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  11th International Workshop on Clinical Pharmacology of HIV Therapy
Sorrento, Italy
April 7-9, 2010
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Efavirenz Troughs Higher in People Over 50 Years Old
  11th International Workshop on Clinical Pharmacology and HIV Therapy, April 7-9, 2010, Sorrento
Mark Mascolini
Trough concentrations of efavirenz--but not of atazanavir, raltegravir, or darunavir--proved higher in people over 49 than in younger patients, according to results of a 134-person study in Rome [1]. Although earlier research linked higher efavirenz levels to toxicity [2], this new study did not determine whether older people had more efavirenz-related side effects than younger people.
Researchers from the INMI Lazzaro Spallanzani Infectious Diseases Department analyzed trough concentrations of efavirenz in 19 people, atazanavir in 28 people (18 using a ritonavir boost), darunