Virologic Failure with a Raltegravir‐Containing Antiretroviral Regimen and Concomitant Calcium Administration

Raltegravir, an inhibitor of the human immunodeficiency virus‐1 (HIV‐1) integrase enzyme, is a preferred component of antiretroviral regimens for both treatment‐naïve and ‐experienced patients. Compared with other antiretroviral agents, raltegravir has less toxicity and fewer drug interactions since it is not a substrate, inhibitor, or inducer of cytochrome P450 enzymes. However, raltegravir is not devoid of drug interactions. We describe a 39‐year‐old, HIV‐1‐infected man who experienced virologic failure while receiving a raltegravir‐containing antiretroviral regimen with concomitant calcium administration. The patient was prescribed protease inhibitor‐based combination antiretroviral therapy, and within 2 months, he achieved undetectable plasma HIV‐1 RNA levels. Seven months after starting therapy, he developed a focal cerebral vasculitis of unknown etiology, which was treated with prednisone, aspirin, and acyclovir. Due to the potential for drug interactions between prednisone and protease inhibitors, the patient was switched to an antiretroviral regimen containing raltegravir. In addition, calcium carbonate 1 g‐vitamin D3 400 IU 3 times/day was started for prevention of osteoporosis associated with long‐term glucocorticoid use. After 10 months of an undetectable plasma HIV‐1 RNA level and clinical evidence of a high level of adherence, he subsequently developed detectable HIV‐1 RNA levels with documented resistance to raltegravir. His antiretroviral therapy was changed back to a protease inhibitor‐based regimen, and his HIV‐1 RNA level rapidly resuppressed. Calcium binding to the divalent metal ion‐chelating motif of raltegravir may have led to subtherapeutic raltegravir levels in this patient. It is important for clinicians to be aware of the potential interaction between polyvalent cation‐containing agents, such as calcium, and raltegravir.