Combination therapy: more effective control of HIV type 1?

The rationale for combining anti-HIV-1 agents is to provide more complete viral suppression, to limit the emergence of drug resistance during chronic viral replication, and to provide more effective antiretroviral treatment even when mixtures of drug-resistant and drug-sensitive strains are present. In vitro experiments reveal increased suppression with multiple-drug therapy, but viral breakthrough occurs after prolonged time in culture even during triple-drug therapy. Clinical results available to date indicate that drugs should be given simultaneously for optimal benefit. There appears to be a rationale for early initiation of combination therapy before the onset of increased viral burden and the emergence of syncytium-inducing viral variants. The results of ACTG protocol 155 revealed benefit of zidovudine and zalcitabine over monotherapy with either agent in patients with CD4+ cell counts > or = 150 cells/mm3. However, further clinical studies will be necessary before firm recommendations can be made about the indications for combination antiretroviral therapy in HIV-1-infected individuals at different stages of disease. Ultimately, we need better drugs, in combination, which significantly impact on HIV-1 burden to achieve more complete viral suppression and to reduce selection of drug-resistant viral variants.