Revisiting monotherapy: heresy or revised orthodoxy?

After the widespread introduction of triple combination antiretroviral therapy in 1996 caused AIDS deaths to plummet, the earlier practice of single-drug treatment--or monotherapy--seemed like an embarrassing phase of medical ignorance. By then, it had become all too apparent that monotherapy promoted the rapid development of drug-resistant virus, often leading to treatment failure. Stories still occasionally surface about an isolated doctor prescribing solo AZT (zidovudine, Retrovir), and many long-time HIV physicians with large practices probably have one or two patients still doing well on two drugs and see no reason to change their regimens. But by and large, hitting hard with two nucleoside reverse transcriptase inhibitors (NRTIs) plus either a protease inhibitor (PI) or a non-NRTI (NNRTI) has become dogma, and is now enshrined in all HIV treatment guidelines.