New HIV Drugs in Development, 2005

Overview

Journal Curr Infect Dis Rep

Specialty Infectious Diseases

Date 2005 Apr 26

PMID 15847725

Authors

Jeffrey P Nadler

Michael C Phillips

Affiliations

Soon will be listed here.

Abstract

Since the introduction of zidovudine 18 years ago, the treatment of HIV has been rapidly evolving. Current therapies target the HIV retrovirus successfully but contain their own perils. Active therapies with reduced adverse effects and long-term activity in the presence of, or reduced susceptibility to, antiviral resistance continue to be needed. Furthermore, more convenient agents that may facilitate adherence to therapy are a goal of new drug development. This review addresses these clinical needs, with a discussion of several new drugs currently in the clinical trial pipeline.

References

Nolan D, Mallal S . Complications associated with NRTI therapy: update on clinical features and possible pathogenic mechanisms. Antivir Ther. 2005; 9(6):849-63. View

Carr A, Samaras K, Burton S, Law M, Freund J, Chisholm D . A syndrome of peripheral lipodystrophy, hyperlipidaemia and insulin resistance in patients receiving HIV protease inhibitors. AIDS. 1998; 12(7):F51-8. DOI: 10.1097/00002030-199807000-00003. View

Mulligan K, Grunfeld C, Tai V, Algren H, Pang M, Chernoff D . Hyperlipidemia and insulin resistance are induced by protease inhibitors independent of changes in body composition in patients with HIV infection. J Acquir Immune Defic Syndr. 2000; 23(1):35-43. DOI: 10.1097/00126334-200001010-00005. View

Miller K, Jones E, Yanovski J, Shankar R, Feuerstein I, Falloon J . Visceral abdominal-fat accumulation associated with use of indinavir. Lancet. 1998; 351(9106):871-5. DOI: 10.1016/S0140-6736(97)11518-5. View

Fikkert V, Van Maele B, Vercammen J, Hantson A, Van Remoortel B, Michiels M . Development of resistance against diketo derivatives of human immunodeficiency virus type 1 by progressive accumulation of integrase mutations. J Virol. 2003; 77(21):11459-70. PMC: 229256. DOI: 10.1128/jvi.77.21.11459-11470.2003. View

Fikkert V, Hombrouck A, Van Remoortel B, De Maeyer M, Pannecouque C, De Clercq E . Multiple mutations in human immunodeficiency virus-1 integrase confer resistance to the clinical trial drug S-1360. AIDS. 2004; 18(15):2019-28. DOI: 10.1097/00002030-200410210-00006. View

Andries K, Azijn H, Thielemans T, Ludovici D, Kukla M, Heeres J . TMC125, a novel next-generation nonnucleoside reverse transcriptase inhibitor active against nonnucleoside reverse transcriptase inhibitor-resistant human immunodeficiency virus type 1. Antimicrob Agents Chemother. 2004; 48(12):4680-6. PMC: 529207. DOI: 10.1128/AAC.48.12.4680-4686.2004. View

Larder B, Hertogs K, Bloor S, van den Eynde C, DeCian W, Wang Y . Tipranavir inhibits broadly protease inhibitor-resistant HIV-1 clinical samples. AIDS. 2000; 14(13):1943-8. DOI: 10.1097/00002030-200009080-00009. View

Deeks S, Smith M, Holodniy M, Kahn J . HIV-1 protease inhibitors. A review for clinicians. JAMA. 1997; 277(2):145-53. View

10.

Squires K . An introduction to nucleoside and nucleotide analogues. Antivir Ther. 2001; 6 Suppl 3:1-14. View

11.

Ben-Romano R, Rudich A, Torok D, Vanounou S, Riesenberg K, Schlaeffer F . Agent and cell-type specificity in the induction of insulin resistance by HIV protease inhibitors. AIDS. 2002; 17(1):23-32. DOI: 10.1097/00002030-200301030-00005. View

12.

Lo J, Mulligan K, Tai V, Algren H, Schambelan M . "Buffalo hump" in men with HIV-1 infection. Lancet. 1998; 351(9106):867-70. DOI: 10.1016/S0140-6736(97)11443-X. View

13.

Goody R, Muller B, Restle T . Factors contributing to the inhibition of HIV reverse transcriptase by chain-terminating nucleotides in vitro and in vivo. FEBS Lett. 1991; 291(1):1-5. DOI: 10.1016/0014-5793(91)81089-q. View

14.

Carr A, Samaras K, Thorisdottir A, Kaufmann G, Chisholm D, Cooper D . Diagnosis, prediction, and natural course of HIV-1 protease-inhibitor-associated lipodystrophy, hyperlipidaemia, and diabetes mellitus: a cohort study. Lancet. 1999; 353(9170):2093-9. DOI: 10.1016/S0140-6736(98)08468-2. View

15.

Furman P, Barry D . Spectrum of antiviral activity and mechanism of action of zidovudine. An overview. Am J Med. 1988; 85(2A):176-81. View

16.

Flexner C . HIV-protease inhibitors. N Engl J Med. 1998; 338(18):1281-92. DOI: 10.1056/NEJM199804303381808. View

17.

Paterson D, Swindells S, Mohr J, BRESTER M, Vergis E, Squier C . Adherence to protease inhibitor therapy and outcomes in patients with HIV infection. Ann Intern Med. 2000; 133(1):21-30. DOI: 10.7326/0003-4819-133-1-200007040-00004. View

18.

Nicholson J, Browning S, Hengel R, Lew E, Gallagher L, Rimland D . CCR5 and CXCR4 expression on memory and naive T cells in HIV-1 infection and response to highly active antiretroviral therapy. J Acquir Immune Defic Syndr. 2001; 27(2):105-15. DOI: 10.1097/00126334-200106010-00002. View

19.

Gewurz B, Jacobs M, Proper J, Dahl T, Fujiwara T, Dezube B . Capravirine, a nonnucleoside reverse-transcriptase inhibitor in patients infected with HIV-1: a phase 1 study. J Infect Dis. 2004; 190(11):1957-61. DOI: 10.1086/425581. View

20.

Gotte M, Wainberg M . Biochemical mechanisms involved in overcoming HIV resistance to nucleoside inhibitors of reverse transcriptase. Drug Resist Updat. 2001; 3(1):30-38. DOI: 10.1054/drup.2000.0126. View