Using one anti-HIV (antiretrovirals, or ARV) medication to improve or "boost" the amount of drug that gets into your body (pharmacokinetics) is not a new concept. Various combinations of these have been developed and have shown to improve the number, percent and duration of response to these medications.
The primary drug used, quite successfully, in improving the pharmacokinetics of ARV is ritonavir (Norvir). Agents recently brought and on the way to market would never have made it out of Phase I/II trials were ritonavir not combined with them (lopinavir/ritonavir -- Kaletra and tipranavir/ritonavir -- Boehringer-Ingelheim's experimental protease inhibitor, respectively). Ritonavir in combination with other approved agents, such as indinavir (Crixivan), amprenavir (Agenerase), hard-gelatin saquinavir (Invirase) and soon atazanavir (Reyataz) has allowed clinicians to use these agents at altered doses and frequencies that would not be available otherwise. Perhaps the most important result of combining these agents with ritonavir is not that the results are that much better, but the ability of the patient to incorporate the dosing into their lives was significantly enhanced.
Taking ritonavir as part of ARV can have its drawbacks, however. Low-dose ritonavir can still impact triglycerides, and to a lesser degree cholesterol, but still carries serious drug interaction potential. This is, after all, why ritonavir is being used in the first place -- its ability to interfere with the body's breakdown of another medicine is such that a lower dose of the other agent (and usually less often dosed) can be used. This may help to improve the tolerability of the other agent, but close watch needs to be maintained on any and all other medicines (including non-ARV) a person may be taking. (Ask your pharmacist!)
Nelfinavir (Viracept) does not have much in the way of dosing changes when given with ritonavir. The way it is broken down and eliminated by the body is not impacted to any appreciable degree by ritonavir. It has been shown that a significant change can be seen in the amount of nelfinavir in the body from one dosing time to the next, but it was not due to a missed dose of another medication. Instead, the amount of nelfinavir that gets into the body has been shown to be affected by the amount and type of food ingested with it.
The original nelfinavir studies revealed that if a single 250 mg tablet was taken with food versus an empty stomach, the amount of drug in the blood (over the dosing interval -- or AUC, for "area under the curve") was one to two times as much. This is very important because a certain amount of drug has to be maintained in the body in order for a drug to work against the virus.
A recently reported study done in Europe (ATHENA) took patients on nelfinavir and sampled the amount of drug in their blood. They then took the patients with lower levels than what was considered acceptable and gave them more detailed instructions on eating around the time of their nelfinavir dose. Over 1/3 of the patients who then ate more (increased calories and fat) around the time of their nelfinavir dose had their levels come up into the acceptable range without having to alter their dose -- or take another medicine. This also increased the percent of persons with undetectable viral loads from 58.8% to 80.5% after one year.
This data was looked at in a more structured fashion by the manufacturer. Diets of 1,000 kcal (50% fat), 500 kcal (20% fat) and 125 kcal (20% fat) were compared to each other and then to fasting in the same subjects. It was presented that the amount of drug in the body when eating instead of fasting was 3-5 times as much compared to fasting. What was even more intriguing was that the amount of drug in the blood just before the next dose was more consistent and higher when the subjects ate instead of fasting.
On the heels of this information is the newest dosage unit of nelfinavir, the 625-mg tablet. Recently approved by the FDA, this new tablet allows patients to take two pills twice a day instead of the 10 daily needed with the 250-mg tablet strength. The tablets are fairly close in makeup with some minor differences seen in the amount of blue dye and silicon (more and less in the 625-mg tablet, respectively). However, just like with the 250-mg tablet, eating makes a difference in how much gets into the body. The amount of drug that got into the body was twice as much when taken with food compared to fasting.
As we continue to move further away from the "hit hard, hit early" and closer to the "wait and see" approach to treating HIV infection, what has remained consistent is the need to make every regimen count for as long as possible. Providing information on the importance of diet to each ARV should be a standard part of every counseling session with patients at every visit.
Patrick G. Clay, Pharm.D. is an Assistant Professor of Pharmacy Practice at the University of Missouri-Kansas City School of Pharmacy. He is also the HIV Clinical Specialist at the KC Free Health Clinic, 3515 Broadway, Kansas City, MO 64111. Dr. Clay can be reached by phone: (816) 777-2721; fax: (816) 753-0804; or e-mail: firstname.lastname@example.org. Editor's note: Please see "Viracept and Food" in News Briefs.)