CTN 328: immunogenicity outcomes in people living with HIV in Canada following vaccination for COVID-19 (HIV-COV): protocol for an observational cohort study

Cecilia T Costiniuk; Joel Singer; Marc-André Langlois; Iva Kulic; Judy Needham; Ann Burchell; Mohammad-Ali Jenabian; Sharon Walmsley; Mario Ostrowski; Colin Kovacs; Darrell Tan; Marianne Harris; Mark Hull; Zabrina Brumme; Mark Brockman; Shari Margolese; Enrico Mandarino; Jonathan B Angel; Jean-Pierre Routy; Aslam H Anis; Curtis Cooper

doi:10.1136/bmjopen-2021-054208

CTN 328: immunogenicity outcomes in people living with HIV in Canada following vaccination for COVID-19 (HIV-COV): protocol for an observational cohort study

BMJ Open. 2021 Dec 16;11(12):e054208. doi: 10.1136/bmjopen-2021-054208.

Authors

Cecilia T Costiniuk¹, Joel Singer^{2

3}, Marc-André Langlois⁴, Iva Kulic², Judy Needham², Ann Burchell^{5

6}, Mohammad-Ali Jenabian⁷, Sharon Walmsley⁸, Mario Ostrowski^{9

10}, Colin Kovacs¹¹, Darrell Tan^{12

13}, Marianne Harris¹⁴, Mark Hull¹⁴, Zabrina Brumme^{14

15}, Mark Brockman^{14

15}, Shari Margolese¹⁶, Enrico Mandarino¹⁶, Jonathan B Angel¹⁷, Jean-Pierre Routy¹⁸, Aslam H Anis^{2

3}, Curtis Cooper¹⁹

Affiliations

¹ Department of Medicine, Division of Infectious Diseases and Chronic Viral Illness Service, McGill University Health Centre; Infectious Diseases and Immunity in Global Health Program, Research Institute of the McGill University Health Centre, Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada cecilia.costiniuk@mcgill.ca.
² Canadian Institutes of Health Research (CIHR)--Canadian HIV Trials Network and Centre for Health Evaluation and Outcome Sciences, St. Paul's Hospital, Vancouver, British Columbia, Canada.
³ School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada.
⁴ Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.
⁵ Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
⁶ Department of Family and Community Medicine, St Michael's Hospital, Unity Health Toronto, Toronto, Ontario, Ontario, Canada.
⁷ Department of Biological Sciences and CERMO-FC Research Centre, Université du Québec à Montréal (UQAM), Montreal, Quebec, Canada.
⁸ Department of Medicine, Division of Infectious Diseases, Toronto General Hospital, Toronto, Ontario, Canada.
⁹ Clinical Sciences Division and Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
¹⁰ Department of Medicine, Division of Infectious Diseases, St. Michael's Hospital, Toronto, Ontario, Canada.
¹¹ Maple Leaf Medical Clinic, Toronto, Ontario, Canada.
¹² Department of Medicine, Division of Infectious Diseases, University of Toronto, Montreal, Ontario, Canada.
¹³ MAP Centre for Urban Health Solutions, St. Michael's Hospital, Toronto, Ontario, Canada.
¹⁴ Brisith Columbia Centre for Excellence in HIV/AIDS, Vancouver, British Columbia, Canada.
¹⁵ Faculty of Health Sciences, Simon Fraser University, Burnaby, British Columbia, Canada.
¹⁶ Community Advisory Committee, CIHR Canadian HIV Trials Network, Vancouver, British Columbia, Canada.
¹⁷ Department of Medicine, Division of Infectious Diseases, The Ottawa Hospital, The Ottawa Hospital Research Institute and Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.
¹⁸ Department of Medicine, Division of Hematology and Chronic Viral Illness Service, McGill University Health Centre, Infectious Diseases and Immunity in Global Health Program, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
¹⁹ Department of Medicine, Division of Infectious Diseases, The Ottawa Hospital, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.

Abstract

Introduction: Most existing vaccines require higher or additional doses or adjuvants to provide similar protection for people living with HIV (PLWH) compared with HIV-uninfected individuals. Additional research is necessary to inform COVID-19 vaccine use in PLWH.

Methods and analysis: This multicentred observational Canadian cohort study will enrol 400 PLWH aged >16 years from Montreal, Ottawa, Toronto and Vancouver. Subpopulations of PLWH of interest will include individuals: (1) >55 years of age; (2) with CD4 counts <350 cells/mm³; (3) with multimorbidity (>2 comorbidities) and (4) 'stable' or 'reference' PLWH (CD4 T cells >350 cells/mm³, suppressed viral load for >6 months and <1 comorbidity). Data for 1000 HIV-negative controls will be obtained via a parallel cohort study (Stop the Spread Ottawa), using similar time points and methods. Participants receiving >1 COVID-19 vaccine will attend five visits: prevaccination; 1 month following the first vaccine dose; and at 3, 6 and 12 months following the second vaccine dose. The primary end point will be the percentage of PLWH with COVID-19-specific antibodies at 6 months following the second vaccine dose. Humoral and cell-mediated immune responses, and the interplay between T cell phenotypes and inflammatory markers, will be described. Regression techniques will be used to compare COVID-19-specific immune responses to determine whether there are differences between the 'unstable' PLWH group (CD4 <350 cells/mm3), the stable PLWH cohort and the HIV-negative controls, adjusting for factors believed to be associated with immune response. Unadjusted analyses will reveal whether there are differences in driving factors associated with group membership.

Ethics and dissemination: Research ethics boards at all participating institutions have granted ethics approval for this study. Written informed consent will be obtained from all study participants prior to enrolment. The findings will inform the design of future COVID-19 clinical trials, dosing strategies aimed to improve immune responses and guideline development for PLWH.

Trial registration number: NCT04894448.

Keywords: COVID-19; HIV & AIDS; immunology; virology.

Publication types

Clinical Trial Protocol
Research Support, Non-U.S. Gov't

MeSH terms

COVID-19 Vaccines
COVID-19*
Canada
Cohort Studies
Diterpenes
HIV Infections*
Humans
Multicenter Studies as Topic
Observational Studies as Topic
SARS-CoV-2
Vaccination

Substances

COVID-19 Vaccines
Diterpenes

Associated data

ClinicalTrials.gov/NCT04894448