Prospects for drug treatment of AIDS

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The first recognized cases of the acquired immune deficiency syndrome (AIDS) occurred in the summer of 1981 in America. Human immunodeficiency virus (HIV) was discovered by Barre-Sinoussi, Montgnier and colleagues at the institute Pasteur Paris 1983. HIV-1 and HIV-2, the major and minor human AIDS viruses, are transmitted in ways that are typical for all retroviruses- 'vertically', that is from mother to infant, and 'horizontally' through sexual intercourse and through infected blood. Infection with HIV causes a spectrum of clinical problems beginning at the time of serconversion and terminating with AIDS and death. Various potential targets for antiviral treatment have been identified since we have gained a better understanding of the replicative cycle and molecular biology of HIV. The first drugs made available for clinical use were inhibitors of the reverse transcriptase enzyme (RT). RT inhibitors include nucleoside analogues that inhibit by chain termination and competitive inhibition of the enzyme and non-nucleoside agents which bind directly to RT and are non-competitive inhibitors. More recently, specific inhibitors of the HIV protease and integrase enzymes have been evaluated and introduced into clinical use. HIV replication from its integrated site is controlled by a number of regulatory genes. The tat (transactivating transcription) gene codes for a protein that transactivates the promoter in the HIV long terminal repeat (LTR) region which amplifies viral transcription. Tat inhibitors are under clinical investigation. Regarding HIV vaccines, novel approaches are being tried. Chemoprophylaxis against pneumocystis carinii pneumonia, which remains the most serious opportunistic infection, continues to be recommended as the standard care for HIV-infected person with CD4 counts of less than 200/μl. Guidelines for managing HIV infection include regular monitoring of IIIV-1 plasma RNA (viral load) and the use of triple antiretroviral drug combination. Development of antiviral therapy aimed at other parts of the viral replication cycle is urgently needed.

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