Safety, tolerability, and efficacy of KP-1461 as monotherapy for 124 days in antiretroviral-experienced, HIV type 1-infected subjects

AIDS Research and Human Retroviruses

Volumn 29, Issue 2, 2013, Pages 250-255

  Hicks, Charles ^a   Clay, Patrick ^b   Redfield, Robert ^c   Lalezari, Jay ^d   Liporace, Ralph ^e   Schneider, Stefan ^f   Sension, Michael ^g   Mcrae, MaryPeace ^b   Laurent, Jean Pierre ^h  

^a DUKE UNIVERSITY MEDICAL CENTER   (United States)

^b UNIVERSITY OF MISSOURI KANSAS CITY   (United States)

^c UNIVERSITY OF MARYLAND SCHOOL OF MEDICINE   (United States)

^d UNIVERSITY OF CALIFORNIA   (United States)

^e ALBANY MEDICAL COLLEGE   (United States)

^f ST MARY MEDICAL CENTER   (United States)

^g BROWARD HEALTH MEDICAL CENTER   (United States)

^h Koronis Pharma Inc   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT; KP 1461; NONNUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR; PROTEINASE INHIBITOR; RNA DIRECTED DNA POLYMERASE INHIBITOR; UNCLASSIFIED DRUG;

ADULT; ANTIVIRAL ACTIVITY; ANTIVIRAL RESISTANCE; ANTIVIRAL SUSCEPTIBILITY; ARTICLE; BASE PAIRING; CD4 LYMPHOCYTE COUNT; CLINICAL ARTICLE; CONTROLLED STUDY; DIZZINESS; DRUG EFFICACY; DRUG EXPOSURE; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; DYSGEUSIA; ESOPHAGITIS; FATIGUE; FEMALE; GASTROINTESTINAL DISEASE; HEADACHE; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; HUMAN IMMUNODEFICIENCY VIRUS INFECTED PATIENT; IN VIVO STUDY; INFECTION; INFESTATION; MALE; MONOTHERAPY; MULTICENTER STUDY; NAUSEA; NEUROLOGIC DISEASE; PATIENT COMPLIANCE; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; RESPIRATORY TRACT DISEASE; SIDE EFFECT; SINUSITIS; SKIN DISEASE; SORE THROAT; TREATMENT DURATION; TREATMENT OUTCOME; UPPER RESPIRATORY TRACT INFECTION; VIRUS LOAD; VIRUS MUTATION;

ADULT; ANTI-HIV AGENTS; CD4 LYMPHOCYTE COUNT; DRUG TOXICITY; FEMALE; HIV INFECTIONS; HUMANS; MALE; MIDDLE AGED; MUTATION; NUCLEOSIDES; RNA, VIRAL; SEQUENCE ANALYSIS, DNA; TREATMENT OUTCOME; VIRAL LOAD;

EID: 84872951243     PISSN: 08892229     EISSN: 19318405     Source Type: Journal    
DOI: 10.1089/aid.2012.0093     Document Type: Article

References (15)

1. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Accessed via http://aidsinfo .nih.gov/Guidelines/ GuidelineDetail. Accessed on March 29, 2012.
2. Thompson MA, Aberg JA, Cahn P, et al.: Antiretroviral treatment of adult HIV infection: 2010 recommendations of the International AIDS Society-USA panel. JAMA 2010;304: 321-333.
3. Mocraft 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. (Pubitemid 28534954)
4. Hogg RS, Yip B, Chan KJ, et al.: Rates of disease progression by baseline CD4 cell count and viral load after initiating triple drug therapy. JAMA. 2001;286(20): 2568-2577. (Pubitemid 33096808)
5. Palella FJ Jr, Deloria-Knoll M, Chmiel JS, et al.: Survival benefit of initiating antiretroviral therapy in HIV-infected persons in different CD4 strata. Ann Intern Med 2003; 138:620-626.
6. Hirsch MS, Gunthard HF, Schapiro JM, et al.: Antiretroviral drug resistance testing in adult HIV-1 infection: 2008 recommendations of an International AIDS Society-USA panel. Clin Infect Dis 2008;47:266-285. (Pubitemid 351920631)
7. Palella FJ Jr, Armon C, Buchacz K, et al.: The association of HIV susceptibility testing with survival among HIV-infected patients receiving antiretroviral therapy: A cohort study. Ann Intern Med 2009;151:73-84.
8. Chun TW, Engel D, Berrey MM, et al.: Early establishment of a pool of latently infected, resting CD4 (+) T cells during primary HIV-1 infection. Proc Natl Acad Sci USA 1998; 95:8869-8873. (Pubitemid 28350581)
9. Loeb LA, Essigmann JM, Kazazi F, et al.: Lethal mutagenesis of HIV with mutagenic nucleoside analogs. Proc Natl Acad Sci USA 1999;96:1492-1497. (Pubitemid 29098478)
10. Harris KS, Brabant W, Styrchak S, et al.: KP-1212/1461, a nucleoside designed for the treatment of HIV by viral mutagenesis. Antiviral Res 2005;67:1-9. (Pubitemid 40798912)
11. Anderson JP, Daifuku R, and Loeb LA: Viral error catastrophe by mutagenic nucleosides. Annu Rev Microbiol 2004;58:183-205. (Pubitemid 39551984)
12. Crotty S, Maag D, Arnold J, et al.: The broad-spectrum antiviral ribonucleoside ribavirin Is an RNA virus mutagen. Nature Med 2000;6:1375-1379. (Pubitemid 32001022)
13. Partiente N, Sierra S, Lowenstein P, and Domingo E: Efficient extinction by combinations of a mutagen and antiviral inhibitors. J Virol 2001;75:9723-9730. (Pubitemid 32900107)
14. Clay PG, McRae MP, and Laurent JP: Safety, tolerability, and pharmacokinetics of KP-1461 in phase I clinical studies: A single oral dose study in non-HIV-infected adults, and a 14-day dose-escalating study in highly antiretroviralexperienced HIV-infected adults. J Int Assoc Physicians AIDS Care 2011;10:232-238.
15. Mullins J, Heath L, Hughes J, et al.: Mutations of HIV-1 genomes in a clinical population treated with the mutagenic nucleoside KP1461. PLoS ONE 2011;6,e15135.