelbrecht,
  • Marianne Gildea,
  • Dhevium Govender,
  • Jen Hanke,
  • Jayla Harris,
  • Simone Hendricks,
  • Nick Hopkinson,
  • Haley Howell,
  • Nzeera Ketter,
  • Kentse Khuto,
  • Faatima Laher Omar,
  • Leolin Katsidzira,
  • Kim Linton,
  • James Ludwig,
  • Bongile Mabilane,
  • Matshidiso Malefo,
  • Ndiitwani Mamushiana,
  • Daciana Margineantu,
  • Jeanine May,
  • Fatima Mayat,
  • Cindy Molitor,
  • Yeshnee Naidoo,
  • Michelle Nebergall,
  • Alan Nguyen,
  • Sarah Nikles,
  • Bianca Noronha,
  • Melissa Peda,
  • Tamara Phiri,
  • Shanthie Pillay,
  • Sureshnee Pillay,
  • Lori Proulx-Burns,
  • Laurie Rinn,
  • Lisa Sanders,
  • Carrie Sopher,
  • Smitha Sripathy,
  • Michael Stirewalt,
  • Houriiyah Tegally,
  • Sara Thiebaud,
  • Alicia Toledano,
  • Stephanie Van Wyk,
  • Shamaya Whitby,
  • Stephany Wilcox,
  • Eduan Wilkinson,
  • Haven Wilvich,
  • Charles Wiysonge,
  • Nelisiwe Xaba,
  • Ntokozo Xulu

Journal volume & issue
Vol. 80
p. 103054

Abstract

Read online

Summary: 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 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 cells/μl 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] 1.61–2.44) and 3.40% (95% CI 2.30–4.49) for COVID-19, and 0.048% (95% CI 0.00–0.10) and 0.32% (95% CI 0.59–0.63) 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 0.44–0.77; p < 0.001) and a 73% lower hazard rate of severe COVID-19 (HR 0.27; 95% CI 0.07–1.04; p = 0.056) than the vaccine immunity group, but this effect was not seen among PLWH with CD4 counts <350 cells/μl 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.

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