11 results on '"Moran-Garcia N"'
Search Results
2. Effects of COVID-19 mRNA vaccination on HIV viremia and reservoir size.
- Author
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Duncan MC, Omondi FH, Kinloch NN, Lapointe HR, Speckmaier S, Moran-Garcia N, Lawson T, DeMarco ML, Simons J, Holmes DT, Lowe CF, Bacani N, Sereda P, Barrios R, Harris M, Romney MG, Montaner JSG, Brumme CJ, Brockman MA, and Brumme ZL
- Subjects
- Humans, Male, Female, Middle Aged, Adult, Longitudinal Studies, Antibodies, Viral blood, British Columbia, Vaccination, Disease Reservoirs virology, HIV Infections drug therapy, HIV Infections prevention & control, Viral Load, COVID-19 Vaccines immunology, COVID-19 Vaccines administration & dosage, COVID-19 prevention & control, Viremia, SARS-CoV-2 immunology
- Abstract
Objective: The immunogenic nature of coronavirus disease 2019 (COVID-19) mRNA vaccines led to some initial concern that these could stimulate the HIV reservoir. We analyzed changes in plasma HIV loads (pVL) and reservoir size following COVID-19 mRNA vaccination in 62 people with HIV (PWH) receiving antiretroviral therapy (ART), and analyzed province-wide trends in pVL before and after the mass vaccination campaign., Design: Longitudinal observational cohort and province-wide analysis., Methods: Sixty-two participants were sampled prevaccination, and one month after their first and second COVID-19 immunizations. Vaccine-induced anti-SARS-CoV-2-Spike antibodies in serum were measured using the Roche Elecsys Anti-S assay. HIV reservoirs were quantified using the intact proviral DNA assay; pVL were measured using the cobas 6800 (lower limit of quantification: 20 copies/ml). The province-wide analysis included all 290 401 pVL performed in British Columbia, Canada between 2012 and 2022., Results: Prevaccination, the median intact reservoir size was 77 [interquartile range (IQR): 20-204] HIV copies/million CD4 + T-cells, compared to 74 (IQR: 27-212) and 65 (IQR: 22-174) postfirst and -second dose, respectively (all comparisons P > 0.07). Prevaccination, 82% of participants had pVL <20 copies/ml (max: 110 copies/ml), compared to 79% postfirst dose (max: 183 copies/ml) and 85% postsecond dose (max: 79 copies/ml) ( P > 0.4). There was no evidence that the magnitude of the vaccine-elicited anti-SARS-CoV-2-Spike immune response influenced pVL nor changes in reservoir size ( P > 0.6). We found no evidence linking the COVID-19 mass vaccination campaign to population-level increases in detectable pVL frequency among all PWH in the province, nor among those who maintained pVL suppression on ART., Conclusion: We found no evidence that COVID-19 mRNA vaccines induced changes in HIV reservoir size nor plasma viremia., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)
- Published
- 2024
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3. T-Cell Responses to COVID-19 Vaccines and Breakthrough Infection in People Living with HIV Receiving Antiretroviral Therapy.
- Author
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Datwani S, Kalikawe R, Waterworth R, Mwimanzi FM, Liang R, Sang Y, Lapointe HR, Cheung PK, Omondi FH, Duncan MC, Barad E, Speckmaier S, Moran-Garcia N, DeMarco ML, Hedgcock M, Costiniuk CT, Hull M, Harris M, Romney MG, Montaner JSG, Brumme ZL, and Brockman MA
- Subjects
- Humans, Male, Female, Middle Aged, Adult, Spike Glycoprotein, Coronavirus immunology, Antibodies, Viral blood, Antibodies, Viral immunology, Aged, Immunity, Cellular, Breakthrough Infections, HIV Infections immunology, HIV Infections drug therapy, COVID-19 Vaccines immunology, COVID-19 Vaccines administration & dosage, SARS-CoV-2 immunology, COVID-19 immunology, COVID-19 prevention & control, CD8-Positive T-Lymphocytes immunology, CD4-Positive T-Lymphocytes immunology
- Abstract
People living with HIV (PLWH) can exhibit impaired immune responses to vaccines. 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 < 0.0001). Median T-cell frequencies did not differ between PLWH and controls after the second dose ( p > 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 < 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.
