Delving into the Latest Updates on Darunavir Ethanolate/Ritonavir with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

DARUNAVIR AND RITONAVIR, Darunavir/ritonavir, Virontar

+ [1]

Target

HIV-1 pol

Mechanism

HIV-1 pol inhibitors(Human immunodeficiency virus type 1 protease inhibitors)

Therapeutic Areas

Immune System DiseasesInfectious DiseasesUrogenital Diseases

Active Indication

HIV Infections

Inactive Indication-

Originator Organization

Laboratorios Richmond SACIF

Active Organization

Laboratorios Richmond SACIFMylan Pharmaceuticals, Inc.

Inactive Organization-

Drug Highest PhaseApproved

First Approval Date

AR (01 Jan 2015),

HIV Infections

Regulation-

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Structure

Molecular FormulaC29H43N3O8S

InChIKeyQWSHKNICRJHQCY-VBTXLZOXSA-N

CAS Registry635728-49-3

View All Structures (2)

AbstractBackgroundRitonavir‐boosted darunavir (DRV/r) is a preferred protease inhibitor in pregnant women living with HIV. Current practice at British Columbia's referral centre (the Oak Tree Clinic) is to dose DRV/r as 800/100 mg daily throughout pregnancy, although some guidelines recommend DRV/r 600/100 mg twice daily due to altered pharmacokinetics with once‐daily dosing.ObjectivesWe describe the effect of once‐daily DRV/r on viral suppression, vertical transmission, adverse drug effects and adherence in pregnant women living with HIV.MethodsThis was a retrospective analysis of pregnant women living with HIV in British Columbia. Eligible women gave birth between January 2015 and August 2021, and took DRV/r 800/100 mg daily at any time during pregnancy.ResultsThirty‐four women were included in this study. The mean (SD) age was 33 (5) years. Thirty (88%) women were diagnosed with HIV prior to pregnancy, with 22 (73%) having viral suppression at baseline. Four (12%) were diagnosed in pregnancy, with a median baseline viral load of 9616 copies/mL (range 8370–165 000). Viral suppression was achieved by 16 (100%), 24 (75%) and 26 (74%) women in the first, second and third trimesters, respectively. No vertical transmission occurred. This combination was well tolerated, with adverse drug effects that did not result in discontinuation or change in therapy. Most women maintained >75% adherence to once‐daily DRV/r at all times during pregnancy.ConclusionsRitonavir‐boosted darunavir 800/100 mg daily appears to be an appropriate dosing strategy for pregnant women living with HIV who are able to maintain optimal adherence.

01 Jun 2023·eClinicalMedicine

Nucleoside/nucleotide reverse transcriptase inhibitor sparing regimen with once daily integrase inhibitor plus boosted darunavir is non-inferior to standard of care in virologically-suppressed children and adolescents living with HIV – Week 48 results of the randomised SMILE Penta-17-ANRS 152 clinical trial

