ISSUES IN COMBINATION ANTIRETROVIRAL THERAPY - A REVIEW

High viral burden and replication persist during all phases of human i mmunodeficiency virus (HIV) disease. Although monotherapy has yielded considerable benefits, these benefits are neither absolute nor durable . Combination therapy has multiple goals: to reduce Viral replication and burden; to relieve drug toxicity; to attenuate viral mutations lea ding to resistance and possibly to conversion from non-syncytium-induc ing to syncytium-inducing virus; and to broaden the spectrum of specif ic cells and tissues in which antiretroviral agents are active. At pre sent, zidovudine remains the cornerstone of antiretroviral monotherapy and combination therapy. A partial list of agents tried in combinatio ns with and without zidovudine includes the nucleoside analogues zalci tabine and didanosine; non-nucleoside reverse-transcriptase inhibitors (nevirapine, delavirdine, atevirdine, pyridinones, TIBO derivatives); protease inhibitors; inhibitors of viral regulatory functions (tat in hibitors); cy tokine antagonists; acyclovir; and colony-stimulating fa ctors. The rationales, the regimens, and the results all vary. We usua lly recommend combination therapy for treatment-naive patients who are asymptomatic with <200 CD4(+) cells/mm(3) or who are symptomatic, and for patients who have been receiving zidovudine monotherapy and who a re stable but whose CD4(+) counts have fallen to <300 cells/mm(3), or who are progressing. In the absence of definitive results from clinica l trials of combination therapy, the decision to embark on this route remains to be made between each individual patient and the practitione r.