Safety, tolerability and impact on viral reservoirs of the addition to antiretroviral therapy of ABX464, an investigational antiviral drug, in individuals living with HIV-1: a Phase IIa randomised controlled study
Objectives: To assess the safety and tolerability as well as antiretroviral impact of ABX464, an oral investigational drug with a novel mechanism of HIV-1 inhibition (ClinicalTrials.gov NCT02735863). Methods: Randomised, double-blind, placebo-controlled, Phase IIa study in individuals living with HI...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Sofie Rutsaert [verfasserIn] Jean-Marc Steens [verfasserIn] Paul Gineste [verfasserIn] Basiel Cole [verfasserIn] Sam Kint [verfasserIn] P. Noel Barrett [verfasserIn] Jamal Tazi [verfasserIn] Didier Scherrer [verfasserIn] Hartmut J. Ehrlich [verfasserIn] Linos Vandekerckhove [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2019 |
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| Schlagwörter: |
ABX464, safety, tolerability, HIV-1, Phase IIa study, HIV-1 reservoirs, viral rebound |
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| Übergeordnetes Werk: |
In: Journal of Virus Eradication - Elsevier, 2021, 5(2019), 1, Seite 10-22 |
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| Übergeordnetes Werk: |
volume:5 ; year:2019 ; number:1 ; pages:10-22 |
| Links: |
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| DOI / URN: |
10.1016/S2055-6640(20)30273-9 |
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| Katalog-ID: |
DOAJ058998829 |
|---|
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| 245 | 1 | 0 | |a Safety, tolerability and impact on viral reservoirs of the addition to antiretroviral therapy of ABX464, an investigational antiviral drug, in individuals living with HIV-1: a Phase IIa randomised controlled study |
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| 520 | |a Objectives: To assess the safety and tolerability as well as antiretroviral impact of ABX464, an oral investigational drug with a novel mechanism of HIV-1 inhibition (ClinicalTrials.gov NCT02735863). Methods: Randomised, double-blind, placebo-controlled, Phase IIa study in individuals living with HIV-1 on antiretroviral therapy at six clinical centres in Spain, France and Belgium. ABX464 was administered once a day to 22 fully controlled HIV-1-positive participants at two doses (50 mg, n=6 and 150 mg, n=16) versus placebo, which was given to eight participants for 28 days in combination with a boosted protease inhibitor (darunavir/ritonavir or darunavir/cobicistat). The primary objective of the study was to assess ABX464 safety and tolerability when used in combination with darunavir boosted therapy. The secondary objective was to study antiretroviral efficacy on viral reservoirs using time to viral rebound following treatment interruption. The impact of ABX464 on HIV-1 reservoirs was further assessed by measuring levels of total HIV-1 in peripheral blood mononuclear cells (PBMCs) in the intervention arm versus placebo. A positive response was defined as an absolute reduction in HIV-1 DNA of at least 50 copies/106 PBMCs and a relative decrease <25% of HIV-1 DNA level. Results: Twenty-six of the 30 randomly allocated participants completed the study according to the study protocol. ABX464 was found to be safe and well tolerated with the majority of adverse events (AEs) being mild or moderate. Of the participants, 22 (73.3%) experienced treatment-associated AEs (93.8%, 66.7%, 37.5% in the ABX464 150-mg, 50-mg dose and placebo arms, respectively). Percentages for combined grade 3/4 AEs for the three arms were 6.3%, 0% and 12.5%, respectively.Median time (Kaplan–Meier estimates) to viral rebound for ABX464 150-mg, 50-mg and placebo arms were 12.0 (95% confidence interval [CI]: 10–15), 15.5 (95% CI 14–22) and 15.5 (95% CI 1–22) days, respectively with no significant difference between the 150-mg treatment arm and placebo.Median changes in total HIV-1 DNA copies/106 PBMCs for ABX464 150-mg, 50-mg and placebo arms after 28 days of treatment were −40 (range −434 to +194), −115 (range −116 to −114) and 25 (range −35 to +218), respectively, showing a decrease in the intervention arms. There were 6/14, 2/2, and 0/4 responders for ABX464 150 mg, 50 mg and placebo, respectively. No significant difference was seen between treatment arms and placebo with respect to these virological parameters. Conclusions: This small controlled study confirmed the good safety and tolerability of ABX464 and provides some evidence of a potential reduction of the HIV-1 reservoir in terms of HIV-1 DNA levels in PBMCs when it was added to an HIV-1 protease inhibitor-based regimen. These results will need to be confirmed in a larger study. | ||
| 650 | 4 | |a ABX464, safety, tolerability, HIV-1, Phase IIa study, HIV-1 reservoirs, viral rebound | |
| 653 | 0 | |a Microbiology | |
| 653 | 0 | |a Public aspects of medicine | |
| 700 | 0 | |a Jean-Marc Steens |e verfasserin |4 aut | |
