scholarly journals Brain Perfusion, Regional Volumes, and Cognitive Function in Human Immunodeficiency Virus–positive Patients Treated With Protease Inhibitor Monotherapy

2018 ◽  
Vol 68 (6) ◽  
pp. 1031-1040 ◽  
Author(s):  
Lewis J Haddow ◽  
Claudia Godi ◽  
Magdalena Sokolska ◽  
M Jorge Cardoso ◽  
Ruth Oliver ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Cognitive Function ◽  
Protease Inhibitor ◽  
Brain Perfusion ◽  
Immunodeficiency Virus ◽  
Protease Inhibitor Monotherapy

scholarly journals Elevated Levels of Estradiol in Human Immunodeficiency Virus–Infected Pregnant Women on Protease Inhibitor–Based Regimens

2017 ◽  
Vol 66 (3) ◽  
pp. 420-427 ◽  
Author(s):  
Kayode A Balogun ◽  
Monica S Guzman Lenis ◽  
Eszter Papp ◽  
Mona Loutfy ◽  
Mark H Yudin ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Protease Inhibitor ◽  
Pregnant Women ◽  
Immunodeficiency Virus

scholarly journals Novel bis-Tetrahydrofuranylurethane-Containing Nonpeptidic Protease Inhibitor (PI) UIC-94017 (TMC114) with Potent Activity against Multi-PI-Resistant Human Immunodeficiency Virus In Vitro

2003 ◽  
Vol 47 (10) ◽  
pp. 3123-3129 ◽  
Author(s):  
Yasuhiro Koh ◽  
Hirotomo Nakata ◽  
Kenji Maeda ◽  
Hiromi Ogata ◽  
Geoffrey Bilcer ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Protease Inhibitor ◽  
Therapeutic Agent ◽  
Close Contact ◽  
Wide Spectrum ◽  
Antiviral Agents ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT We designed, synthesized, and identified UIC-94017 (TMC114), a novel nonpeptidic human immunodeficiency virus type 1 (HIV-1) protease inhibitor (PI) containing a 3(R),3a(S),6a(R)-bis-tetrahydrofuranylurethane (bis-THF) and a sulfonamide isostere which is extremely potent against laboratory HIV-1 strains and primary clinical isolates (50% inhibitory concentration [IC50], ∼0.003 μM; IC90, ∼0.009 μM) with minimal cytotoxicity (50% cytotoxic concentration for CD4+ MT-2 cells, 74 μM). UIC-94017 blocked the infectivity and replication of each of HIV-1NL4-3 variants exposed to and selected for resistance to saquinavir, indinavir, nelfinavir, or ritonavir at concentrations up to 5 μM (IC50s, 0.003 to 0.029 μM), although it was less active against HIV-1NL4-3 variants selected for resistance to amprenavir (IC50, 0.22 μM). UIC-94017 was also potent against multi-PI-resistant clinical HIV-1 variants isolated from patients who had no response to existing antiviral regimens after having received a variety of antiviral agents. Structural analyses revealed that the close contact of UIC-94017 with the main chains of the protease active-site amino acids (Asp-29 and Asp-30) is important for its potency and wide spectrum of activity against multi-PI-resistant HIV-1 variants. Considering the favorable pharmacokinetics of UIC-94017 when administered with ritonavir, the present data warrant that UIC-94017 be further developed as a potential therapeutic agent for the treatment of primary and multi-PI-resistant HIV-1 infections.

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