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Response from Dr. Sherer

Although there are some uncertainties about medication adherence, medication timing is NOT one of them. There is enough solid information about adherence timing to allow you a high level of confidence that you are doing everything possible to maximize the likelihood that you get all of the best benefit from your ART regimen if your follow your doctor's instructions and the recommended dose intervals for your medications.
Yes, you should take the medications at the same time, simply because that is most convenient and allows you to take your medications in a regular, structured pattern that is the same every day. Epzicom is a once daily medication, and Kaletra can be taken either once or twice daily. For patients taking this regimen as their first ever regimen, or as their first regimen including a protease inhibitor, I do recommend taking the Kaletra tablets once daily.
If you and your doctor have chosen to use the Kaletra twice daily, then it should be taken at intervals as close to 12 hours as possible. In addition, I recommend that you always take this regimen with food, which can help to reduce some of the mild GI side effects.
Because Kaletra is a boosted PI, this regimen is considered to be more 'forgiving' than some other regimens. This means that it may allow you to be a little more variable in the exact dose interval, e.g. 1-2 hours on either side of dosing every 24 hours (for once daily dosing). The two features of the boosted PIs that make them more forgiving are 1) the higher drug levels that are acheived with boosting, often 20x or more higher than the level needed to inhibit the virus, and 2) the higher genetic barrier to resistance with boosted PIs. Resistance to Kaletra (also know as lopinavir/ritonavir or LPV/r) requires 6-8 separate amino acid mutations that require several steps and many months to develop.
In contrast, medications like lamivudine (Epivir or 3TC) and efavirenz (Sustiva, Stocrin, or EFV) require only a single amino acid mutation for reduced susceptibility, and this process can happen in hours to days in the setting of prolonged viremia.
Your best way to handle some of the uncertainties about medication adherence and timing is to talk to your doctor and work out a strategy that best meets your particular needs, your schedule, your lifestyle, eating habits, etc. I urge you to talk to your doctor about your questions and these observations.
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