WO2004060370A1 - Treatment of hiv infection through combined administration of tipranavir and capravirine - Google Patents

Treatment of hiv infection through combined administration of tipranavir and capravirine Download PDF

Info

Publication number
WO2004060370A1
WO2004060370A1 PCT/US2003/037745 US0337745W WO2004060370A1 WO 2004060370 A1 WO2004060370 A1 WO 2004060370A1 US 0337745 W US0337745 W US 0337745W WO 2004060370 A1 WO2004060370 A1 WO 2004060370A1
Authority
WO
WIPO (PCT)
Prior art keywords
tipranavir
treatment
capravirine
hiv infection
combination
Prior art date
Application number
PCT/US2003/037745
Other languages
French (fr)
Inventor
Ulrich Walter Drees
Douglas Lytle Mayers
Scott Mccallister
Original Assignee
Boehringer Ingelheim Pharmaceuticals, Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Boehringer Ingelheim Pharmaceuticals, Inc. filed Critical Boehringer Ingelheim Pharmaceuticals, Inc.
Priority to EP03787155A priority Critical patent/EP1575583A1/en
Priority to CA002509731A priority patent/CA2509731A1/en
Priority to AU2003295940A priority patent/AU2003295940A1/en
Priority to JP2004565110A priority patent/JP2006514045A/en
Publication of WO2004060370A1 publication Critical patent/WO2004060370A1/en

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A61K31/52—Purines, e.g. adenine
    • A61K31/522—Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/7056—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing five-membered rings with nitrogen as a ring hetero atom
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/18—Antivirals for RNA viruses for HIV
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • the present invention relates to an improved method for treating HIV infection comprising administering to a human in need of such treatment a combination of a therapeutically effective amount of tipranavir or a pharmaceutically acceptable salt thereof, and a therapeutically effective amount of capravirine or a pharmaceutically acceptable salt thereof.
  • HIV Human immunodeficiency virus
  • NRTIs Nucleoside Reverse Transcriptase Inhibitors
  • QSTNRTIs Non- nucleoside Reverse Transcriptase Inhibitors
  • Protease Inhibitors Protease Inhibitors
  • combination therapies i.e. the selection of two or more antiretroviral agents taken together to make up a "drug cocktail," are the preferred treatment for HIV infection.
  • Combination therapies have been shown to reduce the incidence of opportunistic infections and to increase survival time.
  • the drug cocktail combines drugs from different classes, so as to attack the virus at several stages in the replication process.
  • Tipranavir and capravirine are both known agents for the treatment of HIV infection.
  • Tipranavir also known as U-140690 and PNU-140690, is an HIV protease inhibitor.
  • tipranavir is (6R)-3-((lR)-l-[3-( ⁇ [5-trifluoromethyl)(2- pyridyl)]sulfonyl ⁇ amino)phenyl]propyl ⁇ -4-hydroxy-6-(2-phenylethyl)-6-propyl-5,6- dihydro-2H-pyran-2-one or ([R-(R*,R*)]-N-[3-[l-[5,6-dihydro-4-hydroxy-2-oxo-6-(2- phenylethyl)-6-prop yl-2H-pyran-3-yl]propyl]phenyl]-5-(trifluoromethyl)-2- pyridinesulfonamide). It has the following structural formula:
  • Tipranavir and methods for its synthesis and use in the treatment of HTV are described in WO 95/30670 and corresponding U.S. Patent 5,852,195.
  • Pharmaceutical formulations suitable for the oral administration of tipranavir are described in WO 99/06043 and WO 99/06044, and the corresponding U.S. Patents 6,121,313 and 6,231,887.
  • Capravirine (CAS REGISTRY NUMBER 178979-85-6), also known as AG 1549 and S 1153, is an HIV NNRTI. Chemically, capravirine is, 5-[(3,5-dichlorophenyl)thio]-4-(l- methylemyl)-l-(4-pyridinylmethyl)-lH-irnidazole-2-methanol carbamate ester. It has the following structural formula:
  • the present invention provides an improved method for treating highly treatment experienced HlV-infected patients.
  • the method comprises administering tipranavir in combination with an iiihibitor of Cyp3A4 (such as ritonavir), in further combination with capravirine and an optimized background regimen of nucleoside reverse transcriptase inhibitors to provide an active antiretroviral regimen.
  • an iiihibitor of Cyp3A4 such as ritonavir
  • the present invention provides an improved method for treating HIV infection, especially in highly treatment experienced HTV-infected patients.
  • the method comprises administering tipranavir in combination with an inhibitor of Cyp3A4, in further combination with capravirine and an optimized background regimen of nucleoside reverse transcriptase inhibitors to provide an active antiretroviral regimen that is particulary well suited for the treatment of highly treatment experienced HIN-infected patients.
  • highly treatment experienced HIV-infected patients means HIV-infected patients with virologic failure (detectable HIV R ⁇ A in their blood) who have previously received treatment with 2 or more combination antiretroviral regimens.
  • the term "optimized background regimen of nucleoside reverse transcriptase inhibitors” means a combination of nucleoside or nucleotide agents selected on the basis of all of the information available to the treating provider including drug history, knowledge of resistance/ cross resistance and, where available, genotypic or phenotypic drug resistance test results for the virus in the HTV-infected patient's blood.
  • tipranavir When employed in accordance with the method of the invention, tipranavir can be administered in the manner described in WO 95/30670 and corresponding U.S. Patent 5,852,195. It is preferred to administer this substance orally using pharmaceutical formulations such as those described in WO 99/06043 and WO 99/06044, and the corresponding U.S. Patents 6,121,313 and 6,231,887. It is particularly preferred to administer the tipranavir at the dosage of 500 to 750 mg PO BID.
  • a suitable inhibitor of Cyp3A4 is ritonavir, which can be administered as described in U.S. Patent 6,147,095.
  • ritonavir For the purposes of the present invention it is preferred to administer ritonavir at a dosage of 200 mg PO BID.
  • the use for this purpose of other inhibitors of Cyp3A4 is also possible.
  • capravirine is administered in the manner described in U.S. Patent 5,910,506.
  • the preferred dosage of capravirine will range from 400 to 1400 mg PO BID.
  • nucleoside and nucleotide reverse transcriptase inhibitors will be given at standard doses, in the manner known to those of routine skill in the clinical treatment of HIV infection.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Molecular Biology (AREA)
  • Virology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • AIDS & HIV (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

