What are the main reasons for one drug to be taken with food and other to be taken on an empty stomach? Is that for better absorption or for side effects to be lessened? Or there are other important issues?

There are several reasons why many HIV medications have food restrictions and must be taken either with food or on an empty stomach. The main reason is for better drug absorption. For example, some drugs are better absorbed if they are taken on an empty stomach, such as indinavir (Crixivan) and didanosine (Videx), while others clearly are better absorbed with/or after a meal, such as lopinavir/ritonavir (Kaletra) and darunavir (Prezista).

The presence or absence of food in your stomach can also alter the rate of absorption and may cause or prevent some unwanted side effects. For example, taking food with nelfinavir (Viracept) may decrease the severity of loose stool; while taking fatty food with the efavirenz (Sustiva, Stocrin) may cause more dizziness and sleep disturbance.

Another important factor that may affect the absorption of some HIV medications is the acidity in your stomach. Gastric acid, or stomach pH levels decrease when eating, thus medications that require low pH (more acid) are best taken with food. There are medications, such as ant-acids, H2 Blockers and PPI (Proton-Pump_Inhibitors) that can affect the acidity level in your stomach, affecting then the absorption of some medications. The typical example here is atazanavir (Reyataz). Luckily most HIV medications can be taken without regardless of food, but you should always check with the medication information that is provided by your pharmacist to learn the correct way to take your medications. For the most part, if you are required to take your medications with meal, at the very least, try to eat something with it, even if it is something light.