TY - JOUR
T1 - Impact of a TLR9 agonist and broadly neutralizing antibodies on HIV-1 persistence
T2 - the randomized phase 2a TITAN trial
AU - Gunst, Jesper D.
AU - Højen, Jesper F.
AU - Pahus, Marie H.
AU - Rosás-Umbert, Miriam
AU - Stiksrud, Birgitte
AU - McMahon, James H.
AU - Denton, Paul W.
AU - Nielsen, Henrik
AU - Johansen, Isik S.
AU - Benfield, Thomas
AU - Leth, Steffen
AU - Gerstoft, Jan
AU - Østergaard, Lars
AU - Schleimann, Mariane H.
AU - Olesen, Rikke
AU - Støvring, Henrik
AU - Vibholm, Line
AU - Weis, Nina
AU - Dyrhol-Riise, Anne M.
AU - Pedersen, Karen B.H.
AU - Lau, Jillian S.Y.
AU - Copertino, Dennis C.
AU - Linden, Noemi
AU - Huynh, Tan T.
AU - Ramos, Victor
AU - Jones, R. Brad
AU - Lewin, Sharon R.
AU - Tolstrup, Martin
AU - Rasmussen, Thomas A.
AU - Nussenzweig, Michel C.
AU - Caskey, Marina
AU - Reikvam, Dag Henrik
AU - Søgaard, Ole S.
N1 - Publisher Copyright:
© 2023, The Author(s).
PY - 2023
Y1 - 2023
N2 - 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 .
AB - 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 .
U2 - 10.1038/s41591-023-02547-6
DO - 10.1038/s41591-023-02547-6
M3 - Journal article
C2 - 37696935
AN - SCOPUS:85170556818
VL - 29
SP - 2547
EP - 2558
JO - Nature Medicine
JF - Nature Medicine
SN - 1078-8956
IS - 10
ER -