An improved method for treating HIV infection comprising administering to a human in need of such treatment a combination of a therapeutically effective amount of tipranavir or a pharmaceutically acceptable salt thereof, and a therapeutically effective amount of capravirine or a pharmaceutically acceptable salt thereof.

Description

TREATMENT OF HIV INFECTION THROUGH COMBINED ADMINISTRATION OF
TIPRANAVIR AND C APRAVIRINE
FIELD OF THE INVENTION
The present invention relates to an improved method for treating HIV infection comprising administering to a human in need of such treatment a combination of a therapeutically effective amount of tipranavir or a pharmaceutically acceptable salt thereof, and a therapeutically effective amount of capravirine or a pharmaceutically acceptable salt thereof.
BACKGROUND OF THE INVENTION
Human immunodeficiency virus (HIV) is recognized as the causative agent in AIDS.
Current therapies for HIV infection focus on inhibiting the activity of viral enzymes which are essential to the life cycle of the virus. The agents that are presently in use fall mainly into three classes, designated Nucleoside Reverse Transcriptase Inhibitors (NRTIs), Non- nucleoside Reverse Transcriptase Inhibitors QSTNRTIs), and Protease Inhibitors (Pis). Presently, combination therapies, i.e. the selection of two or more antiretroviral agents taken together to make up a "drug cocktail," are the preferred treatment for HIV infection. Combination therapies have been shown to reduce the incidence of opportunistic infections and to increase survival time. Typically, the drug cocktail combines drugs from different classes, so as to attack the virus at several stages in the replication process. This approach has been shown to reduce the likelihood of the development of virus forms that are resistant to a given drug or class of drugs. Treatment failure with rebound of the amount of HIV which can be measured in the blood is common for patients treated with combination antiretroviral regimens. Resistance to the drugs in the drug regimen develops as the virus replicates in the presence of these drugs. Because of structural similarities of the drugs within an antiretroviral class, cross resistance is commonly seen to the other members of that class (for example virologic failure on a regimen containing an NNRTI will lead to cross resistance to the other first generation NNRTI agents). As patients experience repeated virologic failure on antiretroviral combination therapy, their viruses develop broad multi-class antiretroviral drug resistance which limits the effectiveness of the next round of antiretroviral therapy. Many highly treatment experienced patients have been exposed to all three classes of antiretroviral drugs and cannot obtain two active drugs to form the core of a new, effective antiretroviral drug regimen.
Tipranavir and capravirine are both known agents for the treatment of HIV infection.
Tipranavir, also known as U-140690 and PNU-140690, is an HIV protease inhibitor. Chemically, tipranavir is (6R)-3-((lR)-l-[3-({[5-trifluoromethyl)(2- pyridyl)]sulfonyl}amino)phenyl]propyl}-4-hydroxy-6-(2-phenylethyl)-6-propyl-5,6- dihydro-2H-pyran-2-one or ([R-(R*,R*)]-N-[3-[l-[5,6-dihydro-4-hydroxy-2-oxo-6-(2- phenylethyl)-6-prop yl-2H-pyran-3-yl]propyl]phenyl]-5-(trifluoromethyl)-2- pyridinesulfonamide). It has the following structural formula:
Figure imgf000003_0001
Tipranavir, and methods for its synthesis and use in the treatment of HTV are described in WO 95/30670 and corresponding U.S. Patent 5,852,195. Pharmaceutical formulations suitable for the oral administration of tipranavir are described in WO 99/06043 and WO 99/06044, and the corresponding U.S. Patents 6,121,313 and 6,231,887.
