Patients who have never taken antiretroviral agents respond better than those with prior antiretroviral experience. Patients with higher CD4 cell counts respond better than those with lower CD4 cell counts. The lower the nadir of the response in viral load, the better the chance for durability of the regimen. Adding 2 potent drugs concurrently is superior to adding the drugs sequentially. Results were better in patients who had indinavir and lamivudine added to zidovudine at the same time than in patients who had the drugs added one at a time over a period of months.
Adherence is crucial to achieving the benefits of antiretroviral regimens.
The initial, concurrently introduced, potent antiretroviral regimen has the best chance for a durable effect if patient adherence can be maintained. If a sustained reduction in viral load is not achieved, drug resistance will develop, with potential cross-resistance to other agents. Similarly, cross-resistance among the protease inhibitors may be significant. Such studies will be challenging to perform and more difficult to assess than simple short-term drug efficacy studies. As antiretroviral regimens succeed in reducing viral load levels to the limits of assay detection in a majority of patients, regimens increasingly will be distinguished by properties of easy long-term adherence.