Anti-HIV drug development--an overview.

Highly active antiretroviral therapy (HAART) has markedly decreased mortality and morbidity in the developed world. HAART consists of a combination of three or more of the following classes of antiretroviral (ARV) drug: reverse transcriptase inhibitors, protease inhibitors and a recently approved fusion inhibitor. However, HAART cannot completely eradicate HIV from the body, results in long-term toxicity and eventually leads to the emergence of drug-resistant HIV strains. These problems prompt the search for potent new drugs that are active against drug-resistant viral strains and that can safely be combined with other ARV drugs. The aim of this review was to give an overview of new compounds in preclinical or early clinical development that interact with various steps in the HIV life cycle: virus-cell attachment; gp120-CD4 binding; gp120-coreceptor binding; viral fusion; viral assembly and disassembly; reverse transcription; nuclear import of the pre-integration complex; proviral integration; viral transcription; processing of viral transcripts and nuclear export; assembly of new virions; cellular factors involved in HIV replication.