Impact of a TLR9 agonist and broadly neutralizing antibodies on HIV-1 persistence : the randomized phase 2a TITAN trial
© 2023. The Author(s)..
Inducing antiretroviral therapy (ART)-free virological control is a critical step toward a human immunodeficiency virus type 1 (HIV-1) cure. In this phase 2a, placebo-controlled, double-blinded trial, 43 people (85% males) with HIV-1 on ART were randomized to (1) placebo/placebo, (2) lefitolimod (TLR9 agonist)/placebo, (3) placebo/broadly neutralizing anti-HIV-1 antibodies (bNAbs) or (4) lefitolimod/bNAb. ART interruption (ATI) started at week 3. Lefitolimod was administered once weekly for the first 8 weeks, and bNAbs were administered twice, 1 d before and 3 weeks after ATI. The primary endpoint was time to loss of virologic control after ATI. The median delay in time to loss of virologic control compared to the placebo/placebo group was 0.5 weeks (P = 0.49), 12.5 weeks (P = 0.003) and 9.5 weeks (P = 0.004) in the lefitolimod/placebo, placebo/bNAb and lefitolimod/bNAb groups, respectively. Among secondary endpoints, viral doubling time was slower for bNAb groups compared to non-bNAb groups, and the interventions were overall safe. We observed no added benefit of lefitolimod. Despite subtherapeutic plasma bNAb levels, 36% (4/11) in the placebo/bNAb group compared to 0% (0/10) in the placebo/placebo group maintained virologic control after the 25-week ATI. Although immunotherapy with lefitolimod did not lead to ART-free HIV-1 control, bNAbs may be important components in future HIV-1 curative strategies. ClinicalTrials.gov identifier: NCT03837756.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:29 |
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| Enthalten in: |
Nature medicine - 29(2023), 10 vom: 01. Okt., Seite 2547-2558 |
| Sprache: |
Englisch |
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| Links: |
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| Anmerkungen: |
Date Completed 06.11.2023 Date Revised 09.03.2024 published: Print-Electronic ClinicalTrials.gov: NCT03837756 Citation Status MEDLINE |
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| doi: |
10.1038/s41591-023-02547-6 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 100 | 1 | |a Gunst, Jesper D |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Impact of a TLR9 agonist and broadly neutralizing antibodies on HIV-1 persistence |b the randomized phase 2a TITAN trial |
| 264 | 1 | |c 2023 | |
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| 500 | |a Date Revised 09.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a ClinicalTrials.gov: NCT03837756 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023. The Author(s). | ||
| 520 | |a Inducing antiretroviral therapy (ART)-free virological control is a critical step toward a human immunodeficiency virus type 1 (HIV-1) cure. In this phase 2a, placebo-controlled, double-blinded trial, 43 people (85% males) with HIV-1 on ART were randomized to (1) placebo/placebo, (2) lefitolimod (TLR9 agonist)/placebo, (3) placebo/broadly neutralizing anti-HIV-1 antibodies (bNAbs) or (4) lefitolimod/bNAb. ART interruption (ATI) started at week 3. Lefitolimod was administered once weekly for the first 8 weeks, and bNAbs were administered twice, 1 d before and 3 weeks after ATI. The primary endpoint was time to loss of virologic control after ATI. The median delay in time to loss of virologic control compared to the placebo/placebo group was 0.5 weeks (P = 0.49), 12.5 weeks (P = 0.003) and 9.5 weeks (P = 0.004) in the lefitolimod/placebo, placebo/bNAb and lefitolimod/bNAb groups, respectively. Among secondary endpoints, viral doubling time was slower for bNAb groups compared to non-bNAb groups, and the interventions were overall safe. We observed no added benefit of lefitolimod. Despite subtherapeutic plasma bNAb levels, 36% (4/11) in the placebo/bNAb group compared to 0% (0/10) in the placebo/placebo group maintained virologic control after the 25-week ATI. Although immunotherapy with lefitolimod did not lead to ART-free HIV-1 control, bNAbs may be important components in future HIV-1 curative strategies. ClinicalTrials.gov identifier: NCT03837756 | ||
| 650 | 4 | |a Clinical Trial, Phase II | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
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| 650 | 7 | |a Antibodies, Neutralizing |2 NLM | |
| 650 | 7 | |a Broadly Neutralizing Antibodies |2 NLM | |
| 650 | 7 | |a HIV Antibodies |2 NLM | |
| 650 | 7 | |a TLR9 protein, human |2 NLM | |
| 650 | 7 | |a Toll-Like Receptor 9 |2 NLM | |
| 650 | 7 | |a MGN1703 |2 NLM | |
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