Trials That Matter: CD4⁺ T-Lymphocyte Count–Guided Interruption of Antiretroviral Therapy in HIV-Infected Patients

Editor's Note:We are deeply sorry to report that Dr. Abrutyn died unexpectedly while preparing this editorial for publication. He was an associate editor of Annals for 29 years, which is just one of many accomplishments of a splendid life in medicine. An appreciation of his career appears elsewhere in this issue.

Advances in antiretroviral chemotherapy have been remarkably successful in suppressing HIV replication, preventing or reversing much of the immunologic damage from HIV infection, reducing the incidence of clinical events and hospitalizations, and prolonging life (1). However, treatment is merely suppressive, not curative (2), and antiretroviral therapy is associated with clinical toxicity, emergence of drug resistance, substantial cost, and burdensome pill-taking. As a result, the concept of structured interruptions to treatment is attractive. Proponents of structured treatment interruption have had several theoretical goals, including providing pulse exposures of viral antigens as an autoimmunization strategy to boost anti-HIV immune responses (3–5); repopulating with drug-sensitive “wild-type” virus in persons with multidrug-resistant HIV (6–9); and reducing drug exposure and its adverse clinical, social, and economic consequences (10–12).

Current treatment guidelines recommend waiting until an AIDS-defining clinical event has occurred or the patient's CD4⁺ T-lymphocyte count (CD4 count) has fallen below 200 cells/mm³, signifying that the patient is substantially immunocompromised, before starting …