An Open-label, Single-arm Study to Provide Continued Access to Study Drug to Participants Who Have Completed Pediatric Clinical Studies Involving Gilead HIV Treatments

The goal of this clinical study is to provide continued access to the study drug(s) to children and adolescents with human immunodeficiency virus type 1 (HIV-1) who completed their participation in an applicable parent study and to monitor for adverse events.
The primary objectives of this study are as follows:
To provide continued access to the study drug received in the parent protocol or switch to bictegravir/emtricitabine/tenofovir (B/F/TAF) for participants who completed a Gilead parent study evaluating drugs for HIV treatment.
To evaluate the safety of the study drug(s) in participants with HIV-1.

Start Date01 Sep 2024

Sponsor / Collaborator

Gilead Sciences, Inc.

NCT05334004 / RecruitingPhase 1IIT

A Phase I Study of Intra-anally Administered Lopinavir/Ritonavir in People Living With HIV (PLWH) With High-Grade Anal Intraepithelial Neoplasia (AIN 2/3)

This study is being done to assess the safety of lopinavir/ritonavir in patients with PLWH with AIN. 30 participants will be recruited and can expect to be on active study for approximately 3 months and long term follow up for 40 weeks.

Start Date19 Dec 2023

Sponsor / Collaborator

University of Wisconsin-Madison

CTR20221564 / CompletedNot Applicable

一项单中心、随机、开放、单剂量、四周期、完全重复交叉研究评价洛匹那韦利托那韦片在健康人群中的生物等效性

[Translation] A single-center, randomized, open-label, single-dose, four-period, completely repeated crossover study to evaluate the bioequivalence of lopinavir-ritonavir tablets in healthy subjects

主要研究目的：以印度Hetero Labs Limited生产的洛匹那韦利托那韦片作为受试制剂，AbbVie Inc生产的洛匹那韦利托那韦片[商品名：Kaletra®，每片含洛匹那韦200mg，利托那韦50mg]为参比制剂，评估两种制剂空腹和餐后给药的生物等效性。次要研究目的：评价印度Hetero Labs Limited生产的洛匹那韦利托那韦片单次口服给药的药代动力学（PK）特点。评价印度Hetero Labs Limited生产的洛匹那韦利托那韦片的安全性。

[Translation]

Primary study objective: To evaluate the bioequivalence of the two preparations when administered on an empty stomach and after a meal, using Lopinavir-Ritonavir Tablets produced by Hetero Labs Limited, India, as the test preparation and Lopinavir-Ritonavir Tablets produced by AbbVie Inc [trade name: Kaletra®, each tablet contains 200 mg of Lopinavir and 50 mg of Ritonavir] as the reference preparation. Secondary study objectives: To evaluate the pharmacokinetic (PK) characteristics of Lopinavir-Ritonavir Tablets produced by Hetero Labs Limited, India, after a single oral administration. To evaluate the safety of Lopinavir-Ritonavir Tablets produced by Hetero Labs Limited, India.

Start Date12 Jun 2022

Sponsor / Collaborator

Hainan Sihuan Pharmaceutical Co. Ltd.

100 Clinical Results associated with Lopinavir/Ritonavir

100 Translational Medicine associated with Lopinavir/Ritonavir

100 Patents (Medical) associated with Lopinavir/Ritonavir

1,261

Literatures (Medical) associated with Lopinavir/Ritonavir

01 Feb 2024·The Lancet. Global health

Clinical outcomes with second-line dolutegravir in people with virological failure on first-line non-nucleoside reverse transcriptase inhibitor-based regimens in South Africa: a retrospective cohort study

Article

Author: van Heerden, Rosemary ; Lessells, Richard J ; Asare, Kwabena ; Dorward, Jienchi ; van der Molen, Johan ; Lewis, Lara ; Sookrajh, Yukteshwar ; Khubone, Thokozani ; Garrett, Nigel ; Sosibo, Phelelani ; Naidoo, Kogieleum

BACKGROUND:

Dolutegravir (DTG) is recommended for second-line antiretroviral therapy (ART) after virological failure on first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens in people living with HIV in low-income and middle-income countries. We compared the effectiveness of DTG versus the previously recommended ritonavir-boosted lopinavir (LPV/r) regimen for second-line treatment in South Africa.

METHODS:

In this retrospective observational cohort study, we used routinely collected, de-identified data from 59 primary health-care facilities in eThekwini Municipality, KwaZulu-Natal, South Africa. We included people living with HIV aged 15 years or older with virological failure (defined as two consecutive viral loads of ≥1000 copies per mL at least 56 days apart) on first-line NNRTI-based ART containing tenofovir disoproxil fumarate (TDF) and who switched to second-line ART. Our primary outcomes were retention in care and viral suppression (<50 copies per mL) at 12 months after starting second-line treatment. We used modified Poisson regression models to compare these outcomes between second-line regimens (zidovudine [AZT]/emtricitabine or lamivudine [XTC]/DTG; TDF/XTC/DTG; and AZT/XTC/LPV/r).

FINDINGS:

We included 1214 participants in our study, of whom 729 (60%) were female and 485 (40%) were male, and whose median age was 36 years (IQR 30-42). 689 (57%) were switched to AZT/XTC/LPV/r, 217 (18%) to AZT/XTC/DTG, and 308 (25%) to TDF/XTC/DTG. Compared with AZT/XTC/LPV/r (75%), retention in care was higher with AZT/XTC/DTG (86%, adjusted risk ratio [aRR]=1·14, 95% CI 1·03-1·27; adjusted risk difference [aRD]=10·89%, 95% CI 2·01 to 19·78) but similar with TDF/XTC/DTG (77%, aRR=1·01, 0·94-1·10; aRD=1·04%, -5·03 to 7·12). Observed retention in care was lower with TDF/XTC/DTG than with AZT/XTC/DTG, although in multivariable analysis evidence for a difference was weak (aRR=0·89, 0·78-1·01, p=0·060; aRD=-9·85%, -20·33 to 0·63, p=0·066). Of 799 participants who were retained in care with a 12-month viral load test done, viral suppression was higher with AZT/XTC/DTG (59%; aRR=1·25, 1·06-1·47; aRD=11·57%, 2·37 to 20·76) and higher with TDF/XTC/DTG (61%; aRR=1·30, 1·14-1·48; aRD=14·16%, 7·14 to 21·18) than with AZT/XTC/LPV/r (47%).

INTERPRETATION:

These findings from routine care support further implementation of WHO's recommendation to use DTG instead of LPV/r in people living with HIV who experience virological failure while receiving first-line NNRTI-based ART.

FUNDING:

Bill & Melinda Gates Foundation.

TRANSLATION:

For the isiZulu translation of the abstract see Supplementary Materials section.

01 Jan 2024·Current research in structural biology

Inhibition of Plasmodium falciparum plasmepsins by drugs targeting HIV-1 protease: A way forward for antimalarial drug discovery

Article

Author: Rathore, Ishan ; Wlodawer, Alexander ; Mishra, Vandana ; Deshmukh, Anuradha ; Bhaumik, Prasenjit ; Yada, Rickey Y ; Patankar, Swati ; Chakraborty, Satadru ; Gustchina, Alla

Plasmodium species are causative agents of malaria, a disease that is a serious global health concern. FDA-approved HIV-1 protease inhibitors (HIV-1 PIs) have been reported to be effective in reducing the infection by Plasmodium parasites in the population co-infected with both HIV-1 and malaria. However, the mechanism of HIV-1 PIs in mitigating Plasmodium pathogenesis during malaria/HIV-1 co-infection is not fully understood. In this study we demonstrate that HIV-1 drugs ritonavir (RTV) and lopinavir (LPV) exhibit the highest inhibition activity against plasmepsin II (PMII) and plasmepsin X (PMX) of P. falciparum. Crystal structures of the complexes of PMII with both drugs have been determined. The inhibitors interact with PMII via multiple hydrogen bonding and hydrophobic interactions. The P4 moiety of RTV forms additional interactions compared to LPV and exhibits conformational flexibility in a large S4 pocket of PMII. Our study is also the first to report inhibition of P. falciparum PMX by RTV and the mode of binding of the drug to the PMX active site. Analysis of the crystal structures implies that PMs can accommodate bulkier groups of these inhibitors in their S4 binding pockets. Structurally similar active sites of different vacuolar and non-vacuolar PMs suggest the potential of HIV-1 PIs in targeting these enzymes with differential affinities. Our structural investigations and biochemical data emphasize PMs as crucial targets for repurposing HIV-1 PIs as antimalarial drugs.

20 Dec 2023·Chinese medical journal

Reasons, safety and efficacy analysis for conversion of HAART to TAF/FTC/BIC among HIV-infected patients

Article

Author: Ding, Yi ; Gao, Chengyu ; Gao, Guiju ; Yang, Di ; Zhao, Hongxin ; Li, Jialu ; Xu, Qiuhua ; Wu, Liang ; Liang, Hongyuan ; Ni, Liang ; Xiao, Jiang ; Wang, Fang ; Duan, Yujiao

Abstract:

Background::

This study aimed to determine the reasons for conversion and elucidate the safety and efficacy of transition to tenofovir alafenamide/emtricitabine/bictegravir sodium (TAF/FTC/BIC) in highly active antiretroviral therapy (HAART)-experienced HIV-infected patients in real-world settings.

Methods::

We conducted a retrospective cohort study. The treatment conversion rationales, safety, and effectiveness in 1684 HIV-infected patients with previous HAART experience who switched to TAF/FTC/BIC were evaluated at Beijing Ditan Hospital from September 2021 to Auguest 2022.

Results::

Regimen simplification (990/1684, 58.79%) was the most common reason for switching, followed by osteoporosis or osteopenia (375/1684, 22.27%), liver dysfunction (231/1684, 13.72%), decline in tenofovir alafenamide/emtricitabine/elvitegravir/cobicistat (TAF/FTC/EVG/c) with food restriction (215/1684, 12.77%), virological failure (116/1684, 6.89%), and renal dysfunction (90/1684, 5.34%). In patients receiving non-nucleotide reverse transcriptase inhibitors (NNRTI)-containing regimens, lipid panel changes 1 year after switching indicated a difference of 3.27 ± 1.10 mmol/L vs. 3.40 ± 1.59 mmol/L in triglyceride (P = 0.014), 4.82 ± 0.74 mmol/L vs. 4.88 ± 0.72 mmol/L in total cholesterol (P = 0.038), 3.09 ± 0.70 mmol/L vs. 3.18 ± 0.66 mmol/L in low-density lipoprotein (P <0.001), and 0.99 ± 0.11 mmol/L vs. 0.95 ± 0.10 mmol/L in high-density lipoprotein (P <0.001). Conversely, among patients receiving booster-containing regimens, including TAF/FTC/EVG/c and lopinavir/ritonavir (LPV/r), lipid panel changes presented decreased trends. We also observed an improved trend in viral load suppression, and alanine transaminase (ALT), aspartate transaminase (AST), estimated glomerular filtration rate (eGFR), and serum creatinine levels after the transition (P <0.001).

Conclusion::

The transition to TAF/FTC/BIC demonstrated good treatment potency. Furthermore, this study elucidates the motivations behind the adoption of TAF/FTC/BIC in real-world scenarios, providing clinical evidence supporting the stable conversion to TAF/FTC/BIC for HAART-experienced patients.

News (Medical) associated with Lopinavir/Ritonavir

01 Nov 2022

·endpts.com

Covid-19 continues to befuddle Big Pharma as AbbVie axes PhI of an oral drug

In the fight against Covid-19, AbbVie’s approved products and investigational assets have run into multiple hurdles. The latest is a Phase I axe, quietly revealed on the federal clinical trials database in recent days. The Chicago-area Big Pharma cited “re-evaluation of risk vs benefit (based on animal data)” in an update to the Phase I trial of ABBV-990. AbbVie had hoped the drug would work as a treatment for patients with SARS-CoV-2, but it appears it won’t make it past the 24-person healthy volunteer study conducted in northern Illinois. AbbVie did not reply to emailed requests for comment. It is unclear if the asset came from the Big Pharma’s partnership with Scripps Research’s Calibr, a drug discovery and development unit funded by the Bill & Melinda Gates Foundation. Endpoints News has reached out to Scripps, which announced the collaboration in March of this year. AbbVie has made multiple attempts to find antivirals and potential treatments to ward off the worst of the pandemic but hasn’t found the right one just yet. Multiple other biopharmas have attempted creating treatments and vaccines in the global fight against the pandemic, but many have run into hurdles, largely because of the various strains that have emerged along the way. For AbbVie specifically, the company had tried to bring forth an antibody combo — out of partner Harbour BioMed and researchers at Utrecht University and Erasmus Medical Center. But the asset doesn’t appear on AbbVie’s public pipeline after a Phase I wrapped up in 2021 . The antibody still shows up on Harbour’s website, with a “global license to AbbVie” description. The National Institute of Allergy and Infectious Diseases had also previously tried combining remdesivir with AbbVie’s Skyrizi , a human monoclonal antibody approved for plaque psoriasis. Earlier in the pandemic, AbbVie had also donated supplies of the HIV medicine Kaletra/Aluvia (lopinavir/ritonavir), but the WHO stopped the portion of a trial testing the treatment for hospitalized patients in July 2020.

