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Safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 in people living with and without HIV in South Africa: an interim analysis of a randomised, double-blind, placebo-controlled, phase 1B/2A trial.
Lancet HIV. 2021 09; 8(9):e568-e580.LH

Abstract

BACKGROUND

People living with HIV are at an increased risk of fatal outcome when admitted to hospital for severe COVID-19 compared with HIV-negative individuals. We aimed to assess safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine in people with HIV and HIV-negative individuals in South Africa.

METHODS

In this ongoing, double-blind, placebo-controlled, phase 1B/2A trial (COV005), people with HIV and HIV-negative participants aged 18-65 years were enrolled at seven South African locations and were randomly allocated (1:1) with full allocation concealment to receive a prime-boost regimen of ChAdOx1 nCoV-19, with two doses given 28 days apart. Eligibility criteria for people with HIV included being on antiretroviral therapy for at least 3 months, with a plasma HIV viral load of less than 1000 copies per mL. In this interim analysis, safety and reactogenicity was assessed in all individuals who received at least one dose of ChAdOx1 nCov 19 between enrolment and Jan 15, 2021. Primary immunogenicity analyses included participants who received two doses of trial intervention and were SARS-CoV-2 seronegative at baseline. This trial is registered with ClinicalTrials.gov, NCT04444674, and the Pan African Clinicals Trials Registry, PACTR202006922165132.

FINDINGS

Between June 24 and Nov 12, 2020, 104 people with HIV and 70 HIV-negative individuals were enrolled. 102 people with HIV (52 vaccine; 50 placebo) and 56 HIV-negative participants (28 vaccine; 28 placebo) received the priming dose, 100 people with HIV (51 vaccine; 49 placebo) and 46 HIV-negative participants (24 vaccine; 22 placebo) received two doses (priming and booster). In participants seronegative for SARS-CoV-2 at baseline, there were 164 adverse events in those with HIV (86 vaccine; 78 placebo) and 237 in HIV-negative participants (95 vaccine; 142 placebo). Of seven serious adverse events, one severe fever in a HIV-negative participant was definitely related to trial intervention and one severely elevated alanine aminotranferase in a participant with HIV was unlikely related; five others were deemed unrelated. One person with HIV died (unlikely related). People with HIV and HIV-negative participants showed vaccine-induced serum IgG responses against wild-type Wuhan-1 Asp614Gly (also known as D614G). For participants seronegative for SARS-CoV-2 antigens at baseline, full-length spike geometric mean concentration (GMC) at day 28 was 163·7 binding antibody units (BAU)/mL (95% CI 89·9-298·1) for people with HIV (n=36) and 112·3 BAU/mL (61·7-204·4) for HIV-negative participants (n=23), with a rising day 42 GMC booster response in both groups. Baseline SARS-CoV-2 seropositive people with HIV demonstrated higher antibody responses after each vaccine dose than did people with HIV who were seronegative at baseline. High-level binding antibody cross-reactivity for the full-length spike and receptor-binding domain of the beta variant (B.1.351) was seen regardless of HIV status. In people with HIV who developed high titre responses, predominantly those who were receptor-binding domain seropositive at enrolment, neutralising activity against beta was retained.

INTERPRETATION

ChAdOx1 nCoV-19 was well tolerated, showing favourable safety and immunogenicity in people with HIV, including heightened immunogenicity in SARS-CoV-2 baseline-seropositive participants. People with HIV showed cross-reactive binding antibodies to the beta variant and Asp614Gly wild-type, and high responders retained neutralisation against beta.

FUNDING

The Bill & Melinda Gates Foundation, South African Medical Research Council, UK Research and Innovation, UK National Institute for Health Research, and the South African Medical Research Council.