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| 700 | 0 | |a Basiel Cole |e verfasserin |4 aut | |
| 700 | 0 | |a Sam Kint |e verfasserin |4 aut | |
| 700 | 0 | |a P. Noel Barrett |e verfasserin |4 aut | |
| 700 | 0 | |a Jamal Tazi |e verfasserin |4 aut | |
| 700 | 0 | |a Didier Scherrer |e verfasserin |4 aut | |
| 700 | 0 | |a Hartmut J. Ehrlich |e verfasserin |4 aut | |
| 700 | 0 | |a Linos Vandekerckhove |e verfasserin |4 aut | |
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10.1016/S2055-6640(20)30273-9 doi (DE-627)DOAJ058998829 (DE-599)DOAJ3ef3f0db63364cc288365e8f7330998c DE-627 ger DE-627 rakwb eng QR1-502 RA1-1270 Sofie Rutsaert verfasserin aut Safety, tolerability and impact on viral reservoirs of the addition to antiretroviral therapy of ABX464, an investigational antiviral drug, in individuals living with HIV-1: a Phase IIa randomised controlled study 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Objectives: To assess the safety and tolerability as well as antiretroviral impact of ABX464, an oral investigational drug with a novel mechanism of HIV-1 inhibition (ClinicalTrials.gov NCT02735863). Methods: Randomised, double-blind, placebo-controlled, Phase IIa study in individuals living with HIV-1 on antiretroviral therapy at six clinical centres in Spain, France and Belgium. ABX464 was administered once a day to 22 fully controlled HIV-1-positive participants at two doses (50 mg, n=6 and 150 mg, n=16) versus placebo, which was given to eight participants for 28 days in combination with a boosted protease inhibitor (darunavir/ritonavir or darunavir/cobicistat). The primary objective of the study was to assess ABX464 safety and tolerability when used in combination with darunavir boosted therapy. The secondary objective was to study antiretroviral efficacy on viral reservoirs using time to viral rebound following treatment interruption. The impact of ABX464 on HIV-1 reservoirs was further assessed by measuring levels of total HIV-1 in peripheral blood mononuclear cells (PBMCs) in the intervention arm versus placebo. A positive response was defined as an absolute reduction in HIV-1 DNA of at least 50 copies/106 PBMCs and a relative decrease <25% of HIV-1 DNA level. Results: Twenty-six of the 30 randomly allocated participants completed the study according to the study protocol. ABX464 was found to be safe and well tolerated with the majority of adverse events (AEs) being mild or moderate. Of the participants, 22 (73.3%) experienced treatment-associated AEs (93.8%, 66.7%, 37.5% in the ABX464 150-mg, 50-mg dose and placebo arms, respectively). Percentages for combined grade 3/4 AEs for the three arms were 6.3%, 0% and 12.5%, respectively.Median time (Kaplan–Meier estimates) to viral rebound for ABX464 150-mg, 50-mg and placebo arms were 12.0 (95% confidence interval [CI]: 10–15), 15.5 (95% CI 14–22) and 15.5 (95% CI 1–22) days, respectively with no significant difference between the 150-mg treatment arm and placebo.Median changes in total HIV-1 DNA copies/106 PBMCs for ABX464 150-mg, 50-mg and placebo arms after 28 days of treatment were −40 (range −434 to +194), −115 (range −116 to −114) and 25 (range −35 to +218), respectively, showing a decrease in the intervention arms. There were 6/14, 2/2, and 0/4 responders for ABX464 150 mg, 50 mg and placebo, respectively. No significant difference was seen between treatment arms and placebo with respect to these virological parameters. Conclusions: This small controlled study confirmed the good safety and tolerability of ABX464 and provides some evidence of a potential reduction of the HIV-1 reservoir in terms of HIV-1 DNA levels in PBMCs when it was added to an HIV-1 protease inhibitor-based regimen. These results will need to be confirmed in a larger study. ABX464, safety, tolerability, HIV-1, Phase IIa study, HIV-1 reservoirs, viral rebound Microbiology Public aspects of medicine Jean-Marc Steens verfasserin aut Paul Gineste verfasserin aut Basiel Cole verfasserin aut Sam Kint verfasserin aut P. Noel Barrett verfasserin aut Jamal Tazi verfasserin aut Didier Scherrer verfasserin aut Hartmut J. Ehrlich verfasserin aut Linos Vandekerckhove verfasserin aut In Journal of Virus Eradication Elsevier, 2021 5(2019), 1, Seite 10-22 (DE-627)867995882 (DE-600)2868549-0 20556659 nnns volume:5 year:2019 number:1 pages:10-22 https://doi.org/10.1016/S2055-6640(20)30273-9 kostenfrei https://doaj.org/article/3ef3f0db63364cc288365e8f7330998c kostenfrei http://www.sciencedirect.com/science/article/pii/S2055664020302739 kostenfrei https://doaj.org/toc/2055-6640 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 5 2019 1 10-22 |
| spelling |
