Completed Phase 3 study and submitted for approval
cabotegravir
Oral formulation of an integrase inhibitor mainly used for lead-in dose before long-acting formulation. From ViiV
cabotegravir LA/rilpivirine LA
An INSTI/NNRTI injection with very long half-life—detectable after more than one year following single injection. CAB LA / RPV LA injection studied for treatment, and CAB LA for prevention as single INSTI injection. From ViiV. See CAB LA/RPV LA in this guide.
fostemsavir (GSK3684934)
A gp120 attachment inhibitor. 48-week results from the Phase 3 BRIGHTE study in heavily treatment-experienced with extensive drug resistance. From ViiV. See fostemsavir in this guide.
Phase 3
leronlimab (PRO 140)
Monoclonal antibody CCR5 target. Once-weekly (350 mg) subcutaneous injection being studied in addition to ART for multi-drug resistance and as monotherapy maintenance therapy (without ART). From CytoDyn. See leronlimab in this guide.
UB-421
Monoclonal antibody CD4 binding. Infusion dosed either weekly or every two weeks as alternative to ART during treatment interruption. From United BioPharma.
Phase 1/2
MK-8591 (EFdA)
A new NRTI, highly potent, low dose, active against NRTI resistance. Long half-life, potential as oral (weekly dose) and implant (annual implant for PrEP). From Merck.
MK-8591/3TC/doravirine
Fixed-dose combination of the NNRTI doravirine plus generic 3TC and new NRTI MK-8591 (EFdA). From Merck.
GS-9131
A new NRTI active against NRTI resistance. Synergy reported with AZT, FTC, abacavir, efavirenz, bictegravir, dolutegravir and lopinavir; additive activity with TDF and TAF. Will be co-formulated with other Gilead drugs. Phase 2 dose-finding study in Ugandan women. From Gilead.
GSK3640254
A maturation inhibitor with Phase 2a results in HIV positive participants. From ViiV.
3BNC117 and 10-1074; PGDM1400 and PGT121; 10E8, etc. bNAb (broadly neutralizing antibody)
Many other bNAbs are in development, often in dual or triple combination and including trispecific molecules. (See “Scenes from the bNAb Revolution” in Jan + Feb 2020 issue). Potential as switch option without ART and in current studies for use as PrEP.
Phase 1 and pre-clinical
Combinectin (GSK3732394)
A gp41 / CD4 entry inhibitor. Combined adnectin/fusion inhibitor that stops viral entry by targeting multiple sites of action; potential for self-administered once-weekly injections. From ViiV.
GS-PI1
New once-daily unboosted protease inhibitor; high potency, long half-life, potential for fixed-dose combination single-tablet regimen. From Gilead.
GS-CA1
Early stage for a new drug class (capsid inhibitor) with activity at multiple stages of viral lifecycle. Subcutaneous injection with monthly or less frequent dosing. Phase 1 in HIV positive participants is ongoing. From Gilead.
MK-8583, MK-8527, MK-8558
NRTI and other drug class. These three compounds are registered for Phase 1 in HIV positive participants, with limited details on mechanisms of action. They are plausibly likely to have potential to be long-acting. From Merck.
Abbreviations
- 3TC: lamivudine
- bNAb: broadly neutralizing antibody
- AZT: zidovudine
- FDC: fixed-dose combination
- FTC: emtricitabine
- INSTI: integrase inhibitor
- mAb: monoclonal antibody
- NNRTI: non-nucleoside reverse transcriptase inhibitor
- NRTI: nucleoside reverse transcriptase inhibitor
- PI: protease inhibitor
- STR: single-tablet regimen
- TAF: tenofovir alafenamide
- TDF: tenofovir disoproxil fumarate
Adapted from HIV Pipeline 2019: New Drugs in Development, published by HIV i-Base, July 2019. For the full report, go to http://i-base.info/hiv-pipeline-report-2019/