Profile of cabotegravir and its potential in the treatment and prevention of HIV-1 infection: evidence to date

Thomas Whitfield, Adele Torkington, Clare van Halsema North West Infectious Diseases Unit, North Manchester General Hospital, Manchester, UK Abstract: Modern antiretroviral therapy has demonstrated effectiveness in preexposure prophylaxis (PrEP) and treatment of HIV infection. There is a demand for...

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Autores principales:	Whitfield T, Torkington A, van Halsema C
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	integrase inhibitor long-acting antiretroviral therapy pre-exposure prophylaxis Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/8204d9e6384e4f53af6f4a9c61f4bc63
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spelling	oai:doaj.org-article:8204d9e6384e4f53af6f4a9c61f4bc632021-12-02T11:53:34ZProfile of cabotegravir and its potential in the treatment and prevention of HIV-1 infection: evidence to date1179-1373https://doaj.org/article/8204d9e6384e4f53af6f4a9c61f4bc632016-10-01T00:00:00Zhttps://www.dovepress.com/profile-of-cabotegravir-and-its-potential-in-the-treatment-and-prevent-peer-reviewed-article-HIVhttps://doaj.org/toc/1179-1373Thomas Whitfield, Adele Torkington, Clare van Halsema North West Infectious Diseases Unit, North Manchester General Hospital, Manchester, UK Abstract: Modern antiretroviral therapy has demonstrated effectiveness in preexposure prophylaxis (PrEP) and treatment of HIV infection. There is a demand for prevention and treatment regimens that could overcome challenges of improving adherence, toxicity, and dosing convenience. Cabotegravir is an integrase strand transfer inhibitor and an analog of dolutegravir. Unlike dolutegravir, cabotegravir has a long half-life and can be formulated into a long-acting nanosuspension for parenteral administration. Initial pharmokinetic studies in humans have demonstrated adequate drug levels with intramuscular (IM) administration at 4 weekly and 8 weekly intervals, with few interactions with commonly used concomitant medications. Preliminary animal PrEP studies have shown that IM cabotegravir can prevent simian/HIV acquisition from rectal, vaginal, and intravenous challenge. Currently, there are two ongoing Phase II studies assessing cabotegravir as a PrEP agent in humans: ÉCLAIR and HPTN077. Cabotegravir has been studied in combination with rilpivirine as long-acting IM maintenance therapy. The Long-Acting Antiretroviral Treatment Enabling study demonstrated that those switching to oral cabotegravir/rilpivirine once virologically suppressed were more likely to maintain suppression than those continuing standard efavirenz-based therapy (82% vs 71% at 24 weeks). Initial results of the Long-Acting Antiretroviral Treatment Enabling-2 study of parenteral regimens found that 12 weeks after randomization to parenteral or oral regimens, there was no difference in proportions virologically suppressed on cabotegravir/rilpivirine daily orally vs IM every 4 weeks or 8 weeks (91% vs 94% vs 95%). The injections were well tolerated as, although they caused injection site pain in most recipients, most participants reported satisfaction with parenteral therapy. Cabotegravir offers a new member of the integrase strand transfer inhibitor class with potential for alternative mode of delivery. We await Phase III studies to define its efficacy and real-world experience to learn which patient groups stand to benefit most from the novel mode of delivery of treatment and PrEP. Keywords: integrase inhibitor, long-acting antiretroviral therapy, preexposure prophylaxisWhitfield TTorkington Avan Halsema CDove Medical Pressarticleintegrase inhibitor long-acting antiretroviral therapy pre-exposure prophylaxisImmunologic diseases. AllergyRC581-607ENHIV/AIDS: Research and Palliative Care, Vol Volume 8, Pp 157-164 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	integrase inhibitor long-acting antiretroviral therapy pre-exposure prophylaxis Immunologic diseases. Allergy RC581-607
spellingShingle	integrase inhibitor long-acting antiretroviral therapy pre-exposure prophylaxis Immunologic diseases. Allergy RC581-607 Whitfield T Torkington A van Halsema C Profile of cabotegravir and its potential in the treatment and prevention of HIV-1 infection: evidence to date
description	Thomas Whitfield, Adele Torkington, Clare van Halsema North West Infectious Diseases Unit, North Manchester General Hospital, Manchester, UK Abstract: Modern antiretroviral therapy has demonstrated effectiveness in preexposure prophylaxis (PrEP) and treatment of HIV infection. There is a demand for prevention and treatment regimens that could overcome challenges of improving adherence, toxicity, and dosing convenience. Cabotegravir is an integrase strand transfer inhibitor and an analog of dolutegravir. Unlike dolutegravir, cabotegravir has a long half-life and can be formulated into a long-acting nanosuspension for parenteral administration. Initial pharmokinetic studies in humans have demonstrated adequate drug levels with intramuscular (IM) administration at 4 weekly and 8 weekly intervals, with few interactions with commonly used concomitant medications. Preliminary animal PrEP studies have shown that IM cabotegravir can prevent simian/HIV acquisition from rectal, vaginal, and intravenous challenge. Currently, there are two ongoing Phase II studies assessing cabotegravir as a PrEP agent in humans: ÉCLAIR and HPTN077. Cabotegravir has been studied in combination with rilpivirine as long-acting IM maintenance therapy. The Long-Acting Antiretroviral Treatment Enabling study demonstrated that those switching to oral cabotegravir/rilpivirine once virologically suppressed were more likely to maintain suppression than those continuing standard efavirenz-based therapy (82% vs 71% at 24 weeks). Initial results of the Long-Acting Antiretroviral Treatment Enabling-2 study of parenteral regimens found that 12 weeks after randomization to parenteral or oral regimens, there was no difference in proportions virologically suppressed on cabotegravir/rilpivirine daily orally vs IM every 4 weeks or 8 weeks (91% vs 94% vs 95%). The injections were well tolerated as, although they caused injection site pain in most recipients, most participants reported satisfaction with parenteral therapy. Cabotegravir offers a new member of the integrase strand transfer inhibitor class with potential for alternative mode of delivery. We await Phase III studies to define its efficacy and real-world experience to learn which patient groups stand to benefit most from the novel mode of delivery of treatment and PrEP. Keywords: integrase inhibitor, long-acting antiretroviral therapy, preexposure prophylaxis
format	article
author	Whitfield T Torkington A van Halsema C
author_facet	Whitfield T Torkington A van Halsema C
author_sort	Whitfield T
title	Profile of cabotegravir and its potential in the treatment and prevention of HIV-1 infection: evidence to date
title_short	Profile of cabotegravir and its potential in the treatment and prevention of HIV-1 infection: evidence to date
title_full	Profile of cabotegravir and its potential in the treatment and prevention of HIV-1 infection: evidence to date
title_fullStr	Profile of cabotegravir and its potential in the treatment and prevention of HIV-1 infection: evidence to date
title_full_unstemmed	Profile of cabotegravir and its potential in the treatment and prevention of HIV-1 infection: evidence to date
title_sort	profile of cabotegravir and its potential in the treatment and prevention of hiv-1 infection: evidence to date
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/8204d9e6384e4f53af6f4a9c61f4bc63
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Profile of cabotegravir and its potential in the treatment and prevention of HIV-1 infection: evidence to date

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