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Trials Network and Michael Smith Health Research BC (MSHR-BC)","award":["GA2-177713"],"award-info":[{"award-number":["GA2-177713"]}]},{"name":"Canadian Institutes of Health Research (CIHR) Canadian HIV Trials Network and Michael Smith Health Research BC (MSHR-BC)","award":["FRN-175622"],"award-info":[{"award-number":["FRN-175622"]}]},{"name":"Canadian Institutes of Health Research (CIHR) Canadian HIV Trials Network and Michael Smith Health Research BC (MSHR-BC)","award":["DEL-15-006"],"award-info":[{"award-number":["DEL-15-006"]}]},{"name":"Canadian Institutes of Health Research (CIHR) Canadian HIV Trials Network and Michael Smith Health Research BC (MSHR-BC)","award":["107752\/Z\/15\/Z"],"award-info":[{"award-number":["107752\/Z\/15\/Z"]}]},{"name":"Sub-Saharan African Network for TB\/HIV Research Excellence (SANTHE), a DELTAS Africa Initiative","award":["2020-HQ-000120"],"award-info":[{"award-number":["2020-HQ-000120"]}]},{"name":"Sub-Saharan African Network for TB\/HIV Research Excellence (SANTHE), a DELTAS Africa Initiative","award":["GA2-177713"],"award-info":[{"award-number":["GA2-177713"]}]},{"name":"Sub-Saharan African Network for TB\/HIV Research Excellence (SANTHE), a DELTAS Africa Initiative","award":["FRN-175622"],"award-info":[{"award-number":["FRN-175622"]}]},{"name":"Sub-Saharan African Network for TB\/HIV Research Excellence (SANTHE), a DELTAS Africa Initiative","award":["DEL-15-006"],"award-info":[{"award-number":["DEL-15-006"]}]},{"name":"Sub-Saharan African Network for TB\/HIV Research Excellence (SANTHE), a DELTAS Africa Initiative","award":["107752\/Z\/15\/Z"],"award-info":[{"award-number":["107752\/Z\/15\/Z"]}]},{"name":"Wellcome Trust","award":["2020-HQ-000120"],"award-info":[{"award-number":["2020-HQ-000120"]}]},{"name":"Wellcome Trust","award":["GA2-177713"],"award-info":[{"award-number":["GA2-177713"]}]},{"name":"Wellcome Trust","award":["FRN-175622"],"award-info":[{"award-number":["FRN-175622"]}]},{"name":"Wellcome 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Accumulating evidence indicates that PLWH, particularly those receiving antiretroviral therapy, mount strong antibody responses to COVID-19 vaccines, but fewer studies have examined cellular immune responses to the vaccinations. Here, we used an activation-induced marker (AIM) assay to quantify SARS-CoV-2 spike-specific CD4+ and CD8+ T cells generated by two and three doses of COVID-19 vaccines in 50 PLWH receiving antiretroviral therapy, compared to 87 control participants without HIV. In a subset of PLWH, T-cell responses were also assessed after post-vaccine breakthrough infections and\/or receipt of a fourth vaccine dose. All participants remained SARS-CoV-2 infection-naive until at least one month after their third vaccine dose. SARS-CoV-2 infection was determined by seroconversion to a Nucleocapsid (N) antigen, which occurred in 21 PLWH and 38 control participants after the third vaccine dose. Multivariable regression analyses were used to investigate the relationships between sociodemographic, health- and vaccine-related variables, vaccine-induced T-cell responses, and breakthrough infection risk. We observed that a third vaccine dose boosted spike-specific CD4+ and CD8+ T-cell frequencies significantly above those measured after the second dose (all p &lt; 0.0001). Median T-cell frequencies did not differ between PLWH and controls after the second dose (p &gt; 0.1), but CD8+ T-cell responses were modestly lower in PLWH after the third dose (p = 0.02), an observation that remained significant after adjusting for sociodemographic, health- and vaccine-related variables (p = 0.045). In PLWH who experienced a breakthrough infection, median T-cell frequencies increased even higher than those observed after three vaccine doses (p &lt; 0.03), and CD8+ T-cell responses in this group remained higher even after a fourth vaccine dose (p = 0.03). In multivariable analyses, the only factor associated with an increased breakthrough infection risk was younger age, which is consistent with the rapid increase in SARS-CoV-2 seropositivity that was seen among younger adults in Canada after the initial appearance of the Omicron variant. These results indicate that PLWH receiving antiretroviral therapy mount strong T-cell responses to COVID-19 vaccines that can be enhanced by booster doses or breakthrough infection.<\/jats:p>","DOI":"10.3390\/v16050661","type":"journal-article","created":{"date-parts":[[2024,4,24]],"date-time":"2024-04-24T10:18:36Z","timestamp":1713953916000},"page":"661","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["T-Cell Responses to COVID-19 Vaccines and Breakthrough Infection in People Living with HIV Receiving Antiretroviral Therapy"],"prefix":"10.3390","volume":"16","author":[{"given":"Sneha","family":"Datwani","sequence":"first","affiliation":[{"name":"Faculty of Health Sciences, Simon Fraser University, Burnaby, BC V6A 1S6, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca","family":"Kalikawe","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, Simon Fraser University, Burnaby, BC V6A 1S6, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel","family":"Waterworth","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, Simon Fraser