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Investigational Antiviral Drugs
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
John Mills, Suzanne M. Crowe, Marianne Martinello
Ibalizumab (TMB-335, TNX-355, Hu5A8) is an anti-CD4 monoclonal antibody that blocks entry of HIV-1. It has broad and potent antiviral activity in vitro and in vivo. Median in vitro neutralization potency assessed by EC50 was 0.03 ug/ml. Early clinical trials of monotherapy resulted in a 10-fold reduction in HIV viral load. Preliminary results from current studies suggest efficacy with 82% of patients with multidrug-resistant HIV infection achieving the primary end point of a decrease of at least 0.5 log10 HIV RNA copies/ml after 7 days of treatment. Two phase III trials are under way (NCT02707861 and NCT02475629) (Mazor et al., 2015; Pace and Markowitz, 2015).
Investigational drugs for HIV: trends, opportunities and key players
Published in Expert Opinion on Investigational Drugs, 2023
Ronald J. Overmars, Zoë Krullaars, Thibault Mesplède
Before discussing broadly neutralizing antibodies, it is worth noting that another antibody that does not belong to this drug class, ibalizumab, was approved for clinical use by people with multidrug-resistant HIV-1 infection in 2018 [38,39]. Ibalizumab is a humanized IgG4 monoclonal antibody that targets CD4 to prevent post-attachment conformational changes induced by HIV-1 gp120 that are necessary for fusion without impairing T-cell functions [40–43]. Ibalizumab is administered by intravenous injections of a 2 g loading dose followed by 800 mg doses every two weeks but other schemes have been studied [44].The most exciting recent development regarding ibalizumab was the demonstration that this drug is active in vitro against HIV-2 viruses from both groups A and B [45]. This is a positive development since people with HIV-2 have limited therapeutic options.
Emerging drugs for the treatment of HIV/AIDS: a review of 2019/2020 phase II and III trials
Published in Expert Opinion on Emerging Drugs, 2021
Marco Piscaglia, Maria Vittoria Cossu, Matteo Passerini, Francesco Petri, Martina Gerbi, Chiara Fusetti, Amedeo Capetti, Giuliano Rizzardini
Ibalizumab is the first monoclonal antibody approved and introduced into clinical practice for the treatment of multidrug-resistant HIV in failing patients. Several others are in Phase 1 studies [54]. Only one monoclonal antibody, UB-421, and one bNAb, VRC01, have been studied in a phase 2 trial in the past 2 years. Similar to ibalizumab [66], UB-421 showed good antiviral potency with a 1–2log10 reduction in viral load. In addition, no resistance was observed but larger cohorts are needed to confirm this finding. VRC01 did not show efficacy in maintaining viral suppression in monotherapy in the study analyzed, although it had shown better results in phase 1 studies. Also a recently published trial regarding its use in prophylaxis did not reach the efficacy outcome [67]. It is important to note that the presence of antibody resistance has been shown both a priori, even before infusion, and even an emerging resistance to antibodies at subsequent analysis [57,68]. The research on this emerging technology should focus on a combined approach that has already offered some interesting results, especially in patients with low viremia [69].
Acceptability and preferences for long-acting antiretroviral formulations among people with HIV infection
Published in AIDS Care, 2021
Dima Dandachi, Bich N. Dang, Brandon Lucari, Susan Swindells, Thomas P. Giordano
Various long-acting (LA) injectable antiretrovirals are being developed for the treatment and prevention of HIV (Hassounah & Mesplède, 2018; Nyaku et al., 2017). These LA regimens hold promise because they do not depend on daily adherence from the patient. LA injectable ART have an extended half-life that permit monthly or even less frequent administration (Rusconi et al., 2017). The LATTE-2 phase 2b study showed LA ART were as effective as the oral regimen for maintenance of HIV viral suppression (Margolis et al., 2017). Two phase III studies, ATLAS and FLAIR, presented at the 2019 Conference on Retroviruses and Opportunistic Infections demonstrated the efficacy and safety of cabotegravir and rilpivirine as a LA injectable ART option for people with HIV (PWH), either on switching from oral therapy, or as initial therapy (Swindells et al., March 4 - 7, 2019). Subdermal implants delivering antiretrovirals by sustained release are in earlier stages of development (Chen et al., 2005; Flexner et al., 2019; Gunawardana et al., 2015). In 2018, the FDA approved ibalizumab, the first approved antiretroviral medication delivered via intravenous infusion every two weeks, as an add-on treatment for experienced patients with multidrug-resistant HIV (Emu et al., 2018; FDA, 2018).