Drug-drug interactions are a common obstacle among people living with HIV receiving antiretroviral therapy. This is especially true for those using PIs, widely known for their ability to compete with other medications for enzymes that regulate drug levels in the body. This can elevate blood levels of one or more drug, ultimately increasing the risk of side effects; it can also reduce blood levels of medications and reduce the effectiveness of treatment.

Among the important interactions to be added to all PI package inserts include those involving Revatio (slidenafil), Uroxatral (alfuzosin), Advair and Serevent (both contain salmeterol), Tracleer (bosentan), Adcirca (tadalafil) and colchicine.

Revatio, a version of the erectile dysfunction medication sildenafil, is prescribed to treat pulmonary arterial hypertension. It is contraindicated among people living with HIV using PIs, meaning that the drug should not be used under any circumstances.

Tracleer and Adcirca are also used to treat pulmonary arterial hypertension and should be used cautiously. According to the FDA, their doses may need to be adjusted when combined with protease inhibitors. The agency also warns against using Tracleer with the PI Reyataz (atazanavir) if a Norvir (ritonavir) booster is not also included.

Advair and Serevent are frequently prescribed to help manage symptoms of asthma, chronic obstructive pulmonary disease (COPD) and sometimes seasonal allergies. They should not be combined with protease inhibitors.

Uroxatral, used to treat benign prostatic hyperplasia (BPH) in men, is also contraindicated among people using HIV protease inhibitors.

Colchicine, a natural produce derived from the Colchicum genus of plant, is used to treat gout and familial Mediterranean fever. Depending on the PI used, dose adjustments may be necessary. Additionally, colchicine should be avoided among those who take PIs and have a history of either liver (hepatic) or kidney (renal) impairment.