Long-term persistence of transcriptionally active 'defective' HIV-1 proviruses : implications for persistent immune activation during antiretroviral therapy
OBJECTIVES: People with HIV-1 (PWH) on effective antiretroviral therapy (ART) continue to exhibit chronic systemic inflammation, immune activation, and persistent elevations in markers of HIV-1 infection [including HIV-DNA, cell-associated HIV-RNA (CA HIV-RNA), and antibodies to HIV-1 proteins] despite prolonged suppression of plasma HIV-RNA levels less than 50 copies/ml. Here, we investigated the hypothesis that nonreplicating but transcriptionally and translationally competent 'defective' HIV-1 proviruses may be one of drivers of these phenomena.
DESIGN: A combined cohort of 23 viremic and virologically suppressed individuals on ART were studied.
METHODS: HIV-DNA, CA HIV-RNA, western blot score (measure of anti-HIV-1 antibodies as a surrogate for viral protein expression in vivo ), and key biomarkers of inflammation and coagulation (IL-6, hsCRP, TNF-alpha, tissue factor, and D-dimer) were measured in peripheral blood and analyzed using a combined cross-sectional and longitudinal approaches. Sequences of HIV-DNA and CA HIV-RNA obtained via 5'-LTR-to-3'-LTR PCR and single-genome sequencing were also analyzed.
RESULTS: We observed similar long-term persistence of multiple, unique, transcriptionally active 'defective' HIV-1 provirus clones (average: 11 years., range: 4-20 years) and antibody responses against HIV-1 viral proteins among all ART-treated participants evaluated. A direct correlation was observed between the magnitude of HIV-1 western blot score and the levels of transcription of 'defective' HIV-1 proviruses ( r = 0.73, P < 0.01). Additional correlations were noted between total CD8 + T-cell counts and HIV-DNA ( r = 0.52, P = 0.01) or CA HIV-RNA ( r = 0.65, P < 0.01).
CONCLUSION: These findings suggest a novel interplay between transcription and translation of 'defective' HIV-1 proviruses and the persistent immune activation seen in the setting of treated chronic HIV-1 infection.
| Errataetall: |
CommentIn: AIDS. 2023 Nov 15;37(14):2239-2241. - PMID 37877277 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:37 |
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| Enthalten in: |
AIDS (London, England) - 37(2023), 14 vom: 15. Nov., Seite 2119-2130 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Singh, Kanal [VerfasserIn] |
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| Links: |
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| Themen: |
DNA, Viral |
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| Anmerkungen: |
Date Completed 26.10.2023 Date Revised 04.11.2023 published: Print-Electronic CommentIn: AIDS. 2023 Nov 15;37(14):2239-2241. - PMID 37877277 Citation Status MEDLINE |
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| doi: |
10.1097/QAD.0000000000003667 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 500 | |a CommentIn: AIDS. 2023 Nov 15;37(14):2239-2241. - PMID 37877277 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a OBJECTIVES: People with HIV-1 (PWH) on effective antiretroviral therapy (ART) continue to exhibit chronic systemic inflammation, immune activation, and persistent elevations in markers of HIV-1 infection [including HIV-DNA, cell-associated HIV-RNA (CA HIV-RNA), and antibodies to HIV-1 proteins] despite prolonged suppression of plasma HIV-RNA levels less than 50 copies/ml. Here, we investigated the hypothesis that nonreplicating but transcriptionally and translationally competent 'defective' HIV-1 proviruses may be one of drivers of these phenomena | ||
| 520 | |a DESIGN: A combined cohort of 23 viremic and virologically suppressed individuals on ART were studied | ||
| 520 | |a METHODS: HIV-DNA, CA HIV-RNA, western blot score (measure of anti-HIV-1 antibodies as a surrogate for viral protein expression in vivo ), and key biomarkers of inflammation and coagulation (IL-6, hsCRP, TNF-alpha, tissue factor, and D-dimer) were measured in peripheral blood and analyzed using a combined cross-sectional and longitudinal approaches. Sequences of HIV-DNA and CA HIV-RNA obtained via 5'-LTR-to-3'-LTR PCR and single-genome sequencing were also analyzed | ||
| 520 | |a RESULTS: We observed similar long-term persistence of multiple, unique, transcriptionally active 'defective' HIV-1 provirus clones (average: 11 years., range: 4-20 years) and antibody responses against HIV-1 viral proteins among all ART-treated participants evaluated. A direct correlation was observed between the magnitude of HIV-1 western blot score and the levels of transcription of 'defective' HIV-1 proviruses ( r = 0.73, P < 0.01). Additional correlations were noted between total CD8 + T-cell counts and HIV-DNA ( r = 0.52, P = 0.01) or CA HIV-RNA ( r = 0.65, P < 0.01) | ||
| 520 | |a CONCLUSION: These findings suggest a novel interplay between transcription and translation of 'defective' HIV-1 proviruses and the persistent immune activation seen in the setting of treated chronic HIV-1 infection | ||
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| 700 | 1 | |a Badralmaa, Yuden |e verfasserin |4 aut | |
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