Article

Author: Elenga, N. ; Gibb, Diana M. ; Tuna, J. ; Little, E. ; Ford, Deborah ; Blackstone, J. ; Fortuny Guasch, C. ; Van-Looy, N. ; Fernández, M. ; Puangmalai, P. ; Saidi, Y. ; Thapwai, T. ; Wachinger, T. ; Maduna, N. ; Silva Milhiero, T. ; Teixeira, C. ; Hirt, D. ; Doshi, S. ; Khusuwan, S. ; Khamjakkaew, W. ; Namuddu, R. ; Kiyimba, L. ; Sripaoraya, W. ; Paioni, Paolo ; Sampaio, A.C. ; Lawrence, L. ; Cotton, Mark ; Kyobutungi, P. ; Amuge, Pauline ; Slade, G. ; Pongprapass, S. ; Morkunaite, G. ; Prieto Tato, L. ; Turkova, A. ; Thewsoongnoen, J. ; Ford, D. ; Kalhert, C. ; Harper, L. ; Mbabazi, R. ; Saenjum, C. ; Babiker, Abdel ; Musiime, V. ; Srirompotong, U. ; Pouchain, H. ; Bbuye, D. ; Mendes, A.C. ; Ngampiyaskul, C. ; Khunene, M. ; Uyungrwoth, A. ; Dell’Orso, M. ; Maseko, L. ; Ferraz, I. ; Sibanda, N. ; Soria, A. ; Basiimwa, R. ; Lakha, R. ; Coto, M. ; Kaudha, E. ; Kekitiinwa, A.R. ; Niehues, T. ; Riault, Y. ; Fernandes, A. ; Nannungi, M. ; Liberty, Afaaf A. ; Townsend, S. ; Pavia Ruz, Noris ; Junkaew, R. ; Primak, N. ; Mespoulhe, P. ; Babu, E.L. ; Than-in-at, K. ; Tching Sin, M. ; Nascimento, H. ; Plonné, D. ; Ramos Amador, J.T. ; Navarro Gómez, M. ; Bilardi, D. ; Bologna, R. ; Ruklao, C. ; Barnabas, S. ; Morén, C. ; Gandhi, K. ; Vicentini, E. ; Wessels, M. ; Donngernl, D. ; Chan, Man K. ; Arulananthan, A. ; Agaba, G. ; Singh, U. ; Saegesser, C. ; Coelho, A. ; Raus, I. ; Pavia-Ruz, N. ; Vaughn-Gordon, Y. ; Nabwire, I. ; Muñoz Fernández, M.A. ; Manyi, F. ; Mulindwa, A. ; Chereau, N. ; Pinheiro, H. ; Namanda, S. ; Sukrakanchana, P. ; Neri-Macias, A. ; Groenewald, M. ; Saïdi, Yacine ; Moragas, M. ; Kitabalwa, J. ; Kamkoonmongkol, A. ; Nakabuye, S. ; Hamlyn, E. ; Torres Arauz, M. ; Cubells, M. ; Mostovenko, O. ; Nabalamba, M. ; Mur, A. ; Adebayo, A. ; Candeias, M.F. ; Nduna, N. ; Cagnot, C. ; Ategeka, J. ; Akoojee, N. ; Thungkham, K. ; Jourdain, G. ; Chalermpantmetagul, Suwalai ; Kekitiinwa, Adeodata R. ; Fedullo, A.G. ; Mulima, D. ; Weldon, S. ; Fourie, Y. ; Nalubwama, J. ; Welch, Steven B. ; Ahimbisibwe, G. ; Khamkon, J. ; Chinwong, D. ; Smuts, M. ; Groenewald, Marisa ; Torrent, R. ; Daniel, T. ; Petpranee, T. ; Inyakuwal, C. ; Ganger, L. ; Bologna, Rosa ; Giaquinto, C. ; Kanjanavanit, S. ; Taicz, M. ; Faria, C. ; Vergnano, S. ; Cardão, M. ; Theunissen, M. ; Musiime, Victor ; Tumusiime, J. ; Monteiro, F. ; Meeboon, C. ; Marques, Laura ; Epalza, C. ; Mangano, A. ; Daglish, J. ; Nardone, A. ; Léger, L. ; Gilmour, C. ; Hoorn, L. ; Mann, B. ; Flet, L. ; Hafner, S. ; Nsibuka Kisekka, M. ; Niehues, Tim ; Augustin, S. ; Ngo Giang Huong, N. ; Rojo Conejo, P. ; Compagnucci, A. ; Mendes, D. ; Krueduangkam, N. ; Chamjamrat, W. ; Gao, L. ; Picault, L. ; Musiime, A. ; Srirojana, S. ; Prieto Tato, Luis ; Pieterse, S. ; Mamiane, A. ; Nambi, E. ; Kadhuba, R. ; Calvert, J. ; Baliruno, D. ; Reis Melo, A. ; Srisuk, W. ; Inshaw, J. ; Espinosa-Sotero, C. ; Isaacs, M. ; Williams, E.D. ; Ball, C. ; Oliveira, A. ; Phunkhum, P. ; Govender, S. ; Mwebaza, J. ; Meyer, L. ; Bhana, P. ; Rutebarika, D. ; Nalugo, A. ; Denjanta, S. ; Ribeiro, R. ; Tearsansern, P. ; Kongponoi, A. ; Matos, A.C. ; Liberty, A. ; Guillén Martin, S. ; Namusanje, J. ; Tikabibamu, J. ; Nolan, Aoife ; Boni, J. ; Kamboua, P. ; Blaise, N. ; Nyati, M. ; Rubanga, E. ; Nayagam, D. ; Widuch, K. ; Cotton, M. ; Hawkins, S. ; Nunes, R. ; Nabukeera Barung, N. ; Dollenmaier, G. ; Baita, A. ; Garcia, I. ; Gatto, M. ; Wohlwend, B. ; Gomes Neves, E. ; Estepa, C. ; Vadee, A. ; Ramos Amador, Jose Tomas ; Prucha, C. ; Coelho, Alexandra ; Reliquet, Véronique ; Mugarura, L. ; Cressey, T.R. ; Stepchenkova, T. ; Chalermpantmetagul, S. ; Compagnucci, Alexandra ; Sans, E. ; Ojok, M. ; Nolan, A. ; Sainz Costa, T. ; Giaquinto, Carlo ; Yingyong, P. ; Nazzinda, R. ; Violari, Avy ; Na Kalasin, N. ; Kaewbundit, A. ; Terrine, M.D. ; Volokha, A. ; Kaewmamueng, K. ; Kruenual, N. ; Corte-Real, R. ; Gibb, D.M. ; Noguera Julian, T. ; Amuge, P. ; Jarillo-Quijada, M.D. ; Limplertjareanwanich, J. ; Kaudha, Elizabeth ; Mellado Peña, M.J. ; Padrao, A. ; Caldeira, A. ; Chan, M. ; Coetzee, J. ; Duppenthaler, A. ; Tavares, M. ; Prieto, L. ; Ndiaye, M. ; Essack, Z. ; Noguera, T. ; Namuli, F. ; Kanjanavanit, Suparat ; Paioni, P. ; Arazi, S. ; Greetanukroh, P. ; Labeja Ocitti, S.P. ; Kityo, C.M. ; Muñoz- Hernández, R. ; Kongsuk, K. ; Nsirim, E. ; Babiker, A. ; Thrasyvoulou, L. ; Chanto, N. ; Correira, C. ; Morkunaite, Gabija ; Erasmus, J. ; Nanduudu, A. ; Khamduang, W. ; Khannak, P. ; Ross, M. ; Escosa García, L. ; Nunn, A. ; Reliquet, V. ; Kenny, J. ; Gilmour-White, S. ; Hemon, C. ; Barbani, M. ; Laomanit, L. ; Tupper, K. ; Gomez Salcedo, P. ; Peongjakta, R. ; Murciano Cabeza, A. ; Mujyambere, E. ; Morgado, M. ; Kisitu, G.P. ; Cweya, A. ; Nakalyango, A. ; Nakandi, L. ; Sudsaard, P. ; Bruno, E. ; Irvine, E. ; Moreno, M. ; Cressey, Tim R. ; Scott, K. ; Bamford, A. ; Paredes, E. ; Marques, L. ; Hudson, F. ; Chutima, D. ; Chankun, T. ; Ramsagar, N. ; Circosta, S. ; Callaghan, A. ; Ounchanum, P. ; Mendez García, P. ; Simanic, S. ; Klinprung, S. ; Fry, S. ; Bamford, Alasdair ; Oruk, S. ; Fuller, E. ; Smith, K. ; Makola, C. ; Thaweesombat, Y. ; Odoch, D. ; Fabiane, S. ; Kouakam, C. ; Welch, S. ; Rodallec, A. ; Violari, A. ; Saewtrakool, C. ; Katemba, C. ; Bagirigomwa, E. ; Signorell, R. ; Riault, Yoann ; Mkhize, S. ; Ahmad, M. ; Kirabira, A. ; Castro, C. ; Volokha, Alla