- Published
- 2024
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4. Effects of COVID-19 mRNA vaccination on HIV viremia and reservoir size.
- Author
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Duncan MC, Omondi FH, Kinloch NN, Lapointe HR, Speckmaier S, Moran-Garcia N, Lawson T, DeMarco ML, Simons J, Holmes DT, Lowe CF, Bacani N, Sereda P, Barrios R, Harris M, Romney MG, Montaner JSG, Brumme CJ, Brockman MA, and Brumme ZL
- Abstract
Objective: The immunogenic nature of COVID-19 mRNA vaccines led to some initial concern that these could stimulate the HIV reservoir. We analyzed changes in plasma HIV loads (pVL) and reservoir size following COVID-19 mRNA vaccination in 62 people with HIV (PWH) receiving antiretroviral therapy (ART), and analyzed province-wide trends in pVL before and after the mass vaccination campaign., Design: Longitudinal observational cohort and province-wide analysis., Methods: 62 participants were sampled pre-vaccination, and one month after their first and second COVID-19 immunizations. Vaccine-induced anti-SARS-CoV-2-Spike antibodies in serum were measured using the Roche Elecsys Anti-S assay. HIV reservoirs were quantified using the Intact Proviral DNA Assay; pVL were measured using the cobas 6800 (LLOQ:20 copies/mL). The province-wide analysis included all 290,401 pVL performed in British Columbia, Canada between 2012-2022., Results: Pre-vaccination, the median intact reservoir size was 77 (IQR:20-204) HIV copies/million CD4+ T-cells, compared to 74 (IQR:27-212) and 65 (IQR:22-174) post-first and -second dose, respectively (all comparisons p>0.07). Pre-vaccination, 82% of participants had pVL<20 copies/mL (max:110 copies/mL), compared to 79% post-first dose (max:183 copies/mL) and 85% post-second dose (max:79 copies/mL) (p>0.4). The magnitude of the vaccine-elicited anti-SARS-CoV-2-Spike antibody response did not correlate with changes in reservoir size nor detectable pVL frequency (p>0.6). We found no evidence linking the COVID-19 mass vaccination campaign to population-level increases in detectable pVL frequency among all PWH in the province, nor among those who maintained pVL suppression on ART., Conclusion: We found no evidence that COVID-19 mRNA vaccines induced changes in HIV reservoir size nor plasma viremia.
- Published
- 2023
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5. People With Human Immunodeficiency Virus Receiving Suppressive Antiretroviral Therapy Show Typical Antibody Durability After Dual Coronavirus Disease 2019 Vaccination and Strong Third Dose Responses.
- Author
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Lapointe HR, Mwimanzi F, Cheung PK, Sang Y, Yaseen F, Umviligihozo G, Kalikawe R, Speckmaier S, Moran-Garcia N, Datwani S, Duncan MC, Agafitei O, Ennis S, Young L, Ali H, Ganase B, Omondi FH, Dong W, Toy J, Sereda P, Burns L, Costiniuk CT, Cooper C, Anis AH, Leung V, Holmes DT, DeMarco ML, Simons J, Hedgcock M, Prystajecky N, Lowe CF, Pantophlet R, Romney MG, Barrios R, Guillemi S, Brumme CJ, Montaner JSG, Hull M, Harris M, Niikura M, Brockman MA, and Brumme ZL
- Subjects
- Humans, HIV, COVID-19 Vaccines, SARS-CoV-2, Antibodies, Vaccination, Antibodies, Viral, COVID-19 prevention & control, HIV Infections drug therapy
- Abstract
Background: Longer-term humoral responses to 2-dose coronavirus disease 2019 (COVID-19) vaccines remain incompletely characterized in people living with human immunodeficiency virus (HIV) (PLWH), as do initial responses to a third dose., Methods: We measured antibodies against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein receptor-binding domain, angiotensin-converting enzyme 2 (ACE2) displacement, and viral neutralization against wild-type and Omicron strains up to 6 months after 2-dose vaccination, and 1 month after the third dose, in 99 PLWH receiving suppressive antiretroviral therapy and 152 controls., Results: Although humoral responses naturally decline after 2-dose vaccination, we found no evidence of lower antibody concentrations or faster rates of antibody decline in PLWH compared with controls after accounting for sociodemographic, health, and vaccine-related factors. We also found no evidence of poorer viral neutralization in PLWH after 2 doses, nor evidence that a low nadir CD4+ T-cell count compromised responses. Post-third-dose humoral responses substantially exceeded post-second-dose levels, though Omicron-specific responses were consistently weaker than responses against wild-type virus. Nevertheless, post-third-dose responses in PLWH were comparable to or higher than controls. An mRNA-1273 third dose was the strongest consistent correlate of higher post-third-dose responses., Conclusion: PLWH receiving suppressive antiretroviral therapy mount strong antibody responses after 2- and 3-dose COVID-19 vaccination. Results underscore the immune benefits of third doses in light of Omicron., Competing Interests: Potential conflicts of interest. All authors: no reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
- Published
- 2023
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6. Antibody response durability following three-dose coronavirus disease 2019 vaccination in people with HIV receiving suppressive antiretroviral therapy.
