Antiretroviral activity, pharmacokinetics, and tolerability of MK-0518, a novel inhibitor of HIV-1 integrase, dosed as monotherapy for 10 days in treatment-naive HIV-1-infected individuals

Journal of Acquired Immune Deficiency Syndromes

Volumn 43, Issue 5, 2006, Pages 509-515

  Markowitz, Martin ^a   Morales Ramirez, Javier O ^b   Nguyen, Bach Yen ^c   Kovacs, Colin M ^d   Steigbigel, Roy T ^e   Cooper, David A ^f   Liporace, Ralph ^g   Schwartz, Robert ^h   Isaacs, Robin ^c   Gilde, Lucinda R ^c   Wenning, Larissa ^c   Zhao, Jing ^c   Teppler, Hedy ^c   Tsoukas, C ⁱ   Galpin, J ^j   Hicks, C ^k   Brown, S ^l   Chen, J ^c   Miller, M ^c   Hazuda, D ^c   Vacca, J ^c   Iwamoto, M ^c   Rowley, M ^m   Summa, V ^m   more..

^a ROCKEFELLER UNIVERSITY   (United States)

^b Clinical Research Puerto Rico Inc   (Puerto Rico)

^c MERCK RESEARCH LABORATORIES   (United States)

^d Canadian Immunodeficiency Research Collaborative   (Canada)

^e STONY BROOK UNIVERSITY   (United States)

^f UNIVERSITY OF NEW SOUTH WALES   (Australia)

^g ALBANY MEDICAL COLLEGE   (United States)

^h Associates in Research   (United States)

ⁱ MONTREAL GENERAL HOSPITAL   (Canada)

^j Shared Medical Research Foundation   (United States)

^k DUKE UNIVERSITY MEDICAL CENTER   (United States)

^l AIDS Research Alliance   (United States)

^m IRBM   (Italy)

more..

Author keywords

AIDS; Antiretroviral therapy; HIV 1; Integrase inhibitor; MK 0518

Indexed keywords

INTEGRASE; INTEGRASE INHIBITOR; MK 0518; PLACEBO; VIRUS RNA;

ALANINE AMINOTRANSFERASE BLOOD LEVEL; ANOREXIA; ANTIVIRAL ACTIVITY; ARTICLE; AUSTRALIA; CANADA; CHILL; CLINICAL ARTICLE; CLINICAL TRIAL; CONSTIPATION; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DISORIENTATION; DIZZINESS; DOSE RESPONSE; DOUBLE BLIND PROCEDURE; DRUG BLOOD LEVEL; DRUG DOSE COMPARISON; DRUG EFFECT; DRUG SAFETY; DRUG TOLERABILITY; FATIGUE; FEMALE; FLATULENCE; HEADACHE; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; HYPERHIDROSIS; LABORATORY TEST; MALAISE; MALE; MONOTHERAPY; MULTICENTER STUDY; PATIENT MONITORING; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; SIDE EFFECT; STEADY STATE; STOMACH DISCOMFORT; TACHYCARDIA; TREATMENT DURATION; UNITED STATES;

ADULT; AREA UNDER CURVE; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; DRUG ADMINISTRATION SCHEDULE; FEMALE; HIV INFECTIONS; HIV INTEGRASE; HIV INTEGRASE INHIBITORS; HIV-1; HUMANS; MALE; MIDDLE AGED; ORGANIC CHEMICALS; RNA, VIRAL; VIRAL LOAD;

EID: 33845366857     PISSN: 15254135     EISSN: None     Source Type: Journal    
DOI: 10.1097/QAI.0b013e31802b4956     Document Type: Article

References (20)

1. Palella FJ Jr, Delaney KM, Moorman AC, et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. N Engl J Med. 1998;338:853-860.
2. Mocroft A, Vella S, Benfield TL, et al. Changing patterns of mortality across Europe in patients infected with HIV-1. Eurosida Study Group. Lancet. 1998;352:1725-1730.
3. Shet A, Berry L, Mohri H, et al. Tracking the prevalence of transmitted antiretroviral drug-resistant HIV-1 - a decade of experience. J Acquir Immune Defic Syndr. 2006;41:439-446.
4. Johnson N, Mullings AA, Harvey KM, et al. HIV seroprevalence, uptake of interventions to reduce mother-to-child transmission and birth outcomes in Greater Kingston, Jamaica. West Indian Med J. 2004;53:297-302.
5. Viani R, Peralta L, Aldrovandi G, et al. Prevalence of primary HIV drug resistance among recently infected adolescents; a Multicenter Adolescent Trials Network Study: ATN029. Presented at: 13th Conference on Retroviruses and Opportunistic Infections; 2006; Denver.
6. Esposito D, Craigie R. HIV integrase structure and function. Adv Virus Res. 1999;52:319-333.
7. Asante-Appiah E, Skalka AM. HIV-1 integrase: structural organization, conformational changes, and catalysis. Adv Virus Res. 1999;52:351-369.
8. Hazuda DJ, Felock P, Witmer M, et al. Inhibitors of strand transfer that prevent integration and inhibit HIV-1 replication in cells. Science. 2000;287:646-650.
9. Hazuda DJ, Young S, Guare JP, et al. Integrase inhibitors and cellular immunity suppress retroviral replication in rhesus macaques. Science. 2004;305:528-532.
10. Miller MD, Witmer MV, Stillmock KA, et al. Biochemical and antiviral activity of MK-0518, a potent HIV integrase inhibitor. Presented at: AIDS 16th International Conference; 2006; Toronto.
11. Summa V, Pace P, Petrocchi A, et al. Discovery of MK-0518 a novel, potent and selective HIV integrase inhibitor in phase III clinical trials. Presented at: AIDS 16th International Conference; 2006; Toronto.
12. Morales-Ramirez JO, Teppler H, Kovacs C, et al. Antiretroviral effect of MK-0518, a novel HIV-1 integrase inhibitor, in ART-naive HIV-1 infected patients. Presented at: 10th European AIDS Conference; 2005; Dublin.
13. Petry A, Wenning LA, Laethem T, et al. Safety, tolerability, and pharmacokinetics after single and multiple doses of MK-0518 in healthy subjects. Presented at: Interscience Conference on Antimicrobial Agents and Chemotherapy 46th Annual Meeting; 2006; San Francisco.
14. Ho DD, Neumann AU, Perelson AS, et al. Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection. Nature. 1995;373:123-126.
15. Perelson AS, Essunger P, Cao Y, et al. Decay characteristics of HIV-1-infected compartments during combination therapy. Nature. 1997;387:188-191.
16. Louie M, Hogan C, Hurley A. Determining the antiviral activity of tenofovir disoproxil fumarate in treatment-naive chronically HIV-1-infected individuals. AIDS. 2003;17:1-6.
17. Ventura J, Wenning LA, Troyer MD, et al. Lack of a pharmacokinetic interaction of MK-0518 on midazolam (MDZ). Presented at: Eighth International Congress on Drug Therapy in HIV Infection; 2006; Glasgow.
18. Kassahun K, McIntosh IS, Hreniuk D, et al. Absorption, metabolism and excretion of MK-0518, a potent HIV-1 integrase inhibitor, in healthy male volunteers. Presented at: Interscience Conference on Antimicrobial Agents and Chemotherapy 46th Annual Meeting; 2006; San Francisco.
19. Markowitz M, Nguyen B-Y, Gotuzzo E, et al. Potent antiretroviral effect of MK-0518, a novel HIV-1 integrase inhibitor, as part of combination ART in treatment-naïve HIV-1 infected patients. Presented at: XVI International AIDS Conference; 2006; Toronto.
20. Grinsztejn B, Nguyen B-Y, Katlama C, et al. Potent antiretroviral effect of MK-0518, a novel HIV-1 integrase inhibitor, in patients with triple-class resistant virus. Presented at: 13th Conference on Retrovirus and Opportunistic Infections; 2006; Denver.