BackgroundIntegrase inhibitor (INSTI) with boosted darunavir (DRV/r), a regimen with a high-resistance barrier, avoiding NRTI toxicities, might be a switching option in children living with HIV (CLWHIV).MethodsSMILE is a randomised non-inferiority trial evaluating safety and antiviral efficacy of once-daily INSTI + DRV/r vs. continuing on current standard-of-care (SOC) triple ART (2NRTI + boosted PI/NNRTI) in virologically-suppressed CLWHIV aged 6-18 years. The primary outcome is the proportion with confirmed HIV-RNA ≥50 copies/mL by week 48, estimated by Kaplan-Meier method. Non-inferiority margin was 10%. Registration number for SMILE are: ISRCTN11193709, NCT #: NCT02383108.FindingsBetween 10th June 2016 and 30th August 2019, 318 participants were enrolled from Africa 53%, Europe 24%, Thailand 15% and Latin America 8%, 158 INSTI + DRV/r [153 Dolutegravir (DTG); 5 Elvitegravir (EVG)], 160 SOC. Median (range) age was 14.7 years (7.6-18.0); CD4 count 782 cells/mm³ (227-1647); 61% female. Median follow-up was 64.3 weeks with no loss to follow-up. By 48 weeks, 8 INSTI + DRV/r vs. 12 SOC had confirmed HIV-RNA ≥50 copies/mL; difference (INSTI + DRV/r-SOC) -2.5% (95% CI: -7.6, 2.5%), showing non-inferiority. No major PI or INSTI resistance mutations were observed. There were no differences in safety between arms. By week 48, difference (INSTI + DRV/r-SOC) in mean CD4 count change from baseline was -48.3 cells/mm³ (95% CI: -93.4, -3.2; p = 0.036). Difference (INSTI + DRV/r-SOC) in mean HDL change from baseline was -4.1 mg/dL (95% CI: -6.7, -1.4; p = 0.003). Weight and Body Mass Index (BMI) increased more in INSTI + DRV/r than SOC [difference: 1.97 kg (95% CI: 1.1, 2.9; p < 0.001), 0.66 kg/m² (95% CI: 0.3, 1.0; p < 0.001)].InterpretationIn virologically-suppressed children, switching to INSTI + DRV/r was non-inferior virologically, with similar safety profile, to continuing SOC. Small but significant differences in CD4, HDL-cholesterol, weight and BMI were observed between INSTI + DRV/r vs. SOC although clinical relevance needs further investigation. SMILE data corroborate adult findings and provide evidence for this NRTI-sparing regimen for children and adolescents.FundingFondazione Penta Onlus, Gilead, Janssen, INSERM/ANRS and UK MRC. ViiV-Healthcare provided Dolutegravir.