AntibodyVaccineLicense out/inCollaborate

25 Oct 2022

·www.biospace.com

3T Biosciences Announces Appointment of John Leonard, M.D. to its Board of Directors

Current president and CEO of Intellia Therapeutics and previous global head of Abbvie's R&D brings more than 30 years' experience leading discovery, development, and launch of groundbreaking blockbuster medicines SAN FRANCISCO, Calif., Oct. 25, 2022 /PRNewswire/ -- 3T Biosciences ("3T"), an immunotherapy company changing the future of treatment for solid tumors and other immune-mediated diseases, today announced the appointment of John Leonard, M.D. to its board of directors. Dr. Leonard is currently president and chief executive officer (CEO) of Intellia Therapeutics ("Intellia"), which he joined in 2014 at its formation. He leads the company's efforts to turn its CRISPR-based genome editing technology into a therapeutic reality. Prior to Intellia, he served as chief scientific officer and global vice president of research and development (R&D) at AbbVie. "On behalf of the entire management team at 3T Biosciences, I am thrilled to welcome John to our board of directors," said Stefan J. Scherer, M.D., Ph.D., president and CEO of 3T Biosciences. "John has decades of experience leading breakthrough medicines through their discovery, development, and launch into blockbuster drugs. Because of his work, patients around the world now have better treatments for AIDS, autoimmune disorders, and many other life-altering diseases. His leadership will be an invaluable asset to 3T." "Working with promising novel therapeutic modalities is my passion, and 3T is truly transforming the way we look at treating solid tumors and immune-mediated diseases," said Dr. Leonard. "I believe in the company's mission and science, and I'm thrilled to join 3T's board of directors." Throughout his career, Dr. Leonard has overseen the development of numerous novel therapeutics at AbbVie and, prior to that, at Abbott, where he served as senior vice president of Global R&D. His groundbreaking work with HIV protease inhibitors NORVIR® (ritonavir) and KALETRA® (lopinavir/ritonavir) led to new treatment paradigms for AIDS and his years of work with HUMIRA® (adalimumab) made it the all-time top-selling drug worldwide. His contributions led to the significant growth of the R&D pipelines at Abbott and AbbVie. Dr. Leonard serves on the boards of Intellia and IQVIA. He received his M.D. from the Johns Hopkins University School of Medicine and completed his residency in internal medicine at Stanford University, followed by a fellowship at the National Institutes of Health. About 3T Biosciences 3T Biosciences is an immunotherapy company focused on discovering and developing next-generation therapies with curative potential based on its immune-response guided target discovery approach. 3T Biosciences' 3T-TRACE platform technology is designed to overcome the challenges of advancing T-cell receptor (TCR)-based therapeutics. Based in South San Francisco, 3T Biosciences is led by an experienced management team and supported by top investors including Westlake Village BioPartners, Lightspeed Venture Partners, and the Parker Institute for Cancer Immunotherapy. For more information, please visit .

Gene TherapyImmunotherapy

29 Nov 2012

·www.pharmatimes.com

Abbott chiefs OK AbbVie split, declare dividend

Abbott's Board of Directors has given the thumbs up for cleaving off its research arm, and has also declared a special dividend distributing the outstanding shares of the new firm's common stock. The company first announced in October 2011 that it would be spinning off its research-based pharmaceuticals business into a separate entity called AbbVie. Now, just a step away from completing the separation, Abbott's board has announced that for every one share of Abbott common shares held, shareholders will receive one share of AbbVie common stock. No fractional shares of AbbVie will be issued, with shareholders to receive cash for these instead, it said. The distribution of AbbVie common stock will finalise the split, establishing AbbVie as a research-based specialty biopharmaceuticals company with a broad portfolio of medicines. The newborn's chief asset will be the blockbuster Humira (adalimumab), followed by the prostate cancer drug Lupron (leuprolide), the HIV therapy Kaletra (lopinavir/ritonavir) and the hypothyroid medication Synthroid (levothyroxine). Abbott, on the other hand, will be one of the largest science-based healthcare companies with offerings in diagnostics, medical devices, nutritionals and branded generic pharmaceuticals – "all aligned with favourable healthcare trends", the firm noted.

