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HIV/AIDS
Published in Patricia G. Melloy, Viruses and Society, 2023
Like with other antiretroviral drug therapies, long-acting therapies are being tested now too to see if side effects are manageable, if they interact with other drugs, if they can be taken during pregnancy, and how quickly drug resistance develops (Gulick and Flexner 2019). In 2018, an intravaginal ring that can supply a long-acting version of antiretroviral therapy to females was developed (UNAIDS 2021a). A long-acting injectable antiretroviral therapy was approved by the Food and Drug Administration (FDA) in 2021. The injectable therapy, known as CABENUVA, is a combination of cabotegravir, an integrase inhibitor, and rilpivirine, a non-nucleoside reverse transcriptase inhibitor (FDA 2021; Healthcare 2021). Clinical trials yielded promising results for patients who started oral ART and then were switched to the long-acting therapy in the first long-acting injectable regimen (FLAIR) trial, as well as for patients on an oral therapy who switched to the long-acting drug to maintain their suppression of HIV in the antiretroviral therapy as long-acting suppression (ATLAS) trial for either four or eight weeks (Orkin et al. 2020; Swindells et al. 2020; Rizzardini et al. 2020; Gulick and Flexner 2019; Overton et al. 2021; Rial-Crestelo, Pinto-Martínez, and Pulido 2020).
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
Cabotegravir (CAB-LA) is now under development by ViiV for both HIV prevention and treatment. It is a long-acting integrase strand transfer inhibitor that can be administered intramuscularly providing 2–3 months of effective blood levels. It can also be administered orally and via subcutaneous injection. Phase IIa clinical trials are under way. The LATTE 2 trial has assessed the efficacy of a combination of long-acting cabotegravir in combination with long-acting rilpivirine given by intramuscular injection every 4 or 8 weeks as simplified maintenance in 286 HIV-infected individuals with virologic suppression after 20 weeks of oral cabotegravir plus abacavir–lamivudine. Of these, 95% and 94% receiving eight and four weekly injections, respectively, maintained a viral load of < 20 copies/ml at week 32. Mild to moderate injection site reactions occurred in > 90% of recipients, but very few patients withdrew from the study because of these reactions. Two studies are planned to start soon (NCT02478463 and NCT02720094). (Andrews et al., 2015; Bowers et al., 2016; Landovitz et al., 2016; Margolis et al., 2015; Trezza et al., 2015; Margolis et al., 2016).
Investigational drugs for HIV: trends, opportunities and key players
Published in Expert Opinion on Investigational Drugs, 2023
Ronald J. Overmars, Zoë Krullaars, Thibault Mesplède
The integrase strand transfer inhibitor cabotegravir can be administered via intramuscular injection every two months with and without an oral lead-in phase. Unlike bNAbs, this six-times yearly antiviral drug does not necessitate challenging pre-treatment susceptibility screening, nor is it highly susceptible to the development of resistance mutations. It effectively reduces viremia below detectable levels with confirmed virological failure in only 1.4% (n = 23/1,651) of people over three years [55]. Besides other formulations, cabotegravir can be administered by injections alone for prevention or in combination with the non-nucleoside reverse transcriptase inhibitor rilpivirine to treat HIV infection. It was reviewed recently [56,57], so we focused on recent findings and developments.
A literature review of the patent application publications on cabotegravir – an HIV integrase strand transfer inhibitor
Published in Expert Opinion on Therapeutic Patents, 2020
Cabotegravir is an integrase strand transfer inhibitor that is currently in clinical study for both oral lead-in and long-acting parenteral application [25]. It is mostly developed for HIV treatment and prophylaxis (PrEP). However, according to patent application CN 109646440 A [70], filled and published in 2019, it could also be used in veterinary pharmacy against infection with bovine infectious rhinotracheitis virus. Cabotegravir has not yet been approved for use as PrEP or treatment of HIV infection, but on-going clinical studies are showing promising results for use of cabotegravir as long-acting HIV medication, thus reducing the pill burden and enhancing the patient compliance [24]. The original synthesis route and the manufacturing synthetic route were provided in the patent by Shionogi & Co., Ltd. [46]. However, in past years different route of synthesis have been found and are reviewed in article by David L. Hughes [51]. Cabotegravir is mainly studied for the treatment and prophylaxis of HIV infection. Besides the single agent as long-acting formulation for prophylaxis, the use of cabotegravir is also explored in combination with different classes of antiretroviral agents such as non-nucleoside reverse transcriptase inhibitor rilpivirine [57] and nucleotide reverse transcriptase inhibitor tenofovir alafenamide [58,67] for treatment of HIV infection. However, there are several patent applications claiming the method of treatment with cabotegravir and one or two additional antiretroviral drugs from different classes, but no experimental data are presented.
Safety review of tenofovir disoproxil fumarate/emtricitabine pre-exposure prophylaxis for pregnant women at risk of HIV infection
Published in Expert Opinion on Drug Safety, 2021
Randy M. Stalter, Jillian Pintye, Kenneth K. Mugwanya
Recently, the HPTN 084 study of long-acting injectable cabotegravir (CAB-LA), an HIV integrase strand transfer inhibitor, demonstrated that CAB-LA given once every eight weeks was safe and superior to daily oral TDF/FTC for HIV prevention among cisgender women [66]. CAB-LA, when it gets regulatory approval, could be instrumental to overcoming the challenges observed with daily adherence to TDF/FTC. Limited data from 13 women who became pregnant after exposure to oral or injectable cabotegravir during Phase 2/3 studies show that four resulted in live births, two resulted in spontaneous abortion, two in medical or induced abortion and one possible early miscarriage [67]. It is unclear how these reported frequencies compare to those in the underlying population.