Document Type
Article
Publication Date
9-11-2023
Publication Title
Nature Medicine
Volume
29
First Page
2547
Last Page
2558
Abstract
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.
Recommended Citation
Gunst, Jesper D.; Højen, Jesper Falkesgaard; Pahus, Marie H.; Rosás-Umbert, Miriam; Stiksrud, Birgitte; McMahon, James; Denton, Paul; Nielsen, Henrik; Johansen, Isik S.; Benfield, Thomas; Leth, Steffen; Gerstoft, Jan; Østergaard, Lars; Schleimann, Mariane H.; Olesen, Rikke; Støvring, Henrik; Vibholm, Line K.; Weis, Nia; Dyrhol-Riise, Anne M.; Pedersen, Karen B.H.; Lau, Jillian S.Y.; Copertino, Dennis C.; Linden, Noemi; Huynh, Tan T.; Ramos, Victor; Jones, Rl Brad; Lewin, Sharon R.; Tolstrup, Martin; Rasmussen, Thomas A.; Nussenzweig, Michel C.; Caskey, Marina; Reikvam, Dag Henrik; and Søgaard, Ole Schmeltz, "Impact of a TLR9 agonist and broadly neutralizing antibodies on HIV-1 persistence: the randomized phase 2a TITAN trial" (2023). Biology Faculty Publications. 194.
https://digitalcommons.unomaha.edu/biofacpub/194
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DOI https://doi.org/10.1038/s41591-023-02547-6