10.1016/S2055-6640(20)30273-9 doi (DE-627)DOAJ058998829 (DE-599)DOAJ3ef3f0db63364cc288365e8f7330998c DE-627 ger DE-627 rakwb eng QR1-502 RA1-1270 Sofie Rutsaert verfasserin aut Safety, tolerability and impact on viral reservoirs of the addition to antiretroviral therapy of ABX464, an investigational antiviral drug, in individuals living with HIV-1: a Phase IIa randomised controlled study 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Objectives: To assess the safety and tolerability as well as antiretroviral impact of ABX464, an oral investigational drug with a novel mechanism of HIV-1 inhibition (ClinicalTrials.gov NCT02735863). Methods: Randomised, double-blind, placebo-controlled, Phase IIa study in individuals living with HIV-1 on antiretroviral therapy at six clinical centres in Spain, France and Belgium. ABX464 was administered once a day to 22 fully controlled HIV-1-positive participants at two doses (50 mg, n=6 and 150 mg, n=16) versus placebo, which was given to eight participants for 28 days in combination with a boosted protease inhibitor (darunavir/ritonavir or darunavir/cobicistat). The primary objective of the study was to assess ABX464 safety and tolerability when used in combination with darunavir boosted therapy. The secondary objective was to study antiretroviral efficacy on viral reservoirs using time to viral rebound following treatment interruption. The impact of ABX464 on HIV-1 reservoirs was further assessed by measuring levels of total HIV-1 in peripheral blood mononuclear cells (PBMCs) in the intervention arm versus placebo. A positive response was defined as an absolute reduction in HIV-1 DNA of at least 50 copies/106 PBMCs and a relative decrease <25% of HIV-1 DNA level. Results: Twenty-six of the 30 randomly allocated participants completed the study according to the study protocol. ABX464 was found to be safe and well tolerated with the majority of adverse events (AEs) being mild or moderate. Of the participants, 22 (73.3%) experienced treatment-associated AEs (93.8%, 66.7%, 37.5% in the ABX464 150-mg, 50-mg dose and placebo arms, respectively). Percentages for combined grade 3/4 AEs for the three arms were 6.3%, 0% and 12.5%, respectively.Median time (Kaplan–Meier estimates) to viral rebound for ABX464 150-mg, 50-mg and placebo arms were 12.0 (95% confidence interval [CI]: 10–15), 15.5 (95% CI 14–22) and 15.5 (95% CI 1–22) days, respectively with no significant difference between the 150-mg treatment arm and placebo.Median changes in total HIV-1 DNA copies/106 PBMCs for ABX464 150-mg, 50-mg and placebo arms after 28 days of treatment were −40 (range −434 to +194), −115 (range −116 to −114) and 25 (range −35 to +218), respectively, showing a decrease in the intervention arms. There were 6/14, 2/2, and 0/4 responders for ABX464 150 mg, 50 mg and placebo, respectively. No significant difference was seen between treatment arms and placebo with respect to these virological parameters. Conclusions: This small controlled study confirmed the good safety and tolerability of ABX464 and provides some evidence of a potential reduction of the HIV-1 reservoir in terms of HIV-1 DNA levels in PBMCs when it was added to an HIV-1 protease inhibitor-based regimen. These results will need to be confirmed in a larger study. ABX464, safety, tolerability, HIV-1, Phase IIa study, HIV-1 reservoirs, viral rebound Microbiology Public aspects of medicine Jean-Marc Steens verfasserin aut Paul Gineste verfasserin aut Basiel Cole verfasserin aut Sam Kint verfasserin aut P. Noel Barrett verfasserin aut Jamal Tazi verfasserin aut Didier Scherrer verfasserin aut Hartmut J. Ehrlich verfasserin aut Linos Vandekerckhove verfasserin aut In Journal of Virus Eradication Elsevier, 2021 5(2019), 1, Seite 10-22 (DE-627)867995882 (DE-600)2868549-0 20556659 nnns volume:5 year:2019 number:1 pages:10-22 https://doi.org/10.1016/S2055-6640(20)30273-9 kostenfrei https://doaj.org/article/3ef3f0db63364cc288365e8f7330998c kostenfrei http://www.sciencedirect.com/science/article/pii/S2055664020302739 kostenfrei https://doaj.org/toc/2055-6640 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 5 2019 1 10-22 |
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10.1016/S2055-6640(20)30273-9 doi (DE-627)DOAJ058998829 (DE-599)DOAJ3ef3f0db63364cc288365e8f7330998c DE-627 ger DE-627 rakwb eng QR1-502 RA1-1270 Sofie Rutsaert verfasserin aut Safety, tolerability and impact on viral reservoirs of the addition to antiretroviral therapy of ABX464, an investigational antiviral drug, in individuals living with HIV-1: a Phase IIa randomised controlled study 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Objectives: To assess the safety and tolerability as well as antiretroviral impact of ABX464, an oral investigational drug with a novel mechanism of HIV-1 inhibition (ClinicalTrials.gov NCT02735863). Methods: Randomised, double-blind, placebo-controlled, Phase IIa study in individuals living with HIV-1 on antiretroviral therapy at six clinical centres in Spain, France and Belgium. ABX464 was administered once a day to 22 fully controlled HIV-1-positive participants at two doses (50 mg, n=6 and 150 mg, n=16) versus placebo, which was given to eight participants for 28 days in combination with a boosted protease inhibitor (darunavir/ritonavir or darunavir/cobicistat). The primary objective of the study was to assess ABX464 safety and tolerability when used in combination with darunavir