Time to HIV rebound after antiretroviral therapy interruption: a double-blind randomised placebo-controlled trial of long-acting broadly neutralising antibodies; The RIO Trial.
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Lee Ming Jie, Cherrill Louise-Rae, Zacharopoulou Panagiota, Collins Simon, Fumagalli Marcilio, Falaschetti Emanuela, Altaf Mohammed, Tipoe Timothy, Godakandaarachi Piyumika, Fox Julie, Uriel Alison, Clarke Amanda, Loes Sabine Kinloch-de, Pett Sarah, Boffito Marta, Whitlock Gary, Søgaard Ole Schmeltz, Ring Kyle, Mangawa Irvine, Gohil Jesal, Elliott Tamara, Nielsen Henrik, Gunst Jesper Damsgaard, Orkin Chloe, Sutherland Rebecca, Hamzah Lisa, Cicconi Paola, Taylor Graham P, Ujetz Jacquie, Jahan Ishrat, Brown Helen, Robinson Nicola, Fletcher Stephen, Box Hanna, Seaton Kelly E, Tomaras Georgia, Ackerman Margaret E, Weiner Joshua A, Kaczynska Anna, Bittar Cintia, Horowitz Jill, Nussenzweig Michel Claudio, Caskey Marina, Frater John, Fidler Sarah
Аннотация
METHODS: RIO is a 1:1 randomised double-blind placebo-controlled trial of two LS-bNAbs (3BNC117-LS & 10-1074-LS) in individuals virally suppressed on ART initiated since early-stage HIV. Eligible participants interrupted ART after receiving blinded infusions of either both LS-bNAbs (Arm-A) or placebo (Arm-B). A second optional blinded infusion was offered after 20 weeks for participants who remained virally suppressed without ART. The primary outcome was time to viral rebound 20 weeks after ART interruption, defined as either the first of six consecutive plasma HIV RNA >1,000 copies/mL, or two measurements >100,000 copies/mL. Secondary outcomes included adverse events, long-term viral control and bNAb pharmacokinetics.
FINDINGS: Sixty-eight participants were randomised, thirty-four to each arm. By week 20, viral rebound had occurred in 8 Arm-A and 30 Arm-B participants; 75% (95% CI, 61 - 92) of Arm-A participants had not rebounded, compared to 11% (95% CI, 4-29) participants in Arm-B. Arm-A participants were 91% less likely to rebound compared to Arm-B participants (hazard ratio of rebound (HR): 0.09; 95% confidence interval (CI) 0.04 - 0.21, P < 0.001). ART-free viral control using the above endpoints beyond 96 weeks was evident in 7 (25%, 95% CI 13 - 48) Arm-A participants compared to 2 (11%, 95% CI 4 - 29) Arm-B participants (HR: 0.22, 95% CI 0.12 - 0.40, P < 0.001). These seven participants had predicted serum bNAb concentrations below the presumed therapeutic threshold of 10 μg/mL at 96 weeks. Of nine serious adverse events, none were study-related.
CONCLUSION: Long-acting bNAbs can sustain extended ART-free viral control in people treated during early-stage HIV and represent a promising step towards achieving ART-free HIV remission.