- Author
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Lapointe HR, Mwimanzi F, Cheung PK, Sang Y, Yaseen F, Speckmaier S, Barad E, Moran-Garcia N, Datwani S, Duncan MC, Kalikawe R, Ennis S, Young L, Ganase B, Omondi FH, Umviligihozo G, Dong W, Toy J, Sereda P, Burns L, Costiniuk CT, Cooper C, Anis AH, Leung V, Holmes D, DeMarco ML, Simons J, Hedgcock M, Prystajecky N, Lowe CF, Romney MG, Barrios R, Guillemi S, Brumme CJ, Montaner JSG, Hull M, Harris M, Niikura M, Brockman MA, and Brumme ZL
- Subjects
- Humans, Antibody Formation, COVID-19 Vaccines, SARS-CoV-2, Vaccination, Immunoglobulin G, Antibodies, Viral, Antibodies, Neutralizing, COVID-19 prevention & control, HIV Infections complications, HIV Infections drug therapy
- Abstract
Background: Limited data exist regarding longer term antibody responses following three-dose coronavirus disease 2019 (COVID-19) vaccination, and the impact of a first SARS-CoV-2 infection during this time, in people with HIV (PWH) receiving suppressive antiretroviral therapy (ART). We quantified wild-type-specific, Omicron BA.1-specific and Omicron BA.5-specific responses up to 6 months post-third dose in 64 PWH and 117 controls who remained COVID-19-naive or experienced their first SARS-CoV-2 infection during this time., Design: Longitudinal observational cohort., Methods: We quantified wild-type-specific and Omicron-specific anti-Spike receptor-binding domain IgG concentrations, ACE2 displacement activities and live virus neutralization at 1, 3 and 6 months post-third vaccine dose., Results: Third doses boosted all antibody measures above two-dose levels, but BA.1-specific responses remained significantly lower than wild-type-specific ones, with BA.5-specific responses lower still. Serum IgG concentrations declined at similar rates in COVID-19-naive PWH and controls post-third dose (median wild-type-specific and BA.1-specific half-lives were between 66 and 74 days for both groups). Antibody function also declined significantly yet comparably between groups: 6 months post-third dose, BA.1-specific neutralization was undetectable in more than 80% of COVID-19 naive PWH and more than 90% of controls. Breakthrough SARS-CoV-2 infection boosted antibody concentrations and function significantly above vaccine-induced levels in both PWH and controls, though BA.5-specific neutralization remained significantly poorer than BA.1 even post-breakthrough., Conclusion: Following three-dose COVID-19 vaccination, antibody response durability in PWH receiving ART is comparable with controls. PWH also mounted strong responses to breakthrough infection. Due to temporal response declines, however, COVID-19-naive individuals, regardless of HIV status, would benefit from a fourth dose within 6 months of their third., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)
- Published
- 2023
- Full Text
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7. SARS CoV-2 mRNA vaccination exposes latent HIV to Nef-specific CD8 + T-cells.