Authors+Show Affiliations

South African Medical Research Council Vaccines and Infectious Diseases Analytics Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; Department of Science and Innovation/National Research Foundation South African Research Chair Initiative in Vaccine Preventable Diseases Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; African Leadership in Vaccinology Expertise, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. Electronic address: shabir.madhi@wits.ac.za.South African Medical Research Council Vaccines and Infectious Diseases Analytics Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; Department of Science and Innovation/National Research Foundation South African Research Chair Initiative in Vaccine Preventable Diseases Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.South African Medical Research Council Vaccines and Infectious Diseases Analytics Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; Department of Science and Innovation/National Research Foundation South African Research Chair Initiative in Vaccine Preventable Diseases Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; African Leadership in Vaccinology Expertise, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.African Leadership in Vaccinology Expertise, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; Wits Reproductive Health and HIV Institute, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.African Leadership in Vaccinology Expertise, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.South African Medical Research Council Vaccines and Infectious Diseases Analytics Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; Department of Science and Innovation/National Research Foundation South African Research Chair Initiative in Vaccine Preventable Diseases Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.Setshaba Research Centre, Tshwane, South Africa.Division of Pulmonology, Groote Schuur Hospital and the University of Cape Town, Cape Town, South Africa; Faculty of Infectious and Tropical Diseases, Department of Immunology and Infection, London School of Hygiene & Tropical Medicine, London, UK.Family Centre for Research With Ubuntu, Department of Paediatrics, University of Stellenbosch, Cape Town, South Africa.Soweto Clinical Trials Centre, Soweto, South Africa.Perinatal HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.Oxford Vaccine Group, University of Oxford, Oxford, UK; Department of Paediatrics, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford, UK.South African Medical Research Council Vaccines and Infectious Diseases Analytics Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; Department of Science and Innovation/National Research Foundation South African Research Chair Initiative in Vaccine Preventable Diseases Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.SAMRC Antibody Immunity Research Unit, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; National Institute for Communicable Diseases Division of the National Health Laboratory Service, Johannesburg, South Africa.Wits Reproductive Health and HIV Institute, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.South African Medical Research Council Vaccines and Infectious Diseases Analytics Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; Department of Science and Innovation/National Research Foundation South African Research Chair Initiative in Vaccine Preventable Diseases Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.SAMRC Antibody Immunity Research Unit, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; National Institute for Communicable Diseases Division of the National Health Laboratory Service, Johannesburg, South Africa.Jenner Institute, Nuffield Department of Medicine, University of Oxford, UK.Wits Reproductive Health and HIV Institute, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.Setshaba Research Centre, Tshwane, South Africa.SAMRC Antibody Immunity Research Unit, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; National Institute for Communicable Diseases Division of the National Health Laboratory Service, Johannesburg, South Africa.South African Medical Research Council Vaccines and Infectious Diseases Analytics Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; Department of Science and Innovation/National Research Foundation South African Research Chair Initiative in Vaccine Preventable Diseases Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.South African Medical Research Council Vaccines and Infectious Diseases Analytics Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; Department of Science and Innovation/National Research Foundation South African Research Chair Initiative in Vaccine Preventable Diseases Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.SAMRC Antibody Immunity Research Unit, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; National Institute for Communicable Diseases Division of the National Health Laboratory Service, Johannesburg, South Africa.South African Medical Research Council Vaccines and Infectious Diseases Analytics Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; Department of Science and Innovation/National Research Foundation South African Research Chair Initiative in Vaccine Preventable Diseases Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.South African Medical Research Council Vaccines and Infectious Diseases Analytics Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; Department of Science and Innovation/National Research Foundation South African Research Chair Initiative in Vaccine Preventable Diseases Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.Wits Reproductive Health and HIV Institute, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.Oxford Vaccine Group, University of Oxford, Oxford, UK; Department of Paediatrics, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford, UK.South African Medical Research Council Vaccines and Infectious Diseases Analytics Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; Department of Science and Innovation/National Research Foundation South African Research Chair Initiative in Vaccine Preventable Diseases Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.South African Medical Research Council Vaccines and Infectious Diseases Analytics Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; Department of Science and Innovation/National Research Foundation South African Research Chair Initiative in Vaccine Preventable Diseases Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.Wits Reproductive Health and HIV Institute, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.Oxford Vaccine Group, University of Oxford, Oxford, UK; Department of Paediatrics, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford, UK.AstraZeneca Biopharmaceuticals, Cambridge, UK.AstraZeneca Biopharmaceuticals, Cambridge, UK.Jenner Institute, Nuffield Department of Medicine, University of Oxford, UK.Oxford Vaccine Group, University of Oxford, Oxford, UK; Department of Paediatrics, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford, UK.SAMRC Antibody Immunity Research Unit, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; National Institute for Communicable Diseases Division of the National Health Laboratory Service, Johannesburg, South Africa.South African Medical Research Council Vaccines and Infectious Diseases Analytics Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; Department of Science and Innovation/National Research Foundation South African Research Chair Initiative in Vaccine Preventable Diseases Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; African Leadership in Vaccinology Expertise, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.No affiliation info available