100 Deals associated with Lopinavir/Ritonavir

External Link

KEGG	Wiki	ATC	Drug Bank
-	Lopinavir/Ritonavir	J05AR10	-

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
HIV Infections	US	AbbVie, Inc.	15 Sep 2000

Developing

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Coinfection	Phase 2	-	Abbott Laboratories	21 Jul 2005
Hepatitis C	Phase 2	-	Abbott Laboratories	21 Jul 2005

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04372628 (CTgov)	Phase 2	COVID-19	452	Lopinavir+Ritonavir (Group 2 - Lopinavir/Ritonavir)	khlxeltmsx(rywtnujxzk) = bchyydqwyc oizrjlkfve (ibwdnhdcyy, lqzwebonqb - dsrjhmdgew) View more	-	26 Jan 2023
				Placebo (Placebo Control Group)	khlxeltmsx(rywtnujxzk) = vyhyvqkaqq oizrjlkfve (ibwdnhdcyy, vcfxncihiz - nyattdtsbd) View more
NCT04372628 (Pubmed)	Phase 2	COVID-19	448	Lopinavir/ritonavir	gucwlvrvfk(hvvknbnhka) = xewpucecgv tmpocxnzbh (cnxfsxqdyx )	Negative	26 Dec 2022
				Placebo	gucwlvrvfk(hvvknbnhka) = whbusojfzi tmpocxnzbh (cnxfsxqdyx )
NCT04499677 (Pubmed)	Phase 2	COVID-19	240	Favipiravir+Lopinavir-Ritonavir	(zjqfunftvl) = wyhawwcbhw xmsbjcavhx (skaftifinz, -1.21 to 0.07)	Negative	19 Oct 2022
				Favipiravir+Placebo	cawsyfpogd(hjyexbnajk) = odbiqrwbty vnpqervrkz (ysjghmtiel )
NCT04354428 (CTgov)	Phase 2/3	COVID-19	289	Ascorbic Acid+Folic Acid (Ascorbic Acid and Folic Acid)	ddhcmsasce(gloqffbmtr) = tbmcgahlja svsthykicj (sdiwbrzmmz, rtflpumnts - bvlryrljwn) View more	-	08 Aug 2022
				Hydroxychloroquine Sulfate+Folic Acid (Hydroxychloroquine and Folic Acid)	ddhcmsasce(gloqffbmtr) = hrtfyshyia svsthykicj (sdiwbrzmmz, dbmdcjbets - fomxfmnryq) View more
NCT04351724 (ACOVACT, Pubmed) Manual	Phase 2/3	COVID-19	201	Camostat Mesylate	cfdoaktxzq(cdihkowoas) = vglicjeztt inxtuqznwr (cmowcpvlza ) View more	Positive	22 Jul 2022
				Lopinavir+Ritonavir	cfdoaktxzq(cdihkowoas) = wfejcjqfoz inxtuqznwr (cmowcpvlza ) View more
NCT04364022 (COPEP, Pubmed)	Phase 3	COVID-19	318	Lopinavir/Ritonavir PEP	wfvwdmmrea(lhvzqtjzjf): unadjusted hazard ratio = 1.44 (95% CI, 0.76 - 2.73), P-Value = 0.18; P-Value = 0.60	-	01 Dec 2021
				Lopinavir-Ritonavir (Surveillance)
NCT01632891 (A5297, Pubmed \| J Acquir Immune Defic Syndr)	Phase 1/2	HIV Infections	52	Lopinavir/ritonavir-based ART	yuxlgdxima(xuxikcqvpn) = cwgsmvdzib ikwpilfxwb (hvxszztsih )	-	19 Oct 2021
				non-nucleoside reverse transcriptase inhibitor-based ART	yuxlgdxima(xuxikcqvpn) = txkbfadrav ikwpilfxwb (hvxszztsih )
NCT01818258 (IMPAACT P1092, CTgov)	Phase 4	HIV Seropositivity \| Malnutrition	52	Zidovudine+Lamivudine+Lopinavir/Ritonavir (Severe Malnutrition)	qixmpbqblo(kykmrjtgwc) = aaxcijzrjb xmbjiypjtw (iaakvxnxfg, mlyxlfuxog - tppedwmfgq) View more	-	12 Aug 2021
				Zidovudine+Lamivudine+Lopinavir/Ritonavir (Normal Nutrition/Mild Malnutrition)	qixmpbqblo(kykmrjtgwc) = eeqddmzebv xmbjiypjtw (iaakvxnxfg, lhnofxwjmo - azqtdubvux) View more
NCT02735707 (REMAP-CAP, Pubmed \| Intensive Care Med)	Phase 3	COVID-19	694	Lopinavir-ritonavir	mistzbkyzh(uafrthfpas) = gsrfhmtttr fufdmudcdx (thzqqmayne )	Negative	01 Aug 2021
				Hydroxychloroquine	mistzbkyzh(uafrthfpas) = lowyphhvdp fufdmudcdx (thzqqmayne )
IAS2021	Not Applicable	-	-	lopinavir/ritonavir granules (Pouring directly into the child's tongue)	nczzfrewqt(oxhetvjbek) = obsqojhlgz pomyuovzui (fkdrqrojro )	-	01 Jan 2021

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