boosted therapy. The secondary objective was to study antiretroviral efficacy on viral reservoirs using time to viral rebound following treatment interruption. The impact of ABX464 on HIV-1 reservoirs was further assessed by measuring levels of total HIV-1 in peripheral blood mononuclear cells (PBMCs) in the intervention arm versus placebo. A positive response was defined as an absolute reduction in HIV-1 DNA of at least 50 copies/106 PBMCs and a relative decrease <25% of HIV-1 DNA level. Results: Twenty-six of the 30 randomly allocated participants completed the study according to the study protocol. ABX464 was found to be safe and well tolerated with the majority of adverse events (AEs) being mild or moderate. Of the participants, 22 (73.3%) experienced treatment-associated AEs (93.8%, 66.7%, 37.5% in the ABX464 150-mg, 50-mg dose and placebo arms, respectively). Percentages for combined grade 3/4 AEs for the three arms were 6.3%, 0% and 12.5%, respectively.Median time (Kaplan–Meier estimates) to viral rebound for ABX464 150-mg, 50-mg and placebo arms were 12.0 (95% confidence interval [CI]: 10–15), 15.5 (95% CI 14–22) and 15.5 (95% CI 1–22) days, respectively with no significant difference between the 150-mg treatment arm and placebo.Median changes in total HIV-1 DNA copies/106 PBMCs for ABX464 150-mg, 50-mg and placebo arms after 28 days of treatment were −40 (range −434 to +194), −115 (range −116 to −114) and 25 (range −35 to +218), respectively, showing a decrease in the intervention arms. There were 6/14, 2/2, and 0/4 responders for ABX464 150 mg, 50 mg and placebo, respectively. No significant difference was seen between treatment arms and placebo with respect to these virological parameters. Conclusions: This small controlled study confirmed the good safety and tolerability of ABX464 and provides some evidence of a potential reduction of the HIV-1 reservoir in terms of HIV-1 DNA levels in PBMCs when it was added to an HIV-1 protease inhibitor-based regimen. These results will need to be confirmed in a larger study. ABX464, safety, tolerability, HIV-1, Phase IIa study, HIV-1 reservoirs, viral rebound Microbiology Public aspects of medicine Jean-Marc Steens verfasserin aut Paul Gineste verfasserin aut Basiel Cole verfasserin aut Sam Kint verfasserin aut P. Noel Barrett verfasserin aut Jamal Tazi verfasserin aut Didier Scherrer verfasserin aut Hartmut J. Ehrlich verfasserin aut Linos Vandekerckhove verfasserin aut In Journal of Virus Eradication Elsevier, 2021 5(2019), 1, Seite 10-22 (DE-627)867995882 (DE-600)2868549-0 20556659 nnns volume:5 year:2019 number:1 pages:10-22 https://doi.org/10.1016/S2055-6640(20)30273-9 kostenfrei https://doaj.org/article/3ef3f0db63364cc288365e8f7330998c kostenfrei http://www.sciencedirect.com/science/article/pii/S2055664020302739 kostenfrei https://doaj.org/toc/2055-6640 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 5 2019 1 10-22 |
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10.1016/S2055-6640(20)30273-9 doi (DE-627)DOAJ058998829 (DE-599)DOAJ3ef3f0db63364cc288365e8f7330998c DE-627 ger DE-627 rakwb eng QR1-502 RA1-1270 Sofie Rutsaert verfasserin aut Safety, tolerability and impact on viral reservoirs of the addition to antiretroviral therapy of ABX464, an investigational antiviral drug, in individuals living with HIV-1: a Phase IIa randomised controlled study 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Objectives: To assess the safety and tolerability as well as antiretroviral impact of ABX464, an oral investigational drug with a novel mechanism of HIV-1 inhibition (ClinicalTrials.gov NCT02735863). Methods: Randomised, double-blind, placebo-controlled, Phase IIa study in individuals living with HIV-1 on antiretroviral therapy at six clinical centres in Spain, France and Belgium. ABX464 was administered once a day to 22 fully controlled HIV-1-positive participants at two doses (50 mg, n=6 and 150 mg, n=16) versus placebo, which was given to eight participants for 28 days in combination with a boosted protease inhibitor (darunavir/ritonavir or darunavir/cobicistat). The primary objective of the study was to assess ABX464 safety and tolerability when used in combination with darunavir boosted therapy. The secondary objective was to study antiretroviral efficacy on viral reservoirs using time to viral rebound following treatment interruption. The impact of ABX464 on HIV-1 reservoirs was further assessed by measuring levels of total HIV-1 in peripheral blood mononuclear cells (PBMCs) in the intervention arm versus placebo. A positive response was defined as an absolute reduction in HIV-1 DNA of at least 50 copies/106 PBMCs and a relative decrease <25% of HIV-1 DNA level. Results: Twenty-six of the 30 randomly allocated participants completed the study according to the study protocol. ABX464 was found to be safe and well tolerated with the majority of adverse events (AEs) being mild or moderate. Of the participants, 22 (73.3%) experienced treatment-associated AEs (93.8%, 66.7%, 37.5% in the