With Rilpivirine for HIV, Consider Patient`s Access to Food

By Lorraine L. Janeczko

NEW YORK (Reuters Health) - When doctors prescribe rilpivirine for HIV-1, they should consider patients' access to food, new research from Uganda suggests.

"Patients with HIV should always take their daily dose of the single tablet containing TDF/FTC/RPV (tenofovir disoproxil fumarate, emtricitabine plus rilpivirine) with food. When Ugandan HIV patients took the tablet without food, blood levels of rilpivirine decreased," wrote lead author Dr. Mohammed Lamorde of Makerere University in Kampala, Uganda, in email to Reuters Health.

"However, the expected levels of rilpivirine were attained when the tablet was taken with either a low-fat or a moderate-fat local meal," he added.

Dr. Lamorde and colleagues analyzed the effect of food on the steady-state pharmacokinetics of rilpivirine in HIV-1-infected patients and reported their findings online February 3 in the Journal of Antimicrobial Chemotherapy.

The 15 participants, aged 18 through 65, had been receiving tenofovir disoproxil fumarate and efavirenz plus either emtricitabine or lamivudine for six months or longer.

For 56 days, the researchers switched them to one daily TDF/FTC/RPV tablet and held their previous antiretroviral drugs. Between days one and 41, patients self-administered TDF/FTC/RPV with their usual diet to allow efavirenz to be eliminated and minimize the risk of the drug's effect on cytochrome P 450 3A4.

On day 42, they took TDF/FTC/RPV after an overnight fast. On day 49, they took the drug with a low-fat breakfast (353 kcal), and on day 56, they took it with a moderate-fat breakfast (589 kcal).

At those visits, they also received food baskets containing items for preparing five study meals at home over the next five days. Researchers taught them how to prepare the meals and reminded them to take their medication at home with food. (The authors could not verify, however, that participants actually ate the study meals they prepared at home and did not share them with other people.)

"For safety reasons, our study could only simulate dosing with a single missed meal, and this had no clinical significance in our study subjects," Dr. Lamode said. "In real world settings, dosing with rilpivirine without food for several days could decrease rilpivirine levels in blood beyond levels seen in this study."

On day 56, the researchers assessed the viral load, and the next day, the patients returned to their original antiretroviral medication.

The pre-dose concentrations of rilpivirine did not change during the study. Except for concentration at 24 hours (C24), pharmacokinetics were similar when patients took TDF/FTC/RPV with a low-fat or a moderate-fat meal.

Rilpivirine C24 significantly increased, by 15%, when taken with a low-fat, compared with a moderate-fat, meal; and it decreased significantly, by 21%, in the fasted state compared with a moderate-fat meal.

Compared with taking TDF/FTC/RPV with a moderate-fat meal, a single missed meal at the time of dosing led to a 16% reduction in rilpivirine's area under the curve (AUC), which the authors wrote is "unlikely to be clinically significant, assuming patients adhere to rilpivirine and take subsequent doses with food."

Rilpivirine peak serum concentration (Cmax) was similar under all three meal conditions and virological suppression was unchanged at study end.

Dr. MarkAlain Dery, of Tulane University School of Medicine in New Orleans, Louisiana, who was not involved in the study, told Reuters Health by email, "This study confirmed that rilpivirine needs to be taken with food. In resource-poor countries with food instability, rilpivirine should be taken preferably at the same time every day with a daily meal."

"When living day to day where food and housing are a constant struggle, HIV care is low on the list of daily personal considerations. If, however, once-daily rilpivirine can be used to treat those with food and housing insecurities, I would accept the risks of an occasional meal being skipped. With extreme food instability, it would still be advisable to continue rilpivirine, or any other antiretroviral therapy, and risk the chance of a virological breakthrough secondary to poor pharmacokinetics from poor absorption," added Dr. Dery.

Janssen Pharmaceutica, Belgium, funded the study and has financial relationships with three of the paper's 10 authors. .

Source: https://bit.ly/1ER5lib

J Antimicrob Chemother 2015.

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