Pub Type(s)

Clinical Trial, Phase I
Clinical Trial, Phase II
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

34416193

Citation

Madhi, Shabir A., et al. "Safety and Immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) Vaccine Against SARS-CoV-2 in People Living With and Without HIV in South Africa: an Interim Analysis of a Randomised, Double-blind, Placebo-controlled, Phase 1B/2A Trial." The Lancet. HIV, vol. 8, no. 9, 2021, pp. e568-e580.
Madhi SA, Koen AL, Izu A, et al. Safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 in people living with and without HIV in South Africa: an interim analysis of a randomised, double-blind, placebo-controlled, phase 1B/2A trial. Lancet HIV. 2021;8(9):e568-e580.
Madhi, S. A., Koen, A. L., Izu, A., Fairlie, L., Cutland, C. L., Baillie, V., Padayachee, S. D., Dheda, K., Barnabas, S. L., Bhorat, Q. E., Briner, C., Aley, P. K., Bhikha, S., Hermanus, T., Horne, E., Jose, A., Kgagudi, P., Lambe, T., Masenya, M., ... Kwatra, G. (2021). Safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 in people living with and without HIV in South Africa: an interim analysis of a randomised, double-blind, placebo-controlled, phase 1B/2A trial. The Lancet. HIV, 8(9), e568-e580. https://doi.org/10.1016/S2352-3018(21)00157-0
Madhi SA, et al. Safety and Immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) Vaccine Against SARS-CoV-2 in People Living With and Without HIV in South Africa: an Interim Analysis of a Randomised, Double-blind, Placebo-controlled, Phase 1B/2A Trial. Lancet HIV. 2021;8(9):e568-e580. PubMed PMID: 34416193.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 in people living with and without HIV in South Africa: an interim analysis of a randomised, double-blind, placebo-controlled, phase 1B/2A trial. AU - Madhi,Shabir A, AU - Koen,Anthonet L, AU - Izu,Alane, AU - Fairlie,Lee, AU - Cutland,Clare L, AU - Baillie,Vicky, AU - Padayachee,Sherman D, AU - Dheda,Keertan, AU - Barnabas,Shaun L, AU - Bhorat,Qasim Ebrahim, AU - Briner,Carmen, AU - Aley,Parvinder K, AU - Bhikha,Sutika, AU - Hermanus,Tandile, AU - Horne,Elizea, AU - Jose,Aylin, AU - Kgagudi,Prudence, AU - Lambe,Teresa, AU - Masenya,Masebole, AU - Masilela,Mduduzi, AU - Mkhize,Nonhlanhla, AU - Moultrie,Andrew, AU - Mukendi,Christian K, AU - Moyo-Gwete,Thandeka, AU - Nana,Amit J, AU - Nzimande,Ayanda, AU - Patel,Faeezah, AU - Rhead,Sarah, AU - Taoushanis,Carol, AU - Thombrayil,Asha, AU - van Eck,Samuel, AU - Voysey,Merryn, AU - Villafana,Tonya L, AU - Vekemans,Johan, AU - Gilbert,Sarah C, AU - Pollard,Andrew J, AU - Moore,Penny L, AU - Kwatra,Gaurav, AU - ,, Y1 - 2021/08/17/ PY - 2021/05/17/received PY - 2021/07/02/revised PY - 2021/07/05/accepted PY - 2021/8/21/pubmed PY - 2021/9/16/medline PY - 2021/8/20/entrez SP - e568 EP - e580 JF - The lancet. HIV JO - Lancet HIV VL - 8 IS - 9 N2 - BACKGROUND: People living with HIV are at an increased risk of fatal outcome when admitted to hospital for severe COVID-19 compared with HIV-negative individuals. We aimed to assess safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine in people with HIV and HIV-negative individuals in South Africa. METHODS: In this ongoing, double-blind, placebo-controlled, phase 1B/2A trial (COV005), people with HIV and HIV-negative participants aged 18-65 years were enrolled at seven South African locations and were randomly allocated (1:1) with full allocation concealment to receive a prime-boost regimen of ChAdOx1 nCoV-19, with two doses given 28 days