ABX464 150-mg, 50-mg dose and placebo arms, respectively). Percentages for combined grade 3/4 AEs for the three arms were 6.3%, 0% and 12.5%, respectively.Median time (Kaplan–Meier estimates) to viral rebound for ABX464 150-mg, 50-mg and placebo arms were 12.0 (95% confidence interval [CI]: 10–15), 15.5 (95% CI 14–22) and 15.5 (95% CI 1–22) days, respectively with no significant difference between the 150-mg treatment arm and placebo.Median changes in total HIV-1 DNA copies/106 PBMCs for ABX464 150-mg, 50-mg and placebo arms after 28 days of treatment were −40 (range −434 to +194), −115 (range −116 to −114) and 25 (range −35 to +218), respectively, showing a decrease in the intervention arms. There were 6/14, 2/2, and 0/4 responders for ABX464 150 mg, 50 mg and placebo, respectively. No significant difference was seen between treatment arms and placebo with respect to these virological parameters. Conclusions: This small controlled study confirmed the good safety and tolerability of ABX464 and provides some evidence of a potential reduction of the HIV-1 reservoir in terms of HIV-1 DNA levels in PBMCs when it was added to an HIV-1 protease inhibitor-based regimen. These results will need to be confirmed in a larger study. ABX464, safety, tolerability, HIV-1, Phase IIa study, HIV-1 reservoirs, viral rebound Microbiology Public aspects of medicine Jean-Marc Steens verfasserin aut Paul Gineste verfasserin aut Basiel Cole verfasserin aut Sam Kint verfasserin aut P. Noel Barrett verfasserin aut Jamal Tazi verfasserin aut Didier Scherrer verfasserin aut Hartmut J. Ehrlich verfasserin aut Linos Vandekerckhove verfasserin aut In Journal of Virus Eradication Elsevier, 2021 5(2019), 1, Seite 10-22 (DE-627)867995882 (DE-600)2868549-0 20556659 nnns volume:5 year:2019 number:1 pages:10-22 https://doi.org/10.1016/S2055-6640(20)30273-9 kostenfrei https://doaj.org/article/3ef3f0db63364cc288365e8f7330998c kostenfrei http://www.sciencedirect.com/science/article/pii/S2055664020302739 kostenfrei https://doaj.org/toc/2055-6640 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 5 2019 1 10-22 |
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10.1016/S2055-6640(20)30273-9 doi (DE-627)DOAJ058998829 (DE-599)DOAJ3ef3f0db63364cc288365e8f7330998c DE-627 ger DE-627 rakwb eng QR1-502 RA1-1270 Sofie Rutsaert verfasserin aut Safety, tolerability and impact on viral reservoirs of the addition to antiretroviral therapy of ABX464, an investigational antiviral drug, in individuals living with HIV-1: a Phase IIa randomised controlled study 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Objectives: To assess the safety and tolerability as well as antiretroviral impact of ABX464, an oral investigational drug with a novel mechanism of HIV-1 inhibition (ClinicalTrials.gov NCT02735863). Methods: Randomised, double-blind, placebo-controlled, Phase IIa study in individuals living with HIV-1 on antiretroviral therapy at six clinical centres in Spain, France and Belgium. ABX464 was administered once a day to 22 fully controlled HIV-1-positive participants at two doses (50 mg, n=6 and 150 mg, n=16) versus placebo, which was given to eight participants for 28 days in combination with a boosted protease inhibitor (darunavir/ritonavir or darunavir/cobicistat). The primary objective of the study was to assess ABX464 safety and tolerability when used in combination with darunavir boosted therapy. The secondary objective was to study antiretroviral efficacy on viral reservoirs using time to viral rebound following treatment interruption. The impact of ABX464 on HIV-1 reservoirs was further assessed by measuring levels of total HIV-1 in peripheral blood mononuclear cells (PBMCs) in the intervention arm versus placebo. A positive response was defined as an absolute reduction in HIV-1 DNA of at least 50 copies/106 PBMCs and a relative decrease <25% of HIV-1 DNA level. Results: Twenty-six of the 30 randomly allocated participants completed the study according to the study protocol. ABX464 was found to be safe and well tolerated with the majority of adverse events (AEs) being mild or moderate. Of the participants, 22 (73.3%) experienced treatment-associated AEs (93.8%, 66.7%, 37.5% in the ABX464 150-mg, 50-mg dose and placebo arms, respectively). Percentages for combined grade 3/4 AEs for the three arms were 6.3%, 0% and 12.5%, respectively.Median time (Kaplan–Meier estimates) to viral rebound for ABX464 150-mg, 50-mg and placebo arms were 12.0 (95% confidence interval [CI]: 10–15), 15.5 (95% CI 14–22) and 15.5 (95% CI 1–22) days, respectively with no significant difference between the 150-mg treatment arm and placebo.Median changes in total HIV-1 DNA copies/106 PBMCs for ABX464 150-mg, 50-mg and placebo arms after 28 days of treatment were −40 (range −434 to +194), −115 (range −116 to −114) and 25 (range −35 to +218), respectively, showing a decrease in the intervention arms. There were 6/14, 2/2, and 0/4 responders for ABX464 150 mg, 50 mg and placebo, respectively. No significant difference was seen