Human immunodeficiency virus drug resistance

Johnston E, Winters MA, Rhee SY, Merigan TC, Schiffer CA, Shafer RW (2004) Association of a novel human immunodeficiency virus type 1 protease substrate cleft mutation, L23I, with protease inhibitor therapy and in vitro drug resistance. Antimicrob Agents Chemother 48 4864 868... 

In this chapter we describe the current insights into the evolution of viruses under pressure of antiviral therapy and the potential impact on viral fimess. As most recent work in this field has been done in the field of human immunodeficiency virus (HIV), we use the evolution of this virus as the basis for the chapter. Subsequently, we describe resistance evolution for Hepatitis B virus (HBV), where large progress has been made in recent years. Furthermore, we describe the resistance development for Hepatitis C virus (HCV), for which a very active drug development program is undertaken by several pharmaceutical companies. Finally, we discuss resistance evolution for Influenza. 

Hertogs K, de Bethune MP, Miller V, Ivens T, Schel P, Van Cauwenberge A, Van Den Eynde C, Van Gerwen V, Azijn H, Van Houtte M, Peelers F, Staszewski S, Conant M, Bloor S, Kemp S, Larder B, Pauwels R (1998) A rapid method for simultaneous detection of phenotypic resistance to inhibitors of protease and reverse transcriptase in recombinant human immunodeficiency virus type 1 isolates from patients treated with antiretroviral drugs. Antimicrob Agents Chemother 42 269-276... 

Najera I, Richman DD, Olivares I, Rojas JM, Peinado MA, Perucho M, Najera R, Lopez GaHndez C (1994) Natural occurrence of drug resistance mutations in the reverse transcriptase of human immunodeficiency virus type 1 isolates. AIDS Res Hum Retroviruses 10 1479-1488 Nijhuis M, Boucher CAB, Schipper R Leitner T, Schuurman R, Albert J (1998) Stochastic processes strongly influence HIV-1 evolution during suboptimal protease inhibitor therapy. Proc Natl Acad Sci USA 95 14441-14446... 

HIV phenotype A type of resistance testing for human immunodeficiency virus (HIV) in which a patient s blood sample is obtained, and the patient s HIV genes that encode for reverse transcriptase and protease are removed and placed in an HIV viral vector. This viral vector is replicated in a cell culture system with varying concentrations of antiretrovirals. A drug concentration-viral inhibition curve is developed and the concentration needed to inhibit 50% of the patient s virus is reported. This is used to predict resistance versus susceptibility. 

Balzarini J, Karlsson A, De Clercq E. Human immunodeficiency virus typel drug-resistance patterns with different l-[(2-hydroxyethoxy)methyl]-6-(phe-nylthio)thyminc derivatives. Mol Pharmacol 1993 44 694-701. 

Balzarini J, Karlsson A, Perez-Perez M-J, Camarasa M-J, Tarpley WG, De Clercq E. Treatment of human immunodeficiency virus type 1 (HlV-l)-in-fected cells with combinations of HIV-l-specific inhibitors results in a different resistance pattern than does treatment with single-drug therapy. J Virol 1993 67 5353-5359. 

Boyer PL, Ding J, Arnold E, Hughes SH. Drug resistance of human immunodeficiency virus type 1 reverse transcriptase subunit specificity of mutations that confer resistance to nonnucleoside inhibitors. Antimicrob Agents Chemother 1994 38 1909-1914. 

Shafer RW, Kozal MI, Winters M, Iversen AKN, Katenstein DA, Ragni MV, et al. Combination therapy with zidovudine and didanosine selects for drug-resistant human immunodeficiency virus type 1 strains with unique patterns of pol gene mutations. J Infect Dis 1994 169 722-729. 

The human immunodeficiency virus (HIV) is one of only a few retroviruses known to infect humans. It is estimated that approximately twenty-two million people are now infected worldwide [1]. With only a tiny number of exceptions, infection ultimately leads to the development of the lethal condition of acquired immunodeficiency syndrome, or AIDS. To date, only a handful of drugs have been shown to have any effect on the course of the disease. These are, in general, relatively ineffective at significantly prolonging life, and drug resistance develops rapidly. Equally discouraging, vaccines have not yet been developed to prevent infection. 

Boyer PL, Currens MJ, McMahon JB, Boyd MR, Hughes SH. Analysis of nonnucleoside drug-resistant variants of human immunodeficiency virus type 1 reverse transcriptase. J Virol 1993 67 2412-2420. 

Efavirenz (DMP 266) (1) is an effective non-nucleoside inhibitor of reverse transcriptase of the human immunodeficiency virus (HIV) recently registered by the US Food Drug Administration (FDA) for treatment of the acquired immunodeficiency syndrome (AIDS).1 2 3 Inhibition of HIV reverse transcriptase by nucleosides like azidothymidine (AZT) (2) is a proven therapy for delaying the progression to AIDS. However, the rapid viral mutation to resistant strains requires the development of new therapeutic agents. The recent development of both protease inhibitors and non-nucleoside reverse transcriptase inhibitors offers hope of effective treatment especially when coadministered. 

Labrosse, B. Pleskoff, O. Sol, N. Jones, C. Henin, Y AUzon, M. Resistance to a drug blocking human immunodeficiency virus type 1 entry (RPR103611) is conferred by mutations in gp41. J. Virol, 1997, 71 8230-8236. 

Driscoll, J. S., Mayers, D. L., Bader, J. P., et al. (1997) 2 -I hioro-2, 3 -dideoxyarabinosylade-nine (F-ddA) activity against drug-resistant human immunodeficiency virus strains and clades A-E. Antivir. Chem. Chemother., 8, 107-111. 

Kaye, S., Loveday, C., and Tedder R. S. (1992) A microtitre format point mutaion assay Application to the detection of drug resistance in human immunodeficiency virus type-1 infected patients treadted with zidovudine. J. Med. Virol. 37,241-246. 

Schmit, J.-C., Cogniaux, J., Hermans, P Van Vaeck, C., Sprecher, S Van Remoortel, B., Witvrouw, M Balzarini, J., Desmyter, J., De Clercq, E., and Vandamme, A.-M. (1996) Multiple drug resistance to nucleoside analogues and nonnucleoside reverse transcriptase inhibitors in an efficiently replicating human immunodeficiency virus type 1 patient strain../. Infect. Dis. 174,962-968. 

Hirsch MS, Brun-Vezinet F, Clotet B, Conway B, Kuritzkes DR, D Aquda RT, et al. Antiretroviral drug resistance testing in adults with human immunodeficiency virus type 1 2003 recommendations of an international AIDS Society-USA panel. Chn Infect Dis 2003 37 113-28. 

AIDS (Acquired Immuno Deficiency Syndrome) poses a threat to India as a large number of people are infected with HTV (Human Immunodeficiency Virus). There are no drugs today for AIDS. The problem which has dogged anti- HIV drugs is that resistant mutant forms of virus are formed within mere weeks. Lot of research work is to be done in search of a vaccine against HIV. 

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