Orogastric administration of crushed darunavir tablets for a critically ill patient.

Abstract

When HIV-positive patients are critically ill and unable to take medications orally, administration of highly active antiretroviral therapy (HAART) becomes challenging. The foremost issue is the lack of parenteral formulations and oral suspensions. Only limited clinical evidence directly addresses the conversion of antiretroviral drugs from the oral to the enteral route. Interruption of HAART is not an acceptable alternative, as this results in HIV viral rebound, immunodeficiency, opportunistic infections, and development of resistance to antiretroviral treatment. Altering the route of administration may affect the plasma concentration of antiretrovirals, which also affects clinical outcomes. For example, as described in one case report, a 28-year-old HIV-positive man with diffuse large B cell–type lymphoma of the duodenum was taking the liquid or powder formulations of lopinavir–ritonavir, abacavir, and lamivudine (at standard adult doses) by oral ingestion, with suppression of the viral load to less than 400 copies/mL. Development of a duodenal obstruction necessitated insertion of a percutaneous jejunal feeding tube (located ≥ 35 cm distal to the ligament of Treitz). HAART was reinitiated via the jejunostomy, leading to HIV viral rebound (to 11 000 copies/mL), undetectable serum concentration of lopinavir, and development of resistance to lamivudine (M184V mutation). Gastric bypass surgery was performed to connect the gastric corpus to the jejunum (20 cm distal from the ligament of Treitz). HAART, including lopinavir–ritonavir (oral liquid), abacavir, and tenofovir, was restarted, and measurement of serum lopinavir concentration 18 weeks later demonstrated adequate absorption of the medication, with HIV viral suppression (to 52 copies/mL). Darunavir is an HIV-1 protease inhibitor recommended for combination HAART regimens for both treatment-naive and treatment-experienced patients. This antiretroviral agent must be administered with ritonavir and food to enhance its pharmacokinetic profile and to ensure adequate antiretroviral activity. The absolute bioavailability of darunavir without ritonavir is only 37%; however, when darunavir is adminstered concurrently with ritonavir, systemic exposure to darunavir increases 14-fold. Limited data suggest adequate absorption of crushed darunavir tablets, both when swallowed and when administered via various enteral tubes. This report describes a case in which crushed darunavir tablets were administered to a critically ill patient through an orogastric feeding tube.