between treatment arms and placebo with respect to these virological parameters. Conclusions: This small controlled study confirmed the good safety and tolerability of ABX464 and provides some evidence of a potential reduction of the HIV-1 reservoir in terms of HIV-1 DNA levels in PBMCs when it was added to an HIV-1 protease inhibitor-based regimen. These results will need to be confirmed in a larger study. ABX464, safety, tolerability, HIV-1, Phase IIa study, HIV-1 reservoirs, viral rebound Microbiology Public aspects of medicine Jean-Marc Steens verfasserin aut Paul Gineste verfasserin aut Basiel Cole verfasserin aut Sam Kint verfasserin aut P. Noel Barrett verfasserin aut Jamal Tazi verfasserin aut Didier Scherrer verfasserin aut Hartmut J. Ehrlich verfasserin aut Linos Vandekerckhove verfasserin aut In Journal of Virus Eradication Elsevier, 2021 5(2019), 1, Seite 10-22 (DE-627)867995882 (DE-600)2868549-0 20556659 nnns volume:5 year:2019 number:1 pages:10-22 https://doi.org/10.1016/S2055-6640(20)30273-9 kostenfrei https://doaj.org/article/3ef3f0db63364cc288365e8f7330998c kostenfrei http://www.sciencedirect.com/science/article/pii/S2055664020302739 kostenfrei https://doaj.org/toc/2055-6640 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 5 2019 1 10-22 |
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Sofie Rutsaert @@aut@@ Jean-Marc Steens @@aut@@ Paul Gineste @@aut@@ Basiel Cole @@aut@@ Sam Kint @@aut@@ P. Noel Barrett @@aut@@ Jamal Tazi @@aut@@ Didier Scherrer @@aut@@ Hartmut J. Ehrlich @@aut@@ Linos Vandekerckhove @@aut@@ |
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Methods: Randomised, double-blind, placebo-controlled, Phase IIa study in individuals living with HIV-1 on antiretroviral therapy at six clinical centres in Spain, France and Belgium. ABX464 was administered once a day to 22 fully controlled HIV-1-positive participants at two doses (50 mg, n=6 and 150 mg, n=16) versus placebo, which was given to eight participants for 28 days in combination with a boosted protease inhibitor (darunavir/ritonavir or darunavir/cobicistat). The primary objective of the study was to assess ABX464 safety and tolerability when used in combination with darunavir boosted therapy. The secondary objective was to study antiretroviral efficacy on viral reservoirs using time to viral rebound following treatment interruption. The impact of ABX464 on HIV-1 reservoirs was further assessed by measuring levels of total HIV-1 in peripheral blood mononuclear cells (PBMCs) in the intervention arm versus placebo. A positive response was defined as an absolute reduction in HIV-1 DNA of at least 50 copies/106 PBMCs and a relative decrease <25% of HIV-1 DNA level. Results: Twenty-six of the 30 randomly allocated participants completed the study according to the study protocol. ABX464 was found to be safe and well tolerated with the majority of adverse events (AEs) being mild or moderate. Of the participants, 22 (73.3%) experienced treatment-associated AEs (93.8%, 66.7%, 37.5% in the ABX464 150-mg, 50-mg dose and placebo arms, respectively). Percentages for combined grade 3/4 AEs for the three arms were 6.3%, 0% and 12.5%, respectively.Median time (Kaplan–Meier estimates) to viral rebound for ABX464 150-mg, 50-mg and placebo arms were 12.0 (95% confidence interval [CI]: 10–15), 15.5 (95% CI 14–22) and 15.5 (95% CI 1–22) days, respectively with no significant difference between the 150-mg treatment arm and placebo.Median changes in total HIV-1 DNA copies/106 PBMCs for ABX464 150-mg, 50-mg and placebo arms after 28 days of treatment were −40 (range −434 to +194), −115 (range −116 to −114) and 25 (range −35 to +218), respectively, showing a decrease in the intervention arms. There were 6/14, 2/2, and 0/4 responders for ABX464 150 mg, 50 mg and placebo, respectively. No significant difference was seen between treatment arms and placebo with respect to these virological parameters. Conclusions: This small controlled study confirmed the good safety and tolerability of ABX464 and provides some evidence of a potential reduction of the HIV-1 reservoir in terms of HIV-1 DNA levels in PBMCs when it was added to an HIV-1 protease inhibitor-based regimen. 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QR1-502 RA1-1270 Safety, tolerability and impact on viral reservoirs of the addition to antiretroviral therapy of ABX464, an investigational antiviral drug, in individuals living with HIV-1: a Phase IIa randomised controlled study ABX464, safety, tolerability, HIV-1, Phase IIa study, HIV-1 reservoirs, viral rebound |
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Safety, tolerability and impact on viral reservoirs of the addition to antiretroviral therapy of ABX464, an investigational antiviral drug, in individuals living with HIV-1: a Phase IIa randomised controlled study |
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safety, tolerability and impact on viral reservoirs of the addition to antiretroviral therapy of abx464, an investigational antiviral drug, in individuals living with hiv-1: a phase iia randomised controlled study |