University, Burnaby, BC V6A 1S6, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francis M.","family":"Mwimanzi","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, Simon Fraser University, Burnaby, BC V6A 1S6, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Liang","sequence":"additional","affiliation":[{"name":"British Columbia Centre for Excellence in HIV\/AIDS, Vancouver, BC V6Z 1Y6, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yurou","family":"Sang","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, Simon Fraser University, Burnaby, BC V6A 1S6, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hope R.","family":"Lapointe","sequence":"additional","affiliation":[{"name":"British Columbia Centre for Excellence in HIV\/AIDS, Vancouver, BC V6Z 1Y6, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter K.","family":"Cheung","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, Simon Fraser University, Burnaby, BC V6A 1S6, Canada"},{"name":"British Columbia Centre for Excellence in HIV\/AIDS, Vancouver, BC V6Z 1Y6, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fredrick Harrison","family":"Omondi","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, Simon Fraser University, Burnaby, BC V6A 1S6, Canada"},{"name":"British Columbia Centre for Excellence in HIV\/AIDS, Vancouver, BC V6Z 1Y6, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maggie C.","family":"Duncan","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, Simon Fraser University, Burnaby, BC V6A 1S6, Canada"},{"name":"British Columbia Centre for Excellence in HIV\/AIDS, Vancouver, BC V6Z 1Y6, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evan","family":"Barad","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, Simon Fraser University, Burnaby, BC V6A 1S6, Canada"},{"name":"British Columbia Centre for Excellence in HIV\/AIDS, Vancouver, BC V6Z 1Y6, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Speckmaier","sequence":"additional","affiliation":[{"name":"British Columbia Centre for Excellence in HIV\/AIDS, Vancouver, BC V6Z 1Y6, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadia","family":"Moran-Garcia","sequence":"additional","affiliation":[{"name":"British Columbia Centre for Excellence in HIV\/AIDS, Vancouver, BC V6Z 1Y6, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9281-9547","authenticated-orcid":false,"given":"Mari L.","family":"DeMarco","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Providence Health Care, Vancouver, BC V6Z 1Y6, Canada"},{"name":"Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 1Z4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Malcolm","family":"Hedgcock","sequence":"additional","affiliation":[{"name":"Spectrum Health, Vancouver, BC V6Z 2T1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4547-714X","authenticated-orcid":false,"given":"Cecilia T.","family":"Costiniuk","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases Chronic Viral Illness Service, McGill University Health Centre, Montreal, QC H4A 3J1, Canada"},{"name":"Research Institute of the McGill University Health Centre, Montreal, QC H4A 3J1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Hull","sequence":"additional","affiliation":[{"name":"British Columbia Centre for Excellence in HIV\/AIDS, Vancouver, BC V6Z 1Y6, Canada"},{"name":"Department of Medicine, University of British Columbia, Vancouver, BC V6T 1Z4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marianne","family":"Harris","sequence":"additional","affiliation":[{"name":"British Columbia Centre for Excellence in HIV\/AIDS, Vancouver, BC V6Z 1Y6, Canada"},{"name":"Department of Family Practice, Faculty of Medicine, University of British Columbia, Vancouver, BC V6T 1Z4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc G.","family":"Romney","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Providence Health Care, Vancouver, BC V6Z 1Y6, Canada"},{"name":"Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 1Z4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julio S. G.","family":"Montaner","sequence":"additional","affiliation":[{"name":"British Columbia Centre for Excellence in HIV\/AIDS, Vancouver, BC V6Z 1Y6, Canada"},{"name":"Department of Medicine, University of British Columbia, Vancouver, BC V6T 1Z4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8157-1037","authenticated-orcid":false,"given":"Zabrina L.","family":"Brumme","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, Simon Fraser University, Burnaby, BC V6A 1S6, Canada"},{"name":"British Columbia Centre for Excellence in HIV\/AIDS, Vancouver, BC V6Z 1Y6, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6432-1426","authenticated-orcid":false,"given":"Mark A.","family":"Brockman","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, Simon Fraser University, Burnaby, BC V6A 1S6, Canada"},{"name":"British Columbia Centre for Excellence in HIV\/AIDS, Vancouver, BC V6Z 1Y6, Canada"},{"name":"Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC V6A 1S6, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,24]]},"reference":[{"key":"ref_1","unstructured":"Western Cape Department of Health in collaboration with the National Institute for Communicable Diseases, South Africa (2021). 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