HIV viral set point and host immune control in individuals with HIV-specific CD8+ T-cell responses prior to HIV acquisition.
OBJECTIVE: Vaccine-induced CD8(+) T-cell responses in primates have been associated with a reduced simian immunodeficiency virus plasma viral load and enhanced T-cell responses, but cellular vaccines have shown limited success in human trials. We previously described HIV-specific T-cell responses in...
المؤلفون الرئيسيون: | , , , , , , , , , , , |
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التنسيق: | Journal article |
اللغة: | English |
منشور في: |
2010
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_version_ | 1826257910531883008 |
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author | Kaul, R MacDonald, K Nagelkerke, N Kimani, J Fowke, K Ball, T Luo, M Kariri, A Jaoko, W Moses, S Rowland-Jones, S Plummer, F |
author_facet | Kaul, R MacDonald, K Nagelkerke, N Kimani, J Fowke, K Ball, T Luo, M Kariri, A Jaoko, W Moses, S Rowland-Jones, S Plummer, F |
author_sort | Kaul, R |
collection | OXFORD |
description | OBJECTIVE: Vaccine-induced CD8(+) T-cell responses in primates have been associated with a reduced simian immunodeficiency virus plasma viral load and enhanced T-cell responses, but cellular vaccines have shown limited success in human trials. We previously described HIV-specific T-cell responses in two groups of highly exposed, persistently seronegative Kenyan female sex workers, and a subset of these participants have subsequently acquired HIV. We examined the impact of pre-existing CD8(+) T-cell responses on post-acquisition outcomes. DESIGN AND METHODS: HIV-specific CD8(+) T-cell responses had been examined in highly exposed, persistently seronegative participants from the Pumwani and Kibera cohorts, using a combination of virus-specific lysis, proliferation, interferon-gamma production, or all. Plasma viral load set point and HIV-specific T-cell proliferation and cytokine production were now examined post hoc by blinded investigators in the subset of participants who acquired HIV. RESULTS: Pre-acquisition cellular immune assays and post-infection viral load were available for 46 participants, and HIV-specific CD8(+) T-cell responses had been detected in 25 of 46 (54%) participants. Pre-acquisition CD8(+) T-cell responses were associated with a lower post-acquisition HIV viral load set point in both cohorts (pooled analysis, 3.1 vs. 4.1 log(10) RNA copies/ml; P=0.0002) and with enhanced post-acquisition HIV-specific CD8(+) T-cell proliferation (3.8 vs. 1.0%, P=0.03), but with a trend to reduced post-acquisition CD8(+) T-cell interferon-gamma responses. CONCLUSION: HIV-specific CD8(+) T-cell responses prior to HIV acquisition were associated with a lower HIV viral load and an altered functional profile of post-acquisition CD8(+) T-cell responses. |
first_indexed | 2024-03-06T18:25:39Z |
format | Journal article |
id | oxford-uuid:07dc967c-a971-4f3d-9da4-d60eabcd7a19 |
institution | University of Oxford |
language | English |
last_indexed | 2024-03-06T18:25:39Z |
publishDate | 2010 |
record_format | dspace |
spelling | oxford-uuid:07dc967c-a971-4f3d-9da4-d60eabcd7a192022-03-26T09:09:50ZHIV viral set point and host immune control in individuals with HIV-specific CD8+ T-cell responses prior to HIV acquisition.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:07dc967c-a971-4f3d-9da4-d60eabcd7a19EnglishSymplectic Elements at Oxford2010Kaul, RMacDonald, KNagelkerke, NKimani, JFowke, KBall, TLuo, MKariri, AJaoko, WMoses, SRowland-Jones, SPlummer, FOBJECTIVE: Vaccine-induced CD8(+) T-cell responses in primates have been associated with a reduced simian immunodeficiency virus plasma viral load and enhanced T-cell responses, but cellular vaccines have shown limited success in human trials. We previously described HIV-specific T-cell responses in two groups of highly exposed, persistently seronegative Kenyan female sex workers, and a subset of these participants have subsequently acquired HIV. We examined the impact of pre-existing CD8(+) T-cell responses on post-acquisition outcomes. DESIGN AND METHODS: HIV-specific CD8(+) T-cell responses had been examined in highly exposed, persistently seronegative participants from the Pumwani and Kibera cohorts, using a combination of virus-specific lysis, proliferation, interferon-gamma production, or all. Plasma viral load set point and HIV-specific T-cell proliferation and cytokine production were now examined post hoc by blinded investigators in the subset of participants who acquired HIV. RESULTS: Pre-acquisition cellular immune assays and post-infection viral load were available for 46 participants, and HIV-specific CD8(+) T-cell responses had been detected in 25 of 46 (54%) participants. Pre-acquisition CD8(+) T-cell responses were associated with a lower post-acquisition HIV viral load set point in both cohorts (pooled analysis, 3.1 vs. 4.1 log(10) RNA copies/ml; P=0.0002) and with enhanced post-acquisition HIV-specific CD8(+) T-cell proliferation (3.8 vs. 1.0%, P=0.03), but with a trend to reduced post-acquisition CD8(+) T-cell interferon-gamma responses. CONCLUSION: HIV-specific CD8(+) T-cell responses prior to HIV acquisition were associated with a lower HIV viral load and an altered functional profile of post-acquisition CD8(+) T-cell responses. |
spellingShingle | Kaul, R MacDonald, K Nagelkerke, N Kimani, J Fowke, K Ball, T Luo, M Kariri, A Jaoko, W Moses, S Rowland-Jones, S Plummer, F HIV viral set point and host immune control in individuals with HIV-specific CD8+ T-cell responses prior to HIV acquisition. |
title | HIV viral set point and host immune control in individuals with HIV-specific CD8+ T-cell responses prior to HIV acquisition. |
title_full | HIV viral set point and host immune control in individuals with HIV-specific CD8+ T-cell responses prior to HIV acquisition. |
title_fullStr | HIV viral set point and host immune control in individuals with HIV-specific CD8+ T-cell responses prior to HIV acquisition. |
title_full_unstemmed | HIV viral set point and host immune control in individuals with HIV-specific CD8+ T-cell responses prior to HIV acquisition. |
title_short | HIV viral set point and host immune control in individuals with HIV-specific CD8+ T-cell responses prior to HIV acquisition. |
title_sort | hiv viral set point and host immune control in individuals with hiv specific cd8 t cell responses prior to hiv acquisition |
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