Impact of a TLR9 agonist and broadly neutralizing antibodies on HIV-1 persistence: the randomized phase 2a TITAN trial

Jesper D. Gunst, Jesper F. Højen, Marie H. Pahus, Miriam Rosás-Umbert, Birgitte Stiksrud, James H. McMahon, Paul W. Denton, Henrik Nielsen, Isik S. Johansen, Thomas Benfield, Steffen Leth, Jan Gerstoft, Lars Østergaard, Mariane H. Schleimann, Rikke Olesen, Henrik Støvring, Line Vibholm, Nina Weis, Anne M. Dyrhol-Riise, Karen B.H. PedersenJillian S.Y. Lau, Dennis C. Copertino, Noemi Linden, Tan T. Huynh, Victor Ramos, R. Brad Jones, Sharon R. Lewin, Martin Tolstrup, Thomas A. Rasmussen, Michel C. Nussenzweig, Marina Caskey, Dag Henrik Reikvam, Ole S. Søgaard*

*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review


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. identifier: NCT03837756 .

Original languageEnglish
JournalNature Medicine
Pages (from-to)2547-2558
Number of pages12
Publication statusPublished - Oct 2023


  • Adjuvants, Immunologic
  • Antibodies, Neutralizing
  • Broadly Neutralizing Antibodies
  • Female
  • HIV Antibodies/therapeutic use
  • HIV Infections
  • HIV-1
  • Humans
  • Male
  • Toll-Like Receptor 9/therapeutic use


Dive into the research topics of 'Impact of a TLR9 agonist and broadly neutralizing antibodies on HIV-1 persistence: the randomized phase 2a TITAN trial'. Together they form a unique fingerprint.

Cite this