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Conference
"Multiple Failure" Dr. Julio Montaner (biography) English - 2002-04-14 - 53 minutes
Summary : Triple drug therapy has led to a dramatic decrease in morbidity and mortality associated with infection by the Human Immunodeficiency Virus (HIV). Despite this, we continue to see substantial rates of virological failure. Given our understanding of the physiopathology of HIV disease, it is clear that this will lead to eventual CD4 decline and disease progression over a period of months to years. Every effort should therefore be made to try to abort this sequence of events. Rates of treatment failure are anywhere between 10-50% at one year after initiation of the first course of triple drug therapy.
It is now clear that rates of failure accelerate with successive rounds of treatment. The issue is aggravated by the presence of co-morbidities, such as HCV. Furthermore, the pre-existence of HIV resistance to antiretroviral therapies whether through primary resistance or acquired resistance, in the case of pre-treated patients, further aggravates this issue. Over recent years, we have become aware of the contribution of resistance testing to optimize the selection of antiretroviral agents. This is particularly useful in second and third line therapy. Unfortunately, the role of resistance testing is limited in patients with multiple failures because of the relatively limited menu of options available in terms of alternative drugs. More recently, we have been able to incorporate pharmacokinetic measurements to the evaluation of multiple drug rescue therapy. When taken together, pharmacokinetic profiles in combination with resistance testing allow for better characterization of the potential contribution of the given agent. While these concepts are certainly contributing greatly to the management of one and two class failures, things become increasingly difficult as patients present with three class failure and with high levels of resistance to all agents. Multiple drug rescue therapy has evolved as an important interim measure to prevent disease progression as well as further evolution of resistance. MDRT regimens have evolved over the last several years becoming more acceptable and better tolerater. Fortunately, new agents are coming to the front to assist in this task. Among them, T20, tenofovir, tipranavir, and the TMC line of compounds appear to be highly promising in this regard. As in other settings, physician experience and patient's adherence should be regarded as critically important in optimizing therapeutic response.
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