Table 2.
Selected Investigational Treatments for HIV Infection
| Agent (Manufacturer/Sponsor) | Description/Mechanism of Action | Indications/Comments | Status |
|---|---|---|---|
| Albuvirtide (Frontier Biotechnologies Co., Ltd.) | Fusion inhibitor; a synthetic peptide that works by binding to the HIV gp41 envelope protein | Developed primarily for China’s national Free Antiretroviral Treatment Program; once-weekly infusion | Phase 3 |
| Bictegravir 50 mg, emtricitabine 200 mg, and tenofovir alafenamide 25 mg (Gilead Sciences) | Bictegravir, a novel INSTI, inhibits strand transfer of viral DNA into host genome and thus prevents HIV-1 replication. In vitro, it has potent antiviral activity against HIV-2 and subtypes of wild-type HIV-1. Has shown synergistic effects in combination with other ARVs, including the dual-NRTI backbone of tenofovir alafenamide and emtricitabine, as well as darunavir | Does not require boosting and can be taken with or without food | NDA filed (target action date, February 12, 2018) |
| Cabotegravir (ViiV Healthcare) | INSTI; an analogue of dolutegravir that prevents viral DNA integration into the host genome and inhibits HIV replication | Being developed for both HIV treatment and HIV prevention | Phase 3 |
| Darunavir 800 mg, cobicistat 150 mg, emtricitabine 200 mg, and tenofovir alafenamide 10 mg (Janssen) | First protease inhibitor-based single-tablet regimen. Darunavir is a protease inhibitor, cobicistat is a pharmacokinetic enhancer, and emtricitabine and tenofovir alafenamide are NRTIs | High barrier to resistance (due to darunavir/ cobicistat), with potentially less renal and bone toxicity compared with regimens that include TDF; potential gastrointestinal adverse effects; potential drug interactions secondary to the cobicistat component | NDA filed |
| Dolutegravir plus lamivudine (ViiV Healthcare) | Dolutegravir is a potent INSTI; lamivudine is a nucleoside analogue | Reported safe and effective as maintenance therapy at Conference on Retroviruses and Opportunistic Infections 2017 | Phase 3 |
| Doravirine (Merck) | Novel NNRTI with in vitro activity against wild-type HIV-1 and common NNRTI- resistant mutant viruses. Resistance to doravirine has been observed with several NNRTI-resistant mutations, including Y188L | Once-daily use being evaluated individually or in a fixed-dose combination with generic lamivudine and TDF. The combination is anticipated to cost less than similar combinations containing fewer generic components | Phase 3 |
| Fostemsavir (ViiV Healthcare) | A prodrug of temsavir; a first-in-class attachment inhibitor that binds directly to HIV-1 gp120, preventing initial viral attachment and entry into host CD4+ T cells | For patients with multidrug-resistant HIV | Phase 3 |
| Ibalizumab (TaiMed Biologics and Theratechnologies) | Monoclonal antibody that blocks initial HIV entry into cells by attaching to CD4 receptors | Biologic developed for the treatment of cross-class/multidrug-resistant HIV. Will require intravenous infusions (800 mg) every two weeks | BLA filed; approval anticipated in first half of 2018 |
| PRO140 (CytoDyn, Inc.) | HIV-1 entry inhibitor; humanized IgG4 monoclonal antibody inhibits CCR5-mediated HIV-1 viral entry | Once-weekly subcutaneous injection for maintenance of viral suppression | Phase 3 |
| Rilpivirine (Janssen) and cabotegravir (ViiV Healthcare) | Rilpivirine is an NNRTI; cabotegravir is an INSTI | Combination of two long-acting formulations for intramuscular injection. Phase 3 studies are evaluating dosing every four weeks | Phase 3 |
ARV = antiretroviral; BLA = biologics license application; HIV = human immunodeficiency virus; INSTI = integrase strand transfer inhibitor; NDA = new drug application; NNRTI = non-nucleoside reverse transcriptase inhibitor; NRTI = nucleotide reverse transcriptase inhibitor; TDF = tenofovir disoproxil fumarate. Sources: National Institutes of Health (via https://aidsinfo.nih.gov); manufacturers’ websites; meeting abstracts.