Impact of antiretroviral therapy during acute or early HIV infection on virologic and immunologic outcomes : results from a multinational clinical trial
Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved..
OBJECTIVE: To assess how antiretroviral therapy (ART) initiation during acute or early HIV infection (AEHI) affects the viral reservoir and host immune responses.
DESIGN: Single-arm trial of ART initiation during AEHI at 30 sites in the Americas, Africa, and Asia.
METHODS: HIV DNA was measured at week 48 of ART in 5 million CD4+ T cells by sensitive qPCR assays targeting HIV gag and pol. Peripheral blood mononuclear cells were stimulated with potential HIV T cell epitope peptide pools consisting of env, gag, nef, and pol peptides and stained for expression of CD3, CD4, CD8, and intracellular cytokines/chemokines.
RESULTS: From 2017 to 2019, 188 participants initiated ART during Fiebig stages I (n = 6), II (n = 43), III (n = 56), IV (n = 23), and V (n = 60). Median age was 27 years (interquartile range 23-38), 27 (14%) participants were female, and 180 (97%) cisgender. Among 154 virally suppressed participants at week 48, 100% had detectable HIV gag or pol DNA. Participants treated during Fiebig I had the lowest HIV DNA levels (P < 0.001). Week 48 HIV DNA mostly did not correlate with concurrent CD4+ or CD8+ T cell HIV-specific immune responses (rho range -0.11 to +0.19, all P > 0.025). At week 48, the magnitude, but not polyfunctionality, of HIV-specific T cell responses was moderately reduced among participants who initiated ART earliest.
CONCLUSION: Earlier ART initiation during AEHI reduced but did not eliminate the persistence of HIV-infected cells in blood. These findings explain the rapid viral rebound observed after ART cessation in early-treated individuals with undetectable HIV DNA by less sensitive methods.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
AIDS (London, England) - (2024) vom: 14. März |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Crowell, Trevor A [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Revised 19.03.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1097/QAD.0000000000003881 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM369792572 |
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| 245 | 1 | 0 | |a Impact of antiretroviral therapy during acute or early HIV infection on virologic and immunologic outcomes |b results from a multinational clinical trial |
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| 500 | |a published: Print-Electronic | ||
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| 520 | |a Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved. | ||
| 520 | |a OBJECTIVE: To assess how antiretroviral therapy (ART) initiation during acute or early HIV infection (AEHI) affects the viral reservoir and host immune responses | ||
| 520 | |a DESIGN: Single-arm trial of ART initiation during AEHI at 30 sites in the Americas, Africa, and Asia | ||
| 520 | |a METHODS: HIV DNA was measured at week 48 of ART in 5 million CD4+ T cells by sensitive qPCR assays targeting HIV gag and pol. Peripheral blood mononuclear cells were stimulated with potential HIV T cell epitope peptide pools consisting of env, gag, nef, and pol peptides and stained for expression of CD3, CD4, CD8, and intracellular cytokines/chemokines | ||
| 520 | |a RESULTS: From 2017 to 2019, 188 participants initiated ART during Fiebig stages I (n = 6), II (n = 43), III (n = 56), IV (n = 23), and V (n = 60). Median age was 27 years (interquartile range 23-38), 27 (14%) participants were female, and 180 (97%) cisgender. Among 154 virally suppressed participants at week 48, 100% had detectable HIV gag or pol DNA. Participants treated during Fiebig I had the lowest HIV DNA levels (P < 0.001). Week 48 HIV DNA mostly did not correlate with concurrent CD4+ or CD8+ T cell HIV-specific immune responses (rho range -0.11 to +0.19, all P > 0.025). At week 48, the magnitude, but not polyfunctionality, of HIV-specific T cell responses was moderately reduced among participants who initiated ART earliest | ||
| 520 | |a CONCLUSION: Earlier ART initiation during AEHI reduced but did not eliminate the persistence of HIV-infected cells in blood. These findings explain the rapid viral rebound observed after ART cessation in early-treated individuals with undetectable HIV DNA by less sensitive methods | ||
| 650 | 4 | |a Journal Article | |
| 700 | 1 | |a Ritz, Justin |e verfasserin |4 aut | |
| 700 | 1 | |a Zheng, Lu |e verfasserin |4 aut | |
| 700 | 1 | |a Naqvi, Asma |e verfasserin |4 aut | |
| 700 | 1 | |a Cyktor, Joshua C |e verfasserin |4 aut | |
| 700 | 1 | |a Puleo, Joseph |e verfasserin |4 aut | |
| 700 | 1 | |a Clagett, Brian |e verfasserin |4 aut | |
| 700 | 1 | |a Lama, Javier R |e verfasserin |4 aut | |
| 700 | 1 | |a Kanyama, Cecilia |e verfasserin |4 aut | |
| 700 | 1 | |a Little, Susan J |e verfasserin |4 aut | |
| 700 | 1 | |a Cohn, Susan E |e verfasserin |4 aut | |
| 700 | 1 | |a Riddler, Sharon A |e verfasserin |4 aut | |
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