Onyema Ogbuagu

Novel ART or ART combinations can address critical unmet needs, such as simplifying treatment for treatment-experienced people with HIV, with or without drug resistance, and post-exposure prophylaxis regimens for HIV-exposed individuals. Novel long-acting (LA) ART delivery approaches could be adapted to expand uptake, improve tolerability and logistics of their administration.

Prof. Segal-Maurer (New York-Presbyterian Queens, USA) presented 48-week data of a proof-of-concept randomized Phase 2 trial of oral single-tablet fixed-dose INSTI-capsid inhibitor combinations containing bictegravir-lenacapavir (BIC-LEN), showing high maintenance of virologic suppression (VS) in people with HIV previously on complex ART. Notably, people with hepatitis B were excluded. Larger Phase 3 studies evaluating BIC-LEN for broader categories of VS-PWH are underway. Luise Rogg (ViiV), presented data on early characterization of a promising novel 3rd generation INSTI (VH-184), showing remarkable antiviral potency against DTG-selected HIV-1 INSTI-resistant isolates. Safety profile was acceptable; larger phase 2 studies planned and novel LA formulations are in clinical development. Gabriella Scarlatti (IRCCS Ospedale San Raffaele, Italy) and colleagues assessed single dose of bNAbs - VRC07-523LS (CD4) or CAP256V2LS (V2 apex) as post-exposure prophylaxis within 96 hours of birth for HIV-exposed (and breastfed) infants (in combination with ART). Reactogenicity events occurred but were generally low grade, and laboratory adverse events related to study drug included elevated transaminases but were asymptomatic and resolved within 14 days. Pharmacokinetic parameters suggest 3-month dosing needed, but the breadth of the agents is not 100%. Subcutaneous administration of cabotegravir-rilpivirine had similar PK to IM dosing but was not preferred by study participants.

The “nucleoside(tide)-sparing” BIC-LEN holds promise to simplify treatment, mitigate some safety and tolerability concerns for individuals on complex ART. Arguably, it should be explored further as a solution to the anticipated increase of INSTI-based treatment failures. If the 3rd generation INSTI, VH-184 succeeds, it could be an attractive component of future regimens to address the same problem. Long-acting PEP is an exciting development, logistically appealing, and inherently addresses the problem with treatment completion rates, but careful selection of agents is warranted so as not to jeopardize efficacy. Moderator, Chloe Orkin, advocated for LA-ART to be made affordably available to LMICs.