As tipranavir is metabolized relatively rapidly by the the cytochromes P450, especially the Cyp3A4 isoform, it is necessary to co-administer an inhibitor of Cyp3A4 in order to obtain therapeutically effective blood levels of tipranavir. The use of ritonavir for this purpose is described in U.S. Patent 6,147,095. The use for this purpose of other inhibitors of Cyp3A4 is possible.
Capravirine (CAS REGISTRY NUMBER 178979-85-6), also known as AG 1549 and S 1153, is an HIV NNRTI. Chemically, capravirine is, 5-[(3,5-dichlorophenyl)thio]-4-(l- methylemyl)-l-(4-pyridinylmethyl)-lH-irnidazole-2-methanol carbamate ester. It has the following structural formula:
Figure imgf000004_0001
Capravirine, methods for its synthesis and use in the treatment of HTV, and pharmaceutical preparations suitable for carrying out such treatment, are described in U.S. Patent 5,910,506.
SUMMARY OF THE INVENTION
The present invention provides an improved method for treating highly treatment experienced HlV-infected patients. The method comprises administering tipranavir in combination with an iiihibitor of Cyp3A4 (such as ritonavir), in further combination with capravirine and an optimized background regimen of nucleoside reverse transcriptase inhibitors to provide an active antiretroviral regimen. DETAILED DESCRIPTION OF THE INVENTION
The present invention provides an improved method for treating HIV infection, especially in highly treatment experienced HTV-infected patients. The method comprises administering tipranavir in combination with an inhibitor of Cyp3A4, in further combination with capravirine and an optimized background regimen of nucleoside reverse transcriptase inhibitors to provide an active antiretroviral regimen that is particulary well suited for the treatment of highly treatment experienced HIN-infected patients.
As used herein, the term "highly treatment experienced HIV-infected patients" means HIV-infected patients with virologic failure (detectable HIV RΝA in their blood) who have previously received treatment with 2 or more combination antiretroviral regimens.
As used herein, the term "optimized background regimen of nucleoside reverse transcriptase inhibitors" means a combination of nucleoside or nucleotide agents selected on the basis of all of the information available to the treating provider including drug history, knowledge of resistance/ cross resistance and, where available, genotypic or phenotypic drug resistance test results for the virus in the HTV-infected patient's blood.
When employed in accordance with the method of the invention, tipranavir can be administered in the manner described in WO 95/30670 and corresponding U.S. Patent 5,852,195. It is preferred to administer this substance orally using pharmaceutical formulations such as those described in WO 99/06043 and WO 99/06044, and the corresponding U.S. Patents 6,121,313 and 6,231,887. It is particularly preferred to administer the tipranavir at the dosage of 500 to 750 mg PO BID.
A suitable inhibitor of Cyp3A4 is ritonavir, which can be administered as described in U.S. Patent 6,147,095. For the purposes of the present invention it is preferred to administer ritonavir at a dosage of 200 mg PO BID. The use for this purpose of other inhibitors of Cyp3A4 is also possible. When used in accordance with the present invention, capravirine is administered in the manner described in U.S. Patent 5,910,506. The preferred dosage of capravirine will range from 400 to 1400 mg PO BID.
Concomitantly administered nucleoside and nucleotide reverse transcriptase inhibitors will be given at standard doses, in the manner known to those of routine skill in the clinical treatment of HIV infection.

