In vitro studies have shown raltegravir cellular permeativity was decreased in the presence of the divalent cations magnesium and calcium, but not in the presence of the monovalent cation potassium. Raltegravir may bind to the divalent metals and form a metal-drug complex which is unable to cross the cell membrane.
Divalent metals and pH alter raltegravir disposition in Vitro. Moss DM, Siccardi M, Murphy M, at al. Antimicrob Agents Chemother, 2012, 56(6): 3020-6.

A case report describes a 39-year-old, HIV-1-infected man who experienced virologic failure while receiving a raltegravir-containing antiretroviral regimen with concomitant calcium administration. For drug interaction reasons, the patient was switched from a PI-based regimen to raltegravir/tenofovir/emtricitabine and calcium carbonate (1 g-vitamin D3 400 IU 3 times/day) was added for prevention of osteoporosis. After 10 months of an undetectable viral load and clinical evidence of a high level of adherence on this regimen, the patient 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. Therapeutic drug monitoring at the time of virologic failure showed lower than expected raltegravir concentrations at 5 hour post dose, but tenofovir and emtricitabine concentrations were within the expected range. The authors suggest that calcium binding to the divalent metal ion-chelating motif of raltegravir may have led to subtherapeutic raltegravir levels in this patient.
Virologic failure with a raltegravir-containing antiretroviral regimen and concomitant calcium administration. Roberts JL, et al. Pharmacother, 2011, 31(10): 298e-302e.