- Author
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Stevenson EM, Terry S, Copertino D, Leyre L, Danesh A, Weiler J, Ward AR, Khadka P, McNeil E, Bernard K, Miller IG, Ellsworth GB, Johnston CD, Finkelsztein EJ, Zumbo P, Betel D, Dündar F, Duncan MC, Lapointe HR, Speckmaier S, Moran-Garcia N, Papa MP, Nicholes S, Stover CJ, Lynch RM, Caskey M, Gaebler C, Chun TW, Bosque A, Wilkin TJ, Lee GQ, Brumme ZL, and Jones RB
- Subjects
- BNT162 Vaccine, CD4-Positive T-Lymphocytes, Granzymes, Humans, RNA, Messenger genetics, RNA, Messenger therapeutic use, SARS-CoV-2, Vaccination, Vaccines, Synthetic, Virus Latency, mRNA Vaccines, nef Gene Products, Human Immunodeficiency Virus genetics, CD8-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes virology, COVID-19 prevention & control, COVID-19 Vaccines immunology, HIV Infections immunology, HIV-1
- Abstract
Efforts to cure HIV have focused on reactivating latent proviruses to enable elimination by CD8
+ cytotoxic T-cells. Clinical studies of latency reversing agents (LRA) in antiretroviral therapy (ART)-treated individuals have shown increases in HIV transcription, but without reductions in virologic measures, or evidence that HIV-specific CD8+ T-cells were productively engaged. Here, we show that the SARS-CoV-2 mRNA vaccine BNT162b2 activates the RIG-I/TLR - TNF - NFκb axis, resulting in transcription of HIV proviruses with minimal perturbations of T-cell activation and host transcription. T-cells specific for the early gene-product HIV-Nef uniquely increased in frequency and acquired effector function (granzyme-B) in ART-treated individuals following SARS-CoV-2 mRNA vaccination. These parameters of CD8+ T-cell induction correlated with significant decreases in cell-associated HIV mRNA, suggesting killing or suppression of cells transcribing HIV. Thus, we report the observation of an intervention-induced reduction in a measure of HIV persistence, accompanied by precise immune correlates, in ART-suppressed individuals. However, we did not observe significant depletions of intact proviruses, underscoring challenges to achieving (or measuring) HIV reservoir reductions. Overall, our results support prioritizing the measurement of granzyme-B-producing Nef-specific responses in latency reversal studies and add impetus to developing HIV-targeted mRNA therapeutic vaccines that leverage built-in LRA activity., (© 2022. The Author(s).)- Published
- 2022
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8. A Novel Adult Murine Model of Typical Enteroaggregative Escherichia coli Infection Reveals Microbiota Dysbiosis, Mucus Secretion, and AAF/II-Mediated Expression and Localization of β-Catenin and Expression of MUC1 in Ileum.
- Author
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Moran-Garcia N, Lopez-Saucedo C, Becerra A, Meza-Segura M, Hernandez-Cazares F, Guerrero-Baez J, Galindo-Gómez S, Tsutsumi V, Schnoor M, Méndez-Tenorio A, Nataro JP, and Estrada-Garcia T
- Subjects
- Adhesins, Escherichia coli genetics, Animals, Bacterial Adhesion genetics, Diarrhea microbiology, Disease Models, Animal, Dysbiosis, Escherichia coli genetics, Escherichia coli metabolism, Humans, Mice, Mice, Inbred C57BL, Mucus metabolism, Travel, Escherichia coli Infections microbiology, Ileum, Microbiota, Mucin-1 genetics, beta Catenin genetics
- Abstract
Typical enteroaggregative Escherichia coli (tEAEC) is a diarrheagenic E. coli pathotype associated with pediatric and traveler's diarrhea. Even without diarrhea, EAEC infections in children also lead to increased gut inflammation and growth shortfalls. EAEC strain's defining phenotype is the aggregative adherence pattern on epithelial cells attributable to the aggregative adherence fimbriae (AAF). EAEC only causes diarrhea in humans; therefore, not much is known of the exact intestinal region of infection and damage or its interactions with intestinal enterocytes in vivo and in situ . This study aimed to develop a new tEAEC mouse model of infection, characterize the microbiota of infected mice, and evaluate in situ the expression of host adherence and surface molecules triggering EAEC infection and the role of the EAEC AAF-II in adherence. Six-week-old C57BL/6 mice, without previous antibiotic treatment, were