In the late 1980s, Sonnabend became a prominent critic of the use of AZT monotherapy to treat asymptomatic, HIV-positive people, which he thought was based on insufficient clinical evidence. Nevertheless, he did prescribe the drug in short courses for people with indications of elevated interferon, which he believed might play an important role in pathogenesis and could be controlled by AZT. In 2006 he expressed his view that high doses of AZT had "killed thousands" during the late 1980s and early 1990s.