Future agents
For the reasons of poor tolerability, suboptimal antiviral potency and long-term drug toxicity, it is important that new antiretroviral agents and therapeutic strategies are developed and evaluated.
New formulations of current drugs which improve tolerability and reduce pill burden will help to improve adherence in patients. New protease and reverse transcriptase inhibitors are currently undergoing clinical trials which in vitro appear to be effective against viral isolates which are resistant to different drugs. Whether these agents will prove to be clinically effective will be important in treating those patients who have previously failed combination therapies.New classes of drugs are also being developed. Fusion inhibitors which block the activity of the GP41 viral transmembrane protein are in Phase III clinical trials and are likely to be the first new class of drug to reach the bedside.
As well as specific drugs that inhibit targets in the viral replication cycle, immunotherapeutic approaches are so being assessed. Treatment with cycles of the cytokine interleukin 2 results in substantial increase in CD4 counts but has little effect on plasma viral load levels. Interleukin 2 may also improve immune responses to HIV and a large randomised international trial is underway to assess its efficacy in combination with effective antiretroviral combination regimens. Therapeutic vaccines are also under evaluation which might improve specific immune responses and assist immunological control of HIV replication. Their clinical effectiveness remains uncertain.
Few areas of medicine have seen such dramatic changes in treatment with a resulting reduction in morbidity and mortality as there has been in patients with HIV infection. It is very likely that therapeutic options will continue to improve, although the long-term efficacy of treatment over many years still remains uncertain.
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