09 Dec 2022·Medicine

Observational study to evaluate discontinuation of monotherapy with cobicistat-boosted darunavir in patients with human immunodeficiency virus

Article

Author: Montero, Marta ; Solana-Altabella, Antonio ; Salavert, Miguel ; Cuéllar-Monreal, Maria Jesús ; Monte-Boquet, Emilio ; Poveda-Andrés, José Luis ; Pérez-Huertas, Pablo

To evaluate the reasons for changing to monotherapy with protease inhibitors, together with the proportion and reasons for the interruption to treatment, in patients who have been treated at some point with cobicistat-boosted darunavir (DRV/c). Outpatients in a tertiary hospital. Observational retrospective study to evaluate monotherapy with DRV/c (800 mg/150 mg) in adult patients with human immunodeficiency virus infection, from December 2014 to July 2022. Demographic variables, viral load, cluster of differentiation 4 lymphocyte lymphocyte count, and antiretroviral therapy were assessed. 42 patients were included. 36% of the patients were undergoing monotherapy at the time of the analysis. The main reason for discontinuation was poor adherence. At time of analysis, 80% of the patients in monotherapy had an undetectable viral load. Antiretroviral therapy recommendations advise against exposing the patient to functional monotherapy with a single drug due to the high risk of virological failure and the onset of resistance to a single drug. Following the analysis of the results, DRV/c in monotherapy is not an effective strategy in the medium and long term due to factors such as lack of adherence or virological failure, although it can be maintained in specific circumstances. Therefore, patients undergoing monotherapy require close monitoring.

