Investigational HIV integrase inhibitors in phase I and phase II clinical trials

References

• Engelman A, Kessl JJ, Kvaratskhelia M. Allosteric inhibition of HIV-1 integrase activity. Curr Opin Chem Biol. 2013 Jun;17(3):339–345.
   PubMed Web of Science ®Google Scholar
• Feng L, Larue RC, Slaughter A, et al. HIV-1 integrase multimerization as a therapeutic target. Curr Top Microbiol Immunol. 2015;389:93–119.
   PubMed Web of Science ®Google Scholar
• Weydert C, De Rijck J, Christ F, et al. Targeting virus-host interactions of HIV replication. Curr Top Med Chem. 2016;16(10):1167–1190.
   PubMed Web of Science ®Google Scholar
• Park TE, Mohamed A, Kalabalik J, et al. Review of integrase strand transfer inhibitors for the treatment of human immunodeficiency virus infection. Expert Rev Anti Infect Ther. 2015;13(10):1195–1212.
   PubMed Web of Science ®Google Scholar
• Elliot E, Chirwa M, Boffito M. How recent findings on the pharmacokinetics and pharmacodynamics of integrase inhibitors can inform clinical use. Curr Opin Infect Dis. 2017 Feb;30(1):58–73.
   PubMed Web of Science ®Google Scholar
• Grobler JA, Hazuda DJ. Resistance to HIV integrase strand transfer inhibitors: in vitro findings and clinical consequences. Curr Opin Virol. 2014 Aug 13;8c:98–103.
   Web of Science ®Google Scholar
• Mesplede T, Wainberg MA. Resistance against integrase strand transfer inhibitors and relevance to HIV persistence. Viruses. 2015 Jul 07;7(7):3703–3718.
   PubMed Web of Science ®Google Scholar
• Trezza C, Ford SL, Spreen W, et al. Formulation and pharmacology of long-acting cabotegravir. Curr Opin HIV AIDS. 2015 Jul;10(4):239–245.
   PubMed Web of Science ®Google Scholar
• Han YS, Mesplede T, Wainberg MA. CABOTEGRAVIR. Drugs Future. 2015;40(11):705–715.
   Web of Science ®Google Scholar
• Whitfield T, Torkington A, van Halsema C. Profile of cabotegravir and its potential in the treatment and prevention of HIV-1 infection: evidence to date. Hiv/Aids. 2016;8:157–164.
   Google Scholar
• Landovitz RJ, Kofron R, McCauley M. The promise and pitfalls of long-acting injectable agents for HIV prevention. Curr Opin HIV AIDS. 2016 Jan;11(1):122–128.
   PubMed Web of Science ®Google Scholar
• Spreen W, Ford SL, Chen S, et al. GSK1265744 pharmacokinetics in plasma and tissue after single-dose long-acting injectable administration in healthy subjects. J Acquir Immune Defic Syndr. 2014 Dec 15;67(5):481–486.
   PubMed Web of Science ®Google Scholar
• Reese MJ, Bowers GD, Humphreys JE, et al. Drug interaction profile of the HIV integrase inhibitor cabotegravir: assessment from in vitro studies and a clinical investigation with midazolam. Xenobiotica. 2016;46(5):445–456.
   PubMed Web of Science ®Google Scholar
• Ford S Rifampin (RIF) decreases cabotegravir (CAB) exposure following oral coadministration. 17th International Workshop on Clinical Pharmacology of HIV and Hepatitis Therapy. Reviews in Antiviral Therapy & Infectious Diseases. 2016;Jun 8–10, 2016, Washington (DC).
   Google Scholar
• Ford SL, Gould E, Chen S, et al. Lack of pharmacokinetic interaction between rilpivirine and integrase inhibitors dolutegravir and GSK1265744. Antimicrob Agents Chemother. 2013 Nov;57(11):5472–5477.
   PubMed Web of Science ®Google Scholar
• Spreen W, Williams P, Margolis D, et al. Pharmacokinetics, safety, and tolerability with repeat doses of GSK1265744 and rilpivirine (TMC278) long-acting nanosuspensions in healthy adults. J Acquir Immune Defic Syndr. 2014 Dec 15;67(5):487–492.
   PubMed Web of Science ®Google Scholar
• Spreen W, Min S, Ford SL, et al. Pharmacokinetics, safety, and monotherapy antiviral activity of GSK1265744, an HIV integrase strand transfer inhibitor. HIV Clin Trials. 2013 Sep–Oct;14(5):192–203.
   PubMed Web of Science ®Google Scholar
• Margolis DA, Brinson CC, Smith GH, et al. Cabotegravir plus rilpivirine, once a day, after induction with cabotegravir plus nucleoside reverse transcriptase inhibitors in antiretroviral-naive adults with HIV-1 infection (LATTE): a randomised, phase 2b, dose-ranging trial. Lancet Infect Dis. 2015 Oct;15(10):1145–1155.