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Safety, tolerability and impact on viral reservoirs of the addition to antiretroviral therapy of ABX464, an investigational antiviral drug, in individuals living with HIV-1: a Phase IIa randomised controlled study |
| abstract |
Objectives: To assess the safety and tolerability as well as antiretroviral impact of ABX464, an oral investigational drug with a novel mechanism of HIV-1 inhibition (ClinicalTrials.gov NCT02735863). Methods: Randomised, double-blind, placebo-controlled, Phase IIa study in individuals living with HIV-1 on antiretroviral therapy at six clinical centres in Spain, France and Belgium. ABX464 was administered once a day to 22 fully controlled HIV-1-positive participants at two doses (50 mg, n=6 and 150 mg, n=16) versus placebo, which was given to eight participants for 28 days in combination with a boosted protease inhibitor (darunavir/ritonavir or darunavir/cobicistat). The primary objective of the study was to assess ABX464 safety and tolerability when used in combination with darunavir boosted therapy. The secondary objective was to study antiretroviral efficacy on viral reservoirs using time to viral rebound following treatment interruption. The impact of ABX464 on HIV-1 reservoirs was further assessed by measuring levels of total HIV-1 in peripheral blood mononuclear cells (PBMCs) in the intervention arm versus placebo. A positive response was defined as an absolute reduction in HIV-1 DNA of at least 50 copies/106 PBMCs and a relative decrease <25% of HIV-1 DNA level. Results: Twenty-six of the 30 randomly allocated participants completed the study according to the study protocol. ABX464 was found to be safe and well tolerated with the majority of adverse events (AEs) being mild or moderate. Of the participants, 22 (73.3%) experienced treatment-associated AEs (93.8%, 66.7%, 37.5% in the ABX464 150-mg, 50-mg dose and placebo arms, respectively). Percentages for combined grade 3/4 AEs for the three arms were 6.3%, 0% and 12.5%, respectively.Median time (Kaplan–Meier estimates) to viral rebound for ABX464 150-mg, 50-mg and placebo arms were 12.0 (95% confidence interval [CI]: 10–15), 15.5 (95% CI 14–22) and 15.5 (95% CI 1–22) days, respectively with no significant difference between the 150-mg treatment arm and placebo.Median changes in total HIV-1 DNA copies/106 PBMCs for ABX464 150-mg, 50-mg and placebo arms after 28 days of treatment were −40 (range −434 to +194), −115 (range −116 to −114) and 25 (range −35 to +218), respectively, showing a decrease in the intervention arms. There were 6/14, 2/2, and 0/4 responders for ABX464 150 mg, 50 mg and placebo, respectively. No significant difference was seen between treatment arms and placebo with respect to these virological parameters. Conclusions: This small controlled study confirmed the good safety and tolerability of ABX464 and provides some evidence of a potential reduction of the HIV-1 reservoir in terms of HIV-1 DNA levels in PBMCs when it was added to an HIV-1 protease inhibitor-based regimen. These results will need to be confirmed in a larger study. |
| abstractGer |
Objectives: To assess the safety and tolerability as well as antiretroviral impact of ABX464, an oral investigational drug with a novel mechanism of HIV-1 inhibition (ClinicalTrials.gov NCT02735863). Methods: Randomised, double-blind, placebo-controlled, Phase IIa study in individuals living with HIV-1 on antiretroviral therapy at six clinical centres in Spain, France and Belgium. ABX464 was administered once a day to 22 fully controlled HIV-1-positive participants at two doses (50 mg, n=6 and 150 mg, n=16) versus placebo, which was given to eight participants for 28 days in combination with a boosted protease inhibitor (darunavir/ritonavir or darunavir/cobicistat). The primary objective of the study was to assess ABX464 safety and tolerability when used in combination with darunavir boosted therapy. The secondary objective was to study antiretroviral efficacy on viral reservoirs using time to viral rebound following treatment interruption. The impact of ABX464 on HIV-1 reservoirs was further assessed by measuring levels of total HIV-1 in peripheral blood mononuclear cells (PBMCs) in the intervention arm versus placebo. A positive response was defined as an absolute reduction in HIV-1 DNA of at least 50 copies/106 PBMCs and a relative decrease <25% of HIV-1 DNA level. Results: Twenty-six of the 30 randomly allocated participants completed the study according to the study protocol. ABX464 was found to be safe and well tolerated with the majority of adverse events (AEs) being mild or moderate. Of the participants, 22 (73.3%) experienced treatment-associated AEs (93.8%, 66.7%, 37.5% in the ABX464 150-mg, 50-mg dose and placebo arms, respectively). Percentages for combined grade 3/4 AEs for the three arms were 6.3%, 0% and 12.5%, respectively.Median time (Kaplan–Meier estimates) to