Completed Phase 3 study and submitted for approval
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.
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.
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.
Monoclonal antibody CD4 binding. Infusion dosed either weekly or every two weeks as alternative to ART during treatment interruption. From United BioPharma.
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.
Fixed-dose combination of the NNRTI doravirine plus generic 3TC and new NRTI MK-8591 (EFdA). From Merck.
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.
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
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.
New once-daily unboosted protease inhibitor; high potency, long half-life, potential for fixed-dose combination single-tablet regimen. From Gilead.
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.
- 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/