Human immunodeficiency virus drug-resistant strains

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. 

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. 

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. 

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. 

The human immunodeficiency virus (HIV), the virus that causes AIDS, has proven to be among the most incurable foes ever faced by modern medical science. One reason for this is the virus s remarkable ability to adapt. Resistant strains of the virus appear quickly, rendering obsolete the newest and most powerful AIDS drugs. Now some researchers are using the virus s adaptability as a way to fight it. 

A first application of the new, very efficient asymmetric synthesis of C2-sym-fnetric ketones is described in scheme 7. Since the Center for Disease Control in Atlanta (USA) defined the diagnostic term AIDS (Acquired Immunodeficiency Syndrome) in 1982 [24] only three medications have been authorized for treatment of AIDS 3 -azido-3 -deoxythymidine (AZT, Wellcome, 1987), 2 ,3 -dideoxyinosine (DDI, Bristol Myers Squibb, 1992), and 2 ,3 -dideoxycytosine (DDC, Hoffmann La Roche, 1992), which was recently introduced for limited use. These drugs inhibit the enzyme reverse transcriptase of the human immunodeficiency virus (HIV). Nevertheless, they are only able to prolong somewhat the survival of patients with advanced cases of AIDS. They also lead to considerable side-effects (bone marrow damage, neuropathy) and to the generation of more resistant strains of the virus [25]. 

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