viral rebound for ABX464 150-mg, 50-mg and placebo arms were 12.0 (95% confidence interval [CI]: 10–15), 15.5 (95% CI 14–22) and 15.5 (95% CI 1–22) days, respectively with no significant difference between the 150-mg treatment arm and placebo.Median changes in total HIV-1 DNA copies/106 PBMCs for ABX464 150-mg, 50-mg and placebo arms after 28 days of treatment were −40 (range −434 to +194), −115 (range −116 to −114) and 25 (range −35 to +218), respectively, showing a decrease in the intervention arms. There were 6/14, 2/2, and 0/4 responders for ABX464 150 mg, 50 mg and placebo, respectively. No significant difference was seen between treatment arms and placebo with respect to these virological parameters. Conclusions: This small controlled study confirmed the good safety and tolerability of ABX464 and provides some evidence of a potential reduction of the HIV-1 reservoir in terms of HIV-1 DNA levels in PBMCs when it was added to an HIV-1 protease inhibitor-based regimen. These results will need to be confirmed in a larger study. |
| abstract_unstemmed |
Objectives: To assess the safety and tolerability as well as antiretroviral impact of ABX464, an oral investigational drug with a novel mechanism of HIV-1 inhibition (ClinicalTrials.gov NCT02735863). Methods: Randomised, double-blind, placebo-controlled, Phase IIa study in individuals living with HIV-1 on antiretroviral therapy at six clinical centres in Spain, France and Belgium. ABX464 was administered once a day to 22 fully controlled HIV-1-positive participants at two doses (50 mg, n=6 and 150 mg, n=16) versus placebo, which was given to eight participants for 28 days in combination with a boosted protease inhibitor (darunavir/ritonavir or darunavir/cobicistat). The primary objective of the study was to assess ABX464 safety and tolerability when used in combination with darunavir boosted therapy. The secondary objective was to study antiretroviral efficacy on viral reservoirs using time to viral rebound following treatment interruption. The impact of ABX464 on HIV-1 reservoirs was further assessed by measuring levels of total HIV-1 in peripheral blood mononuclear cells (PBMCs) in the intervention arm versus placebo. A positive response was defined as an absolute reduction in HIV-1 DNA of at least 50 copies/106 PBMCs and a relative decrease <25% of HIV-1 DNA level. Results: Twenty-six of the 30 randomly allocated participants completed the study according to the study protocol. ABX464 was found to be safe and well tolerated with the majority of adverse events (AEs) being mild or moderate. Of the participants, 22 (73.3%) experienced treatment-associated AEs (93.8%, 66.7%, 37.5% in the ABX464 150-mg, 50-mg dose and placebo arms, respectively). Percentages for combined grade 3/4 AEs for the three arms were 6.3%, 0% and 12.5%, respectively.Median time (Kaplan–Meier estimates) to viral rebound for ABX464 150-mg, 50-mg and placebo arms were 12.0 (95% confidence interval [CI]: 10–15), 15.5 (95% CI 14–22) and 15.5 (95% CI 1–22) days, respectively with no significant difference between the 150-mg treatment arm and placebo.Median changes in total HIV-1 DNA copies/106 PBMCs for ABX464 150-mg, 50-mg and placebo arms after 28 days of treatment were −40 (range −434 to +194), −115 (range −116 to −114) and 25 (range −35 to +218), respectively, showing a decrease in the intervention arms. There were 6/14, 2/2, and 0/4 responders for ABX464 150 mg, 50 mg and placebo, respectively. No significant difference was seen between treatment arms and placebo with respect to these virological parameters. Conclusions: This small controlled study confirmed the good safety and tolerability of ABX464 and provides some evidence of a potential reduction of the HIV-1 reservoir in terms of HIV-1 DNA levels in PBMCs when it was added to an HIV-1 protease inhibitor-based regimen. These results will need to be confirmed in a larger study. |
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Safety, tolerability and impact on viral reservoirs of the addition to antiretroviral therapy of ABX464, an investigational antiviral drug, in individuals living with HIV-1: a Phase IIa randomised controlled study |
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https://doi.org/10.1016/S2055-6640(20)30273-9 https://doaj.org/article/3ef3f0db63364cc288365e8f7330998c http://www.sciencedirect.com/science/article/pii/S2055664020302739 https://doaj.org/toc/2055-6640 |
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Jean-Marc Steens Paul Gineste Basiel Cole Sam Kint P. Noel Barrett Jamal Tazi Didier Scherrer Hartmut J. Ehrlich Linos Vandekerckhove |
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Jean-Marc Steens Paul Gineste Basiel Cole Sam Kint P. Noel Barrett Jamal Tazi Didier Scherrer Hartmut J. Ehrlich Linos Vandekerckhove |
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10.1016/S2055-6640(20)30273-9 |
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2024-07-03T21:14:24.730Z |
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