Treatment of HIV-infected patients requires unavoidable polypharmacy, during which drug interactions can occur. Pharmacokinetic interactions are those that affect the absorption, distribution, metabolism, or excretion of a drug. Interactions that produce antagonistic, additive, or synergistic effects are considered pharmacodynamic interactions. Not all interactions are clinically adverse and in some cases, interactions can be beneficial. The objective of this chapter is to provide the clinician with a framework for understanding drug interactions by applying the principles of pharmacology in the context of HIV medicine.

Pharmacokinetic drug interactions

Absorption

The absorption of oral drugs is affected by several conditions such as fasting, gastric pH, and enteric P-glycoprotein (PGP) expression. Drug—food interactions are delineated in Table 19.1; also listed are antiretroviral drugs that may be administered without regard to food. Drugs that increase gastric pH include antacids (including the buffer in older formulations of didanosine), H2-receptor antagonists, and proton pump inhibitors. These drugs can impair the bioavailability of drugs that require a low pH for optimal absorption such as delavirdine, indinavir, itraconazole, and ketoconazole. This interaction can usually be avoided by administrating the gastric pH-raising agent 1–2 hours later [1–3]. Didanosine is an example of a drug much better absorbed in an alkaline environment because it is acid labile. The original formulation of didanosine included a buffer (calcium carbonate and magnesium hydroxide in tablets or citrate-phosphate in sachets) or had to be reconstituted in antacid.