TMC114/ritonavir substitution for protease inhibitor(s) in a non-suppressive antiretroviral regimen: A 14-day proof-of-principle trial

AIDS

Volumn 19, Issue 9, 2005, Pages 943-947

  Arastéh, Keikawus ^a   Clumeck, Nathan ^b   Pozniak, Anton ^c   Lazzarin, Adriano ^d   De Meyer, Sandra ^e   Muller, Heidi ^e   Peeters, Monika ^e   Rinehart, Alex ^f   Lefebvre, Eric ^g  

^a Vivantes Auguste Viktoria Klinikum   (Germany)

^b SAINT PIERRE UNIVERSITY HOSPITAL   (Belgium)

^c CHELSEA AND WESTMINSTER HOSPITAL   (United Kingdom)

^d SAN RAFFAELE HOSPITAL   (Italy)

^e TIBOTEC BVBA   (Belgium)

^f VircoLab Inc   (United States)

^g Tibotec Inc   (United States)

Author keywords

Antiretroviral therapy; Clinical trials; HIV; Protease inhibitors; TMC114

Indexed keywords

AMPRENAVIR; DARUNAVIR; INDINAVIR; LOPINAVIR; NELFINAVIR; PROTEINASE INHIBITOR; RITONAVIR; SAQUINAVIR; VIRUS RNA;

ADULT; ANTIVIRAL ACTIVITY; ARTICLE; BLISTER; CENTRAL NERVOUS SYSTEM DISEASE; CLINICAL ARTICLE; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DOSE RESPONSE; DOSE TIME EFFECT RELATION; DRUG EFFECT; DRUG MECHANISM; DRUG SAFETY; DRUG TOLERABILITY; ECZEMA; FEMALE; GASTROINTESTINAL DISEASE; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; LIVER TOXICITY; LOW DRUG DOSE; MALE; MULTICENTER STUDY; OPEN STUDY; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; TREATMENT OUTCOME; TREATMENT WITHDRAWAL;

EID: 20644450806     PISSN: 02699370     EISSN: None     Source Type: Journal    
DOI: 10.1097/01.aids.0000171408.38490.01     Document Type: Article

References (12)

1. Murphy EL, Collier AC, Kalish LA, Assmann SF, Para MF, Flanigan TP, et al. Highly active antiretroviral therapy decreases mortality and morbidity in patients with advanced HIV disease. Ann Intern Med 2001; 135:17-26.
2. Hertogs K, Bloor S, Kemp SD, Van den Eynde C, Alcorn TM, Pauwels R, et al. Phenotypic and genotypic analysis of clinical HIV-1 isolates reveals extensive protease inhibitor cross-resistance: a survey of over 6000 samples. AIDS 2000; 14:1203-1210.
3. King NM, Prabu-Jeyabalan M, Nalivaika EA, Wigerinck P, de Bethune MP, Schiffer CA. Structural and thermodynamic basis for the binding of TMC114, a next-generation human immunodeficiency virus type 1 protease inhibitor. J Virol 2004; 78:12012-12021.
4. Koh Y, Nakata H, Maeda K, Ogata H, Bilcer G, Devasamudram T, et al. Novel bis-tetrahydrofuranylurethane-containing non-peptidic protease inhibitor (PI) UIC-94017 (TMC114) with potent activity against multi-PI-resistant human immunodeficiency virus in vitro. Antimicrob Agents Chemother 2003; 47:3123-3129.
5. De Meyer S, Azijn H, Surleraux D, Jochmans D, Tahri A, Pauwels R, et al. TMC114, a next-generation HIV-1 protease inhibitor active against protease inhibitor resistant viruses, including a broad range of clinical isolates. Antimicrob Agents Chemother, in press.
6. Tie Y, Boross PI, Wang YF, Gaddis L, Hussain AK, Leshchenko S, et al. High resolution crystal structures of HIV-1 protease with a potent non-peptide inhibitor (UIC-94017) active against multi-drug-resistant clinical strains. J Mol Biol 2004; 338:341-352.
7. Hoetelmans R, van der Sandt I, De Pauw M, Struble K, Peeters M, Van der Geest R. TMC114, a next generation HIV protease inhibitor: pharmacokinetics and safety following oral administration of multiple doses with and without low doses of ritonavir in healthy volunteers. 10th Conference on Retroviruses and Opportunistic Infections; Boston, February, 2003 [abstract 549].
8. D'Aquila RT, Schapiro JM, Brun-Vezinet F, Clotet B, Conway B, Demeter LM, et al. Drug resistance mutations in HIV-1. Top HIV Med 2003; 11:92-96.
9. Adult AIDS Clinical Trial Group (AACTG). Table for Grading Severity of Adult Adverse Experiences. Bethesda, MD: National Institute of Allergy and Infectious Diseases; 1992.
10. Hammer HF, Santa Ana CA, Schiller LR, Fordtran JS. Studies of osmotic diarrhea induced in normal subjects by ingestion of polyethylene glycol and lactulose. J Clin Invest 1989; 84:1056-1062.
11. Hoetelmans R, Lefebvre E, van der Sandt I, Marien K, De Pauw M, Peeters M, et al. Pharmacokinetics and effect of food on TMC114, a potent next generation protease inhibitor, boosted with low-dose ritonavir. 5th International Workshop on Clinical Pharmacology of HIV Therapy. Rome April 2004 [poster 5.6].
12. Harrigan PR, Montaner JS, Wegner SA, Verbiest W, Miller V, Wood R, et al. World-wide variation in HIV-1 phenotypic susceptibility in untreated individuals: biologically relevant values for resistance testing. AIDS 2001; 15:1671-1677.