Immunotherapeutic Approaches to HIV Cure and Remission

Ming J. Lee; S. Fidler; John Frater

Curr Opin Infect Dis. 2022;35(1):31-41.

Conclusion

It is likely that to achieve sustained HIV remission or cure, a multipronged approach involving a combination of enhancing both adaptive and innate immunity is required. Although this review is not exhaustive of all current immunotherapeutic approaches, it provides an overview of promising developments within the field towards a safe, effective, and durable HIV cure.

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Acknowledgements
This article is a discussion document and therefore represents the views of the co-authors, there is no specific funding associated with this work. M.J.L. acknowledge the Bill and Melinda Gates Foundation, which supports his salary through the university. J.F. and S.F. acknowledge funding from Oxford and Imperial College NIHR BRC respectively, which support their salaries through their university.

Financial support and sponsorship
This article is a discussion document and therefore represents the views of the co-authors, there is no specific funding associated with this work. M.J.L. acknowledge the Bill and Melinda Gates Foundation, which supports his salary through the university. J.F. and S.F. acknowledge funding from Oxford and Imperial College NIHR BRC respectively, which support their salaries through their university.

Table 1. Summary of current or future clinical trials involving combination bNAbs registered on clinicaltrials.gov [32]
Trial registration number	Intervention	Study design	PI, Sponsor	Start date	Primary endpoint
Trials assessing viral control as the primary outcome
NCT03837756TITAN	bNAbs: 3BNC117, 10–1074TLR9 agonist: Lefitolimod,	Phase II randomised placebo-controlled double blinded study n = 48	PI: Søgaard, Aarhus University Hospital, Denmark	May 2019	Time to HIV viral load >10 000 copies/ml x3 or end of ATI
NCT03707977	bNAbs: VRC01-LS, 10–1074	Phase I/II open label nonrandomised trial in children n = 40	PI: Shapiro, Kuritzkes, Licterfield, National Institute of Allergy and Infectious Diseases, USA (Study in Botswana)	Jun 2019	Safety Proportion with HIV viral load <400 copies/ml Proportion with HIV viral load <40 copies/ml
NCT03588715BEAT-2	bNAbs: 3BNC117, 10–1074Peg-IFN-a2b,	Phase I randomised open-label trial n = 21	PI: Montaner, University of Pennsylvania, USA	Jun 2020	Safety Frequency of HIV viral load < 50 copies/ml at week 8 after ATIInnate activation
NCT04250636	bNAbs: 3BNC117-LS, 10–1074-LS	Phase I open label single arm study n = 10	PI: Caskey, Rockefeller University, USA	Aug 2020	Safety Pharmacokinetics Decline in HIV viral load through week 4
NCT04357821	bNAbs: VRC07–523LS, 10–1074, Vaccines: IL-12 adjuvanted p24CE DNA prime, IL-12 adjuvanted DNA boost, MVA/HIV62B boost, TLR9 agonist: Lefitolimod	Phase I/II Single group open label combination intervention trial n = 20	PI: Deeks, University of California, USA	Aug 2020	Safety Proportion achieving post treatment control
NCT04319367	bNAbs: 10–1074-LS 3BNC117-LS	Phase II randomised placebo controlled double blinded study n = 72	Fidler, Imperial College London, UK	May 2021	Time to HIV viral rebound within 36 weeks of analytical treatment interruption.
NCT04340596	bNAbs: VRC07–523LS 10–1074 Il-15 superagonist: N-803	Phase I randomised open-label trial. n = 46	Wilkin, National Institute of Allergy and Infectious Disease, USA	May 2021	Safety, number of N-803 doses completed, proportion of participants with suppressed HIV viral load
NCT04983030	bNAbs: PGT121, PGDM1400, VRC07–523LS Vaccines: Ad26.Mos4.HIV MVA-BN-HIV	Phase I/II randomised double blinded study n = 36	PI: Juelg, Beth Israel Deaconess Medical Centre, USA	Aug 2021	Safety, T-cell and antibody responses, Proportion with HIV viral load <1000 copies/ml
Trials assessing safety as the primary outcome
NCT03571204	bNAbs: 3BNC117, 10–1074	Phase I triple-blinded randomised placebo-controlled trial n = 50	PI: Sneller, ational Institutes of Health Clinical Centre, Maryland, USA	Sep 2018	SafetyTolerability
NCT03554408	bNAbs: 10–1074-LS, 3BNC-117-LS	Phase I, dose escalation, first in man in HIV-negative and HIV-positive individuals. n = 75	Caskey, Rockefeller University, USA	Jun 2018	Safety and tolerability
NCT04173819	bNAbs: 3BNC117-LS 10–1074-LS	Phase I/II Randomised double-blinded placebo controlled trial n = 225	PI: Caskey, Rockefeller University, USA	Jan 2019	SafetyPharmacokinetics
NCT03705169	Trispecific bNAbSAR441236	Phase I randomised, double blinded study n = 84	PI: Tsibris, Kuritzkes, Tebas, National Institute of Allergy and Infectious Diseases, USA	Apr 2019	Safety, pharmacokinetics
NCT03875209	Bispecific bNAb: 10E8.4/iMab	Phase I randomised triple blinded study n = 63	PI: Ho, Bill and Melinda Gates Foundation, International AIDS Vaccine Initiative, USA, The Emmes Company, LLC	Apr 2019	Safety
NCT04811040	bNAbs: 3BNC117-LS (GS-5423) 10–1074-LS (GS-2872) Capsid inhibitor: Lenacapavir	Phase I randomised double blinded study n = 50	PI: Gilead Sciences	Apr 2021	Safety, Efficacy