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

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

doi:10.1016/j.eclinm.2024.103054

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

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 OliveiraJackline 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

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Article number	103054
Journal	EClinicalMedicine
Volume	80
DOIs	https://doi.org/10.1016/j.eclinm.2024.103054
Publication status	Published - Feb 2025
Externally published	Yes

Keywords

COVID-19
Hybrid immunity
People living with HIV
SARS-CoV-2
Vaccine immunity
mRNA-1273

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.eclinm.2024.103054

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Garrett, N., Tapley, A., Hudson, A., Dadabhai, S., Zhang, B., Mgodi, N. M., Andriesen, J., Takalani, A., Fisher, L. H., Kee, J. J., Magaret, C. A., Villaran, M., Hural, J., Andersen-Nissen, E., Ferarri, G., Miner, M. D., Le Roux, B., Wilkinson, E., Lessells, R., ... Kotze, P. (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) study. EClinicalMedicine, 80, Article 103054. https://doi.org/10.1016/j.eclinm.2024.103054

@article{5888553f022b435395c342a20da2edb7,

title = "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",

abstract = "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.",

keywords = "COVID-19, Hybrid immunity, People living with HIV, SARS-CoV-2, Vaccine immunity, mRNA-1273",

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

note = "Publisher Copyright: {\textcopyright} 2025 The Authors",

year = "2025",

month = feb,

doi = "10.1016/j.eclinm.2024.103054",

language = "English",

volume = "80",

journal = "EClinicalMedicine",

issn = "2589-5370",

publisher = "Elsevier Ltd.",

}

Garrett, N, Tapley, A, Hudson, A, Dadabhai, S, Zhang, B, Mgodi, NM, Andriesen, J, Takalani, A, Fisher, LH, Kee, JJ, Magaret, CA, Villaran, M, Hural, J, Andersen-Nissen, E, Ferarri, G, Miner, MD, Le Roux, B, Wilkinson, E, Lessells, R, de Oliveira, T, Odhiambo, J, Shah, P, Polakowski, L, Yacovone, M, Samandari, T, Chirenje, Z, Elyanu, PJ, Makhema, J, Kamuti, E, Nuwagaba-Biribonwoha, H, Badal-Faesen, S, Brumskine, W, Coetzer, S, Dawson, R, Delany-Moretlwe, S, Diacon, AH, Fry, S, Gill, KM, Ebrahim Hoosain, ZA, Hosseinipour, MC, Inambao, M, Innes, C, Innes, S, Kalonji, D, Kasaro, M, Kassim, P, Kayange, N, Kilembe, W, Laher, F, Malahleha, M, Maluleke, VL, Mboya, G, McHarry, K, Mitha, E, Mngadi, K, Mda, P, Moloantoa, T, Mutuluuza, CK, Naicker, N, Naicker, V, Nana, A, Nanvubya, A, Nchabeleng, M, Otieno, W, Potgieter, EL, Potloane, D, Punt, Z, Said, J, Singh, Y, Tayob, MS, Vahed, Y, Wabwire, DO, McElrath, MJ, Kublin, JG, Bekker, LG, Gilbert, PB, Corey, L, Gray, GE, Huang, Y & Kotze, P 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) study', EClinicalMedicine, vol. 80, 103054. https://doi.org/10.1016/j.eclinm.2024.103054

TY - JOUR

T1 - Hybrid versus vaccine immunity of mRNA-1273 among people living with HIV in East and Southern Africa

T2 - a prospective cohort analysis from the multicentre CoVPN 3008 (Ubuntu) study

AU - Garrett, Nigel

AU - Tapley, Asa

AU - Hudson, Aaron

AU - Dadabhai, Sufia

AU - Zhang, Bo

AU - Mgodi, Nyaradzo M.

AU - Andriesen, Jessica

AU - Takalani, Azwidihwi

AU - Fisher, Leigh H.

AU - Kee, Jia Jin

AU - Magaret, Craig A.

AU - Villaran, Manuel

AU - Hural, John

AU - Andersen-Nissen, Erica

AU - Ferarri, Guido

AU - Miner, Maurine D.

AU - Le Roux, Bert

AU - Wilkinson, Eduan

AU - Lessells, Richard

AU - de Oliveira, Tulio

AU - Odhiambo, Jackline

AU - Shah, Parth

AU - Polakowski, Laura

AU - Yacovone, Margaret

AU - Samandari, Taraz

AU - Chirenje, Zvavahera

AU - Elyanu, Peter James

AU - Makhema, Joseph

AU - Kamuti, Ethel

AU - Nuwagaba-Biribonwoha, Harriet

AU - Badal-Faesen, Sharlaa

AU - Brumskine, William

AU - Coetzer, Soritha

AU - Dawson, Rodney

AU - Delany-Moretlwe, Sinead

AU - Diacon, Andreas Henri

AU - Fry, Samantha

AU - Gill, Katherine Margaret

AU - Ebrahim Hoosain, Zaheer Ahmed

AU - Hosseinipour, Mina C.

AU - Inambao, Mubiana

AU - Innes, Craig

AU - Innes, Steve

AU - Kalonji, Dishiki

AU - Kasaro, Margaret

AU - Kassim, Priya

AU - Kayange, Noel

AU - Kilembe, William

AU - Laher, Fatima

AU - Malahleha, Moelo

AU - Maluleke, Vongane Louisa

AU - Mboya, Grace

AU - McHarry, Kirsten

AU - Mitha, Essack

AU - Mngadi, Kathryn

AU - Mda, Pamela

AU - Moloantoa, Tumelo

AU - Mutuluuza, Cissy Kityo

AU - Naicker, Nivashnee

AU - Naicker, Vimla

AU - Nana, Anusha

AU - Nanvubya, Annet

AU - Nchabeleng, Maphoshane

AU - Otieno, Walter

AU - Potgieter, Elsje Louise

AU - Potloane, Disebo

AU - Punt, Zelda

AU - Said, Jamil

AU - Singh, Yashna

AU - Tayob, Mohammed Siddique

AU - Vahed, Yacoob

AU - Wabwire, Deo Ogema

AU - McElrath, M. Juliana

AU - Kublin, James G.

AU - Bekker, Linda Gail

AU - Gilbert, Peter B.

AU - Corey, Lawrence

AU - Gray, Glenda E.

AU - Huang, Yunda

AU - Kotze, Philip

PY - 2025/2

Y1 - 2025/2

N2 - 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.

AB - 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.

KW - COVID-19

KW - Hybrid immunity

KW - People living with HIV

KW - SARS-CoV-2

KW - Vaccine immunity

KW - mRNA-1273

UR - http://www.scopus.com/inward/record.url?scp=85215392427&partnerID=8YFLogxK

U2 - 10.1016/j.eclinm.2024.103054

DO - 10.1016/j.eclinm.2024.103054

M3 - Article

C2 - 39902315

AN - SCOPUS:85215392427

SN - 2589-5370

VL - 80

JO - EClinicalMedicine

JF - EClinicalMedicine

M1 - 103054

ER -

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

Abstract

Keywords

UN SDGs

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