apart. Eligibility criteria for people with HIV included being on antiretroviral therapy for at least 3 months, with a plasma HIV viral load of less than 1000 copies per mL. In this interim analysis, safety and reactogenicity was assessed in all individuals who received at least one dose of ChAdOx1 nCov 19 between enrolment and Jan 15, 2021. Primary immunogenicity analyses included participants who received two doses of trial intervention and were SARS-CoV-2 seronegative at baseline. This trial is registered with ClinicalTrials.gov, NCT04444674, and the Pan African Clinicals Trials Registry, PACTR202006922165132. FINDINGS: Between June 24 and Nov 12, 2020, 104 people with HIV and 70 HIV-negative individuals were enrolled. 102 people with HIV (52 vaccine; 50 placebo) and 56 HIV-negative participants (28 vaccine; 28 placebo) received the priming dose, 100 people with HIV (51 vaccine; 49 placebo) and 46 HIV-negative participants (24 vaccine; 22 placebo) received two doses (priming and booster). In participants seronegative for SARS-CoV-2 at baseline, there were 164 adverse events in those with HIV (86 vaccine; 78 placebo) and 237 in HIV-negative participants (95 vaccine; 142 placebo). Of seven serious adverse events, one severe fever in a HIV-negative participant was definitely related to trial intervention and one severely elevated alanine aminotranferase in a participant with HIV was unlikely related; five others were deemed unrelated. One person with HIV died (unlikely related). People with HIV and HIV-negative participants showed vaccine-induced serum IgG responses against wild-type Wuhan-1 Asp614Gly (also known as D614G). For participants seronegative for SARS-CoV-2 antigens at baseline, full-length spike geometric mean concentration (GMC) at day 28 was 163·7 binding antibody units (BAU)/mL (95% CI 89·9-298·1) for people with HIV (n=36) and 112·3 BAU/mL (61·7-204·4) for HIV-negative participants (n=23), with a rising day 42 GMC booster response in both groups. Baseline SARS-CoV-2 seropositive people with HIV demonstrated higher antibody responses after each vaccine dose than did people with HIV who were seronegative at baseline. High-level binding antibody cross-reactivity for the full-length spike and receptor-binding domain of the beta variant (B.1.351) was seen regardless of HIV status. In people with HIV who developed high titre responses, predominantly those who were receptor-binding domain seropositive at enrolment, neutralising activity against beta was retained. INTERPRETATION: ChAdOx1 nCoV-19 was well tolerated, showing favourable safety and immunogenicity in people with HIV, including heightened immunogenicity in SARS-CoV-2 baseline-seropositive participants. People with HIV showed cross-reactive binding antibodies to the beta variant and Asp614Gly wild-type, and high responders retained neutralisation against beta. FUNDING: The Bill & Melinda Gates Foundation, South African Medical Research Council, UK Research and Innovation, UK National Institute for Health Research, and the South African Medical Research Council. SN - 2352-3018 UR - https://www.unboundmedicine.com/medline/citation/34416193/Safety_and_immunogenicity_of_the_ChAdOx1_nCoV_19__AZD1222__vaccine_against_SARS_CoV_2_in_people_living_with_and_without_HIV_in_South_Africa:_an_interim_analysis_of_a_randomised_double_blind_placebo_controlled_phase_1B/2A_trial_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S2352-3018(21)00157-0 DB - PRIME DP - Unbound Medicine ER -