100 Deals associated with Darunavir Ethanolate/Ritonavir

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External Link

KEGG	Wiki	ATC	Drug Bank
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R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
HIV Infections	AR	Laboratorios Richmond SACIF	01 Jan 2015

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
HIV Infections	NDA/BLA	US	Mylan Pharmaceuticals, Inc.	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


SMILE PENTA-17 TRIAL (IAS2021)	Not Applicable	-	318	INSTI+Darunavir/r	(pqdcnfpucw): P-Value = 0.036 View more	-	01 Jan 2021
				boosted darunavir (Standard-of-care (SOC))
DRIVE-FORWARD, DRIVE-AHEAD (Pubmed \| Clin Infect Dis)	Phase 3	HIV Infections	-	Doravirine/lamivudine/tenofovir disoproxil fumarate	ntacjyobix(lhqrjksxil) = apggdlfptx zuhifzkivb (npdldwptqm ) View more	Positive	17 Mar 2020
				Darunavir plus ritonavir	ntacjyobix(lhqrjksxil) = zpykqcegxg zuhifzkivb (npdldwptqm ) View more
DRIVE-FORWARD (IAS2018)	Not Applicable	-	769	Doravirine (DOR)	(zbfbhxkgwt) = DOR 17.0%, DRV+r 23.8% awmdcvkgvf (eefwawzeah ) View more	Positive	01 Jan 2018
				Ritonavir-boosted darunavir (DRV+r)
NCT02770508 (ANDES, IAS2017)	Phase 4	HIV Infections	145	Darunavir/ritonavir plus lamivudine	(rluajlkmlt) = one patient was discontinued due to a drug-related grade 3 adverse event (rash) oqncjzmkpb (tbchhrxxgc ) View more	Positive	01 Jan 2017
				Triple therapy with DRV/RTV plus TDF/3TC
ANRS 12269 (IAS2017)	Not Applicable	HIV Infections Third line	201	Darunavir/r 600/100 mg BID + Raltegravir 400 mg BID	(tdnayxnztl) = kyaqgzasuc pvratzgips (colppjlavq ) View more	Positive	01 Jan 2017
NCT01516970 (PEPDar, CTgov)	Phase 3	HIV Infections	312	DRV/r+Ritonavir+Darunavir (Darunavir/Ritonavir Postexposure Prophylaxis (DRV/r PEP))	adjxvbjlps(wzgnzqbisb) = lqfldgpkkg jzcnztbmxf (ajgwqbicef, qwhyfuuloq - oxswnkehad) View more	-	11 Oct 2016
				SOCPEP (Standard of Care Postexposure Prophylaxis (SOCPEP))	adjxvbjlps(wzgnzqbisb) = tnsshvltty jzcnztbmxf (ajgwqbicef, qwqhgvulsp - yekifbzhot) View more
NCT01066962 (NEAT001/ANRS143, Pubmed \| Lancet HIV)	Phase 3	HIV Infections	146	Darunavir-ritonavir + Raltegravir	nqoervypxk(qpuiisjqtc) = tvrattaiya mrqwxfdxfv (elmsneblwy )	Positive	01 Nov 2015
				Darunavir-ritonavir + Tenofovir-emtricitabine	nqoervypxk(qpuiisjqtc) = hdndjakgdn mrqwxfdxfv (elmsneblwy )
Pubmed \| HIV Med	Not Applicable	-	-	etravirine plus darunavir/ritonavir	(ideuctngcp) = gwverwnnrk qtoxeisifd (fuvbxmrjoo ) View more	-	01 May 2015
				etravirine plus an alternative boosted protease inhibitor	(ideuctngcp) = zfjdehrgdc qtoxeisifd (fuvbxmrjoo ) View more
MODERN (IAS2015)	Not Applicable	-	-	Maraviroc (MVC) with darunavir/ritonavir (DRV/r)	(vfzijlswlv) = psxiffvpnm tkkriqwyic (uqqtpvbdvh, 243) View more	-	01 Jan 2015
				Tenofovir/emtricitabine (TDF/FTC) with DRV/r	(vfzijlswlv) = bpsmabpifv tkkriqwyic (uqqtpvbdvh, 288) View more
IAS2015	Not Applicable	Vitamin D Deficiency	70	Atripla	emydrcxabc(elqmwrwcif): P-Value = 0.03 View more	-	01 Jan 2015
				Darunavir/Ritonavir monotherapy (DRV/r)