There are, however, some significant practical and theoretical difficulties with available antiretroviral agents. Although mortality and frequency of opportunistic infections are reduced in patients taking zidovudine, a complete and sustained improvement in immune status has not been achieved (13, 14). In addition, frequent toxic effects prevent many individuals from tolerating these drugs for extended periods (15). Recent in vitro evidence of retroviral resistance has also been presented, although the clinical importance of this is as yet unknown (16). In hopes of increasing efficacy and reducing toxicity, studies are now underway examining the potential role of combination therapies for HIV infection. Such approaches include combined therapy with two or more agents from the same class (eg, reverse transcriptase inhibitors) or from distinct classes with different mechanisms of action (eg, RT inhibitors plus immunomodulators). Despite the major advances in treating HIV disease that have occurred in the past five years, it is clear that the need is still great for more efficacious, less toxic therapies with novel mechanisms of action.