Claims

What is claimed is:
1. An improved method for treating highly treatment experienced HTV-infected patients, which method comprises administering tipranavir in combination with an inhibitor of Cyp3A4.
2. The method of claim 1 wherein the inhibitor of Cyp3 A4 is ritonavir.
3. The method of claim 1 wherein the tipranavir, inhibitor of Cyp3 A4 and capravirine are administered in further combination with an optimized background regimen comprising at least one nucleoside reverse transcriptase inhibitor.
PCT/US2003/037745 2002-12-16 2003-11-24 Treatment of hiv infection through combined administration of tipranavir and capravirine WO2004060370A1 (en)

Priority Applications (4)

Application Number Priority Date Filing Date Title
EP03787155A EP1575583A1 (en) 2002-12-16 2003-11-24 Treatment of hiv infection through combined administration of tipranavir and capravirine
CA002509731A CA2509731A1 (en) 2002-12-16 2003-11-24 Treatment of hiv infection through combined administration of tipranavir and capravirine
AU2003295940A AU2003295940A1 (en) 2002-12-16 2003-11-24 Treatment of hiv infection through combined administration of tipranavir and capravirine
JP2004565110A JP2006514045A (en) 2002-12-16 2003-11-24 Treatment of HIV infection by combined administration of tipranavir and capravirin

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US43367902P 2002-12-16 2002-12-16
US60/433,679 2002-12-16

Publications (1)

Publication Number Publication Date
WO2004060370A1 true WO2004060370A1 (en) 2004-07-22

Family

ID=32712988

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2003/037745 WO2004060370A1 (en) 2002-12-16 2003-11-24 Treatment of hiv infection through combined administration of tipranavir and capravirine

Country Status (6)

Country Link
US (1) US20050020517A1 (en)
EP (1) EP1575583A1 (en)
JP (1) JP2006514045A (en)
AU (1) AU2003295940A1 (en)
CA (1) CA2509731A1 (en)
WO (1) WO2004060370A1 (en)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2903312B1 (en) 2006-07-05 2008-09-26 Univ Aix Marseille Ii USE OF INHIBITORS OF HMG-COA REDUCTASE AND FARNESYL-PYROPHOSPHATE SYNTHASE IN THE PREPARATION OF A MEDICINAL PRODUCT
JP5570999B2 (en) * 2008-01-03 2014-08-13 ユニベルシテ デ―マルセイユ Composition for use in anti-HIV therapy

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998045276A2 (en) * 1997-04-09 1998-10-15 Du Pont Pharmaceuticals Company 4,4-disubstituted-3,4-dihydro-2(1h)-quinazolinones useful as hiv reverse transcriptase inhibitors
WO2000025784A1 (en) * 1998-11-04 2000-05-11 Pharmacia & Upjohn Company Method for improving the pharmacokinetics of tipranavir
US6124302A (en) * 1997-04-09 2000-09-26 Dupont Pharmaceuticals 4,4-disubstituted-3,4-dihydro-2(1H)-quinazolinones useful as HIV reverse transcriptase inhibitors

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998045276A2 (en) * 1997-04-09 1998-10-15 Du Pont Pharmaceuticals Company 4,4-disubstituted-3,4-dihydro-2(1h)-quinazolinones useful as hiv reverse transcriptase inhibitors
US6124302A (en) * 1997-04-09 2000-09-26 Dupont Pharmaceuticals 4,4-disubstituted-3,4-dihydro-2(1H)-quinazolinones useful as HIV reverse transcriptase inhibitors
WO2000025784A1 (en) * 1998-11-04 2000-05-11 Pharmacia & Upjohn Company Method for improving the pharmacokinetics of tipranavir
US6147095A (en) * 1998-11-04 2000-11-14 Pharmacia & Upjohn Company Method for improving the pharmacokinetics of tipranavir

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
CHONG K-T ET AL: "IN VITRO COMBINATION OF PNU-140690, A HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 PROTEASE INHIBITOR, WITH RITONAVIR AGAINST RITONAVIR-SENSITIVE AND -RESISTANT CLINICAL ISOLATES", ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, AMERICAN SOCIETY FOR MICROBIOLOGY, WASHINGTON, DC, US, vol. 41, no. 11, November 1997 (1997-11-01), pages 2367 - 2373, XP000901461, ISSN: 0066-4804 *
CLERCQ DE E: "NEW ANTI-HIV AGENTS AND TARGETS", MEDICINAL RESEARCH REVIEWS, NEW YORK, NY, US, vol. 22, no. 6, 2002, pages 531 - 565, XP009011727, ISSN: 0198-6325 *
CLERCQ DE E: "NEW DEVELOPMENTS IN ANTI-HIV CHEMOTHERAPY", CURRENT MEDICINAL CHEMISTRY, BENTHAM SCIENCE PUBLISHERS BV, BE, vol. 8, no. 13, November 2001 (2001-11-01), pages 1543 - 1572, XP009012547, ISSN: 0929-8673 *
YENI PATRICK: "Tipranavir: A protease inhibitor from a new class with distinct antiviral activity.", JAIDS JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES, vol. 34, no. Supplement 1, September 2003 (2003-09-01), pages S91 - S94, XP002275552, ISSN: 1525-4135 (ISSN print) *