orally challenged with EAEC 042 strain or EAEC 042 AAF-II mutant (ΔAAF/II) strain, or DAEC-MXR strain (diffusely adherent E. coli clinical isolate), and with saline solution (control group). Paraffin sections of the colon and ileum were stained with H&E and periodic acid-Schiff. ZO-1, β-catenin, MUC1, and bacteria were analyzed by immunofluorescence. EAEC-infected mice, in comparison with DAEC-MXR-infected and control mice, significantly lost weight during the first 3 days. After 7 days post-infection, mucus production was increased in the colon and ileum, ZO-1 localization remained unaltered, and morphological alterations were more pronounced in the ileum since increased expression and apical localization of β-catenin in ileal enterocytes were observed. EAEC-infected mice developed dysbiosis 21 days post-infection. At 4 days post-infection, EAEC strain 042 formed a biofilm on ileal villi and increased the expression and apical localization of β-catenin in ileal enterocytes; these effects were not seen in animals infected with the 042 ΔAAF/II strain. At 3 days post-infection, MUC1 expression on ileal enterocytes was mainly detectable among infected mice and colocalized with 042 strains on the enterocyte surface. We developed a novel mouse model of EAEC infection, which mimics human infection, not an illness, revealing that EAEC 042 exerts its pathogenic effects in the mouse ileum and causes dysbiosis. This model is a unique tool to unveil early molecular mechanisms of EAEC infection in vivo and in situ ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Moran-Garcia, Lopez-Saucedo, Becerra, Meza-Segura, Hernandez-Cazares, Guerrero-Baez, Galindo-Gómez, Tsutsumi, Schnoor, Méndez-Tenorio, Nataro and Estrada-Garcia.)
- Published
- 2022
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9. People with HIV receiving suppressive antiretroviral therapy show typical antibody durability after dual COVID-19 vaccination, and strong third dose responses.
- Author
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Lapointe HR, Mwimanzi F, Cheung PK, Sang Y, Yaseen F, Umviligihozo G, Kalikawe R, Speckmaier S, Moran-Garcia N, Datwani S, Duncan MC, Agafitei O, Ennis S, Young L, Ali H, Ganase B, Omondi FH, Dong W, Toy J, Sereda P, Burns L, Costiniuk CT, Cooper C, Anis AH, Leung V, Holmes D, DeMarco ML, Simons J, Hedgcock M, Prystajecky N, Lowe CF, Pantophlet R, Romney MG, Barrios R, Guillemi S, Brumme CJ, Montaner JSG, Hull M, Harris M, Niikura M, Brockman MA, and Brumme ZL
- Abstract
Background: Longer-term humoral responses to two-dose COVID-19 vaccines remain incompletely characterized in people living with HIV (PLWH), as do initial responses to a third dose., Methods: We measured antibodies against the SARS-CoV-2 spike protein receptor-binding domain, ACE2 displacement and viral neutralization against wild-type and Omicron strains up to six months following two-dose vaccination, and one month following the third dose, in 99 PLWH receiving suppressive antiretroviral therapy, and 152 controls., Results: Though humoral responses naturally decline following two-dose vaccination, we found no evidence of lower antibody concentrations nor faster rates of antibody decline in PLWH compared to controls after accounting for sociodemographic, health and vaccine-related factors. We also found no evidence of poorer viral neutralization in PLWH after two doses, nor evidence that a low nadir CD4+ T-cell count compromised responses. Post-third-dose humoral responses substantially exceeded post-second-dose levels, though anti-Omicron responses were consistently weaker than against wild-type.Nevertheless, post-third-dose responses in PLWH were comparable to or higher than controls. An mRNA-1273 third dose was the strongest consistent correlate of higher post-third-dose responses., Conclusion: PLWH receiving suppressive antiretroviral therapy mount strong antibody responses after two- and three-dose COVID-19 vaccination. Results underscore the immune benefits of third doses in light of Omicron.
- Published
- 2022
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- View/download PDF
10. Humoral immune responses to COVID-19 vaccination in people living with HIV receiving suppressive antiretroviral therapy.
