Combination therapy for HIV: towards long term control of disease progression

The difficulty of curing HIV patients with currently available agents has now been demonstrated and the model of care has returned to the long-term use of antiretroviral therapy. As such, the current minimum standard of care is triple drug therapy, with two nucleoside analogues,along with either a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor (NNRT). Such regimens induce long-term virologic suppression in only 50 - 67% cases, so new approaches are needed. The most promising of these includes the use of two protease inhibitors,particularly in drug-naive patients, with the addition of one or two nucleoside analogues. Newer agents that merit further study include hydroxyurea,abacavir, adefovir, amprenavir and efavirenz. Their role in clinical practice remains to be defined. More complex regimens (including six drugs) are also under consideration. Although they may be more effective, long-term adherence to therapy may be problematic, and such approaches may be more appropriate for short-term use to 'induce' a virologic remission that could then be 'maintained' using a much simpler regimen. Preliminary data generated using such an approach have been disappointing, but this may relate to the specific selection of patients and regimens rather than a basic conceptual flaw with the approach itself. Although much progress has been made in the field of antiretroviral therapy, there is still a long way to go. The insightful study of new combinations of older and newer agents will help us to get closer to our goal of long-term control of HIV infection in all patients.