Also Published As

Publication number Publication date
EP1575583A1 (en) 2005-09-21
CA2509731A1 (en) 2004-07-22
AU2003295940A1 (en) 2004-07-29
JP2006514045A (en) 2006-04-27
US20050020517A1 (en) 2005-01-27

Similar Documents

Publication Publication Date Title
Benson et al. Safety and antiviral activity at 48 weeks of lopinavir/ritonavir plus nevirapine and 2 nucleoside reverse-transcriptase inhibitors in human immunodeficiency virus type 1-infected protease inhibitor-experienced patients
Wiznia et al. Combination nucleoside analog reverse transcriptase inhibitor (s) plus nevirapine, nelfinavir, or ritonavir in stable antiretroviral therapy-experienced HIV-infected children: Week 24 results of a randomized controlled trial-PACTG 377
Heneine et al. HIV prevention by oral preexposure prophylaxis
Pacanowski et al. Atazanavir urinary stones in an HIV-infected patient
Stolte-Leeb et al. Topical nonnucleoside reverse transcriptase inhibitor MC 1220 partially prevents vaginal RT-SHIV infection of macaques
WO2006043153A2 (en) Use of zinc and copper chelators for the treatment of viral diseases
Singh et al. The promise of dolutegravir: a novel second generation integrase strand transfer inhibitor
EP1575583A1 (en) Treatment of hiv infection through combined administration of tipranavir and capravirine
Bonacini et al. Highly active antiretroviral therapy-induced liver injury
Catamancio et al. HIV-1 protease inhibitors in development
Lalezari et al. Selecting the optimum dose for a new soft gelatin capsule formulation of saquinavir
Deeks Failure of HIV-1 protease inhibitors to fully suppress viral replication: implications for salvage therapy
US6251874B1 (en) Method of inhibiting human immunodeficiency virus using hydroxurea and a reverse transcriptase inhibitor in vivo
JP2004083576A (en) Use of chloroquine, hydroxychloroquine, and 4-amino-quinolinic acid derivative for obtaining anti-retrovirus therapeutic agent having activity against hiv strain
RU2393872C2 (en) Hiv-infection treatment by t-cell modulation
Harris Efficacy and Durability of Nevirapine in anti-retroviral-Experienced Patients
Machado et al. Successful desensitization of enfuvirtide after a first attempt failure
Willyard An unknown enemy
Ruane et al. Pilot study of once-daily simplification therapy with abacavir/lamivudine/zidovudine and efavirenz for treatment of HIV-1 infection
Chokekijchai et al. In vitro anti-HIV-1 activity of HIV protease inhibitor KNI-272 in resting and activated cells: implications for its combined use with AZT or ddI
Kawade et al. AIDS THERAPY: INFLUENCE ON NEW DRUGS
Cainelli et al. Lymph nodes and pathogenesis of infection with HIV-1
JP2008520701A (en) Method for treating HIV infection through simultaneous administration of tipranavir and liver set
Alvarez et al. Critical appraisal and update on tenofovir in management of human immunodeficiency virus infection
August et al. HIV I: Molecular biology and pathogenesis: clinical applications

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BW BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE EG ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NI NO NZ OM PG PH PL PT RO RU SC SD SE SG SK SL SY TJ TM TN TR TT TZ UA UG UZ VC VN YU ZA ZM ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): BW GH GM KE LS MW MZ SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IT LU MC NL PT RO SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
121 Ep: the epo has been informed by wipo that ep was designated in this application
WWE Wipo information: entry into national phase

Ref document number: 2003787155

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: 2509731

Country of ref document: CA

WWE Wipo information: entry into national phase

Ref document number: 2004565110

Country of ref document: JP

WWP Wipo information: published in national office

Ref document number: 2003787155

Country of ref document: EP