- Author
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Brumme ZL, Mwimanzi F, Lapointe HR, Cheung PK, Sang Y, Duncan MC, Yaseen F, Agafitei O, Ennis S, Ng K, Basra S, Lim LY, Kalikawe R, Speckmaier S, Moran-Garcia N, Young L, Ali H, Ganase B, Umviligihozo G, Omondi FH, Atkinson K, Sudderuddin H, Toy J, Sereda P, Burns L, Costiniuk CT, Cooper C, Anis AH, Leung V, Holmes D, DeMarco ML, Simons J, Hedgcock M, Romney MG, Barrios R, Guillemi S, Brumme CJ, Pantophlet R, Montaner JSG, Niikura M, Harris M, Hull M, and Brockman MA
- Abstract
Humoral responses to COVID-19 vaccines in people living with HIV (PLWH) remain incompletely characterized. We measured circulating antibodies against the SARS-CoV-2 spike protein receptor-binding domain (RBD), ACE2 displacement and viral neutralization activities one month following the first and second COVID-19 vaccine doses, and again 3 months following the second dose, in 100 adult PLWH and 152 controls. All PLWH were receiving suppressive antiretroviral therapy, with median CD4+ T-cell counts of 710 (IQR 525-935) cells/mm
3 , though nadir CD4+ T-cell counts ranged as low as <10 cells/mm3 . After adjustment for sociodemographic, health and vaccine-related variables, HIV infection was associated with lower anti-RBD antibody concentrations and ACE2 displacement activity after one vaccine dose. Following two doses however, HIV was not significantly associated with the magnitude of any humoral response after multivariable adjustment. Rather, older age, a higher burden of chronic health conditions, and dual ChAdOx1 vaccination were associated with lower responses after two vaccine doses. No significant correlation was observed between recent or nadir CD4+ T-cell counts and responses to two vaccine doses in PLWH. These results indicate that PLWH with well-controlled viral loads and CD4+ T-cell counts in a healthy range generally mount strong initial humoral responses to dual COVID-19 vaccination. Factors including age, co-morbidities, vaccine brand, response durability and the rise of new SARS-CoV-2 variants will influence when PLWH will benefit from additional doses. Further studies of PLWH who are not receiving antiretroviral treatment or who have low CD4+ T-cell counts are needed, as are longer-term assessments of response durability., (© 2022. The Author(s).)- Published
- 2022
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11. Humoral immune responses to COVID-19 vaccination in people living with HIV receiving suppressive antiretroviral therapy.
- Author
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Brumme ZL, Mwimanzi F, Lapointe HR, Cheung P, Sang Y, Duncan MC, Yaseen F, Agafitei O, Ennis S, Ng K, Basra S, Lim LY, Kalikawe R, Speckmaier S, Moran-Garcia N, Young L, Ali H, Ganase B, Umviligihozo G, Omondi FH, Atkinson K, Sudderuddin H, Toy J, Sereda P, Burns L, Costiniuk CT, Cooper C, Anis AH, Leung V, Holmes D, DeMarco ML, Simons J, Hedgcock M, Romney MG, Barrios R, Guillemi S, Brumme CJ, Pantophlet R, Montaner JSG, Niikura M, Harris M, Hull M, and Brockman MA
- Abstract
Humoral responses to COVID-19 vaccines in people living with HIV (PLWH) remain incompletely understood. We measured circulating antibodies against the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein, ACE2 displacement and live viral neutralization activities one month following the first and second COVID-19 vaccine doses in 100 adult PLWH and 152 controls. All PLWH were receiving suppressive antiretroviral therapy, with median CD4+ T-cell counts of 710 (IQR 525-935) cells/mm
3 . Nadir CD4+ T-cell counts ranged as low as <10 (median 280; IQR 120-490) cells/mm3 . After adjustment for sociodemographic, health and vaccine-related variables, HIV infection was significantly associated with 0.2 log10 lower anti-RBD antibody concentrations (p=0.03) and ∼11% lower ACE2 displacement activity (p=0.02), but not lower viral neutralization (p=0.1) after one vaccine dose. Following two doses however, HIV was no longer significantly associated with the magnitude of any response measured. Rather, older age, a higher burden of chronic health conditions, and having received two ChAdOx1 doses (versus a heterologous or dual mRNA vaccine regimen) were independently associated with lower responses. After two vaccine doses, no significant correlation was observed between the most recent or nadir CD4+ T-cell counts and vaccine responses in PLWH. These results suggest that PLWH with well-controlled viral loads on antiretroviral therapy and CD4+ T-cell counts in a healthy range will generally not require a third COVID-19 vaccine dose as part of their initial immunization series, though other factors such as older age, co-morbidities, vaccine regimen type, and durability of vaccine responses will influence when this group may benefit from additional doses. Further studies of PLWH who are not receiving antiretroviral treatment and/or who have low CD4+ T-cell counts are needed.- Published
- 2021
- Full Text
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