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The gains made in HIV-1 antiretroviral therapy (ART) have been substantial. Despite these gains new therapies for HIV-1 infection are needed. In the clinical setting only 30-70% of infected individuals achieve the desired response to treatment. Therapeutic agents that are more potent, achieve high concentrations and/or are directed at new targets may help improve rates of response. However now and in the near future treatment failure will remain common. Many factors may contribute to treatment failure including drug tolerability and toxicity, adherence to treatment and emergence of HIV-1 resistance. Agents with improved pharmacokinetics requiring fewer pills and doses may lessen treatment failure or improve response to subsequent regimens by making long-term adherence to treatment easier. Short-term and long-term toxicities of our current regimens continue to be recognized and new agents that limit toxicity and improve tolerability will strengthen therapeutic options. Finally HIV-1 resistance to available reverse transcriptase (RT) and protease inhibitors has become extremely common, not only because of selection for resistance on therapy but also due to transmission of resistant variants. Resistance is likely to be the final common pathway in prolonged or recurrent treatment failure. Agents that address one or more of these treatment failure factors are currently in development. These agents can be divided into 2 general categories 1) new agents that target HIV-1 enzymes for which therapies are currently available and 2) agents that inhibit HIV-1 at new targets with in its life cycle. New agents in each of the existing ART categories, nucleoside RTI, non-nucleoside RTI and protease inhibitors, which improve pharmacokinetics or have increased activity against resistant HIV-1 or both, are in development. Examples of these agents will be discussed. Alternative targets for the inhibition of HIV-1 have been identified such as virus cell surface interaction and HIV integrase and agents that target these sites are likely to be active against PI and RTI resistance HIV-1. Inhibitors of HIV-1 fusion have reached clinical trials. CXCR-4 and CCR-5 inhibitors with in vitro activity are in early development. Inhibitors of HIV-1 integrase have been identified and development is anxiously awaited. |
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© 7th
Conference on Retroviruses and Opportunistic Infections, |