   PubMed Web of Science ®Google Scholar
• Margolis D, et al. Cabotegravir + rilpivirine as long-acting maintenance therapy: LATTE-2 week 48 results. AIDS 2016 2016;2016 Jul 18–22, Durban. J Int AIDS Soc. Orallate breaker abstract THAB0206LB.
   Google Scholar
• Margolis D, et al. Cabotegravir+rilpivirine as long-acting maintenance therapy: LATTE-2 week 32 results. 23rd CROI 2016;2016 Feb 22–25, Boston. Oral late breaker abstract 31LB.
   Google Scholar
• Andrews CD, Heneine W. Cabotegravir long-acting for HIV-1 prevention. Curr Opin HIV AIDS. 2015 Jul;10(4):258–263.
   PubMed Web of Science ®Google Scholar
• Andrews CD, Yueh YL, Spreen WR, et al. A long-acting integrase inhibitor protects female macaques from repeated high-dose intravaginal SHIV challenge. Sci Transl Med. 2015 Jan 14;7(270):270ra4.
   PubMed Web of Science ®Google Scholar
• Radzio J, Spreen W, Yueh YL, et al. The long-acting integrase inhibitor GSK744 protects macaques from repeated intravaginal SHIV challenge. Sci Transl Med. 2015 Jan 14;7(270):270ra5.
   PubMed Web of Science ®Google Scholar
• Markowitz M, FrankI I, Grant R ECLAIR: phase 2A safety and PK study of cabotegravir LA in HIV-uninfected men. CROI 2016;2016 Feb 22–25, Boston. Abstract 106.
   Google Scholar
• Jessica R, Olivia C, Mian-er C, et al. Resistance emerence in macaques administered cabotegravir LA during acute infection. CROI 2017 2017;February 13–16, 2017, Seattle, Absctract #84.
   Google Scholar
• Tsiang M, Jones GS, Goldsmith J, et al. Antiviral activity of bictegravir (GS-9883), a novel potent HIV-1 integrase strand transfer inhibitor with an improved resistance profile. Antimicrob Agents Chemother. 2016 Dec;60(12):7086–7097.
   PubMed Web of Science ®Google Scholar
• Gallant JE, Thompson M, DeJesus E, et al. Antiviral activity, safety, and pharmacokinetics of bictegravir as 10-day monotherapy in HIV-1-infected adults. J Acquir Immune Defic Syndr. 2017 Feb 08;75:61–66.
   PubMed Web of Science ®Google Scholar
• Sax PE, DeJesus E, Crofoot G, et al. Bictegravir versus dolutegravir, each with emtricitabine and tenofovir alafenamide, for initial treatment of HIV-1 infection: a randomised, double-blind, phase 2 trial. The Lancet HIV. 2017 Feb 14. doi: 10.1016/S0140-6736(17)32299-7.
   Web of Science ®Google Scholar
• Zhang H Clinical pharmacology of the HIV integrase strand transfer inhibitor bictegravir. CROI 2017. Seattle, abstract 40, 2017.
   Google Scholar
• Fader LD, Malenfant E, Parisien M, et al. Discovery of BI 224436, a Noncatalytic Site Integrase Inhibitor (NCINI) of HIV-1. ACS Med Chem Lett. 2014 Apr 10;5(4):422–427.
   PubMed Web of Science ®Google Scholar
• Christ F, Voet A, Marchand A, et al. Rational design of small-molecule inhibitors of the LEDGF/p75-integrase interaction and HIV replication. Nat Chem Biol. 2010 Jun;6(6):442–448.
   PubMed Web of Science ®Google Scholar
• Beck-Engeser GB, Eilat D, Harrer T, et al. Early onset of autoimmune disease by the retroviral integrase inhibitor raltegravir. Proc Natl Acad Sci U S A. 2009 Dec 08;106(49):20865–20870.
   PubMed Web of Science ®Google Scholar
• Koh Y, Matreyek KA, Engelman A. Differential sensitivities of retroviruses to integrase strand transfer inhibitors. J Virol. 2011 Apr;85(7):3677–3682.
   PubMed Web of Science ®Google Scholar
• Fenwick C, Amad M, Bailey MD, et al. Preclinical profile of BI 224436, a novel HIV-1 non-catalytic-site integrase inhibitor. Antimicrob Agents Chemother. 2014 Jun;58(6):3233–3244.
   PubMed Web of Science ®Google Scholar
• Mesplede T, Quashie PK, Zanichelli V, et al. Integrase strand transfer inhibitors in the management of HIV-positive individuals. Ann Med. 2014 May;46(3):123–129.
   PubMed Web of Science ®Google Scholar
• Raffi F, Esser S, Nunnari G, et al. Switching regimens in virologically suppressed HIV-1-infected patients: evidence base and rationale for integrase strand transfer inhibitor (INSTI)-containing regimens. HIV Med. 2016 Oct;17(Suppl 5):3–16.
   PubMed Web of Science ®Google Scholar