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HIV Entry Inhibitors: Current Status
1119-1125
Correspondence
E.mail:lekhasaha@rediffmail.com
Current therapeutic intervention in HIV infection relies upon 20 different drugs. Despite the impressive efficacy shown by these drugs, we are confronted with an unexpected frequency of adverse effects such as mitochondrial toxicity, lipodystrophy and resistance, not only to individual drugs, but to entire drug classes. Thus, there is now a great need for new antiretroviral drugs with reduced toxicity, increased activity against drug-resistant viruses and a greater capacity to reach tissue sanctuaries of the virus. Two different HIV molecules have been selected as targets of drug inhibition so far: reverse transcriptase and protease. Drugs that target the interactions between the HIV envelope and the cellular receptor complex are a `new entry’ into the scenario of HIV therapy, and have recently raised great interest because of their activity against multi-drug resistant viruses.
There are several compounds that are at different developmental stages in the pipeline to counter HIV entry(Table/Fig 2), some of which include:
i) the attachment inhibitor dextrin – 2 – sulfate;
ii) the inhibitors of the glycoprotein (gp) 120/CD4 interaction PRO 542, TNX 355 and BMS 488043;
iii) the co-receptor inhibitors subdivided in those targeting CCR5 and those targeting CXCR4 and
iv) fusion inhibitors enfuvirtide (T-20) and tifuvirtide (T-1249).