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One Third on First-Line Antiretrovirals
Have Clinically Significant Drug Interactions
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50th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), September 12-15, 2010, Boston
Mark Mascolini
A chart review of antiretroviral-treated adults at the Albany Medical Center HIV clinic found that one third had clinically significant interactions involving antiretrovirals [1]. Compared with a raltegravir-based regimen, a nonnucleoside (NNRTI) regimen more than doubled the risk of drug interactions, while a protease inhibitor (PI) regimen raised the risk 5 times.
This study involved 229 people taking their first antiretroviral combination, including 108 (47.2%) taking a PI-based regimen, 81 (35.4%) taking an NNRTI-based regimen, and 40 (17.5%) taking a raltegravir regimen. The researchers collected demographics, clinical history data, and full medication profiles (including antiretrovirals) from each person's chart. They used Lexi-Comp DDI software to determine drug-drug interactions, and they defined clinically significant interactions as those considered contraindicated or not recommended without close monitoring, or those requiring a dose adjustment to avoid side effects.
The 229 patients had a median age of 47 years (range 24 to 78) and had been infected with HIV for a median of 14 years (range 1 to 25), with no significant differences between antiretroviral groups for either measure. Study participants were taking a median of 6 non-HIV drugs (range 0 to 30) and had a median of 3 comorbidities (range 0 to 18).
Two hundred people (87.3%) had one or more drug-drug interactions; the median number was 4 (range 1 to 63). There were 163 people (71.2%) with an interaction involving an antiretroviral and 78 (34.1%) with a clinically significant antiretroviral interaction.
The most frequent interactions involving antiretrovirals were atazanavir plus tenofovir in 22 people, a PI and a statin in 15 people, an NNRTI and a statin in 13 people, and a PI and a phosphodiesterase inhibitor (blood vessel relaxant) in 8 people. Six people each had the following three interactions: (1) NNRTI and a calcium channel blocker, (2) atazanavir and acid suppressant, (3) tenofovir and didanosine.
Four people were taking "strongly precautioned" drug combinations-3 taking a PI plus fluticasone (Flonase nasal spray, a glucocorticoid) and 1 taking nelfinavir and a proton pump inhibitor.
Only 2 people taking raltegravir (5%) had a clinically significant interaction involving an antiretroviral, compared with 20 (25%) taking an NNRTI and 56 (52%) taking a PI.
Multivariate analysis identified three variables that independently raised the risk of a clinically significant drug-drug interaction involving an antiretroviral:
--Taking more than 5 non-HIV drugs: RR 1.86, P < 0.001
--Taking an NNRTI (vs raltegravir): RR 2.48 (P < 0.001)
--Taking a PI (vs raltegravir): RR 4.96 (P < 0.001)
"When selecting antiretroviral regimens for an individual patient," the Albany investigators cautioned, "drug interaction potential should be considered an important differentiating feature."
Reference
1. Miller CD, Abdelsayed S, Veve M, Patel N. Predictors of clinically significant antiretroviral (ARV) drug interactions among first-line ARV regimens. 50th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). September 12-15, 2010. Boston. Abstract H-210.
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