Purpose. A case of probable interaction of levothyroxine and ritonavir is presented along with a review of the relevant literature and recommendations on clinical management. Summary. A 37-year-old woman with human immunodeficiency virus infection who had recently undergone thyroidectomy for a benign multinodular goiter presented to a clinic with hypothyroidism (she was also found to be pregnant), and treatment with levothyroxine 75 mu g daily was initiated. While receiving antiretroviral therapy (abacavir-lamivudine and lopinavir-ritonavir) during pregnancy, the patient had persistently elevated serum thyroid-stimulating hormone (TSH) concentrations (up to 125.89 mu lU/mL) despite gradual escalation of the levothyroxine dosage to 175 mu g daily. An interaction between ritonavir and levothyroxine was suspected, and dolutegravir was substituted for lopinavir-ritonavir. Within 4 months, the TSH concentration had normalized. The daily levothyroxine dose was tapered over a 5-month period and stabilized at 125 mu g, and TSH concentrations remained within the normal range over an 18-month follow-up period. Scoring of the case using the Drug Interaction Probability Scale yielded a score of 6 out of 11, indicating a probable interaction between levothyroxine and ritonavir. A literature search identified 4 reported cases of interactions involving levothyroxine and ritonavir. Conclusion. A potentially serious and underrecognized drug interaction between ritonavir and levothyroxine was observed in a pregnant woman with postthyroidectomy-related hypothyroidism. This case and a review of other cases reported in the literature indicate that higher-than-usual doses of levothyroxine may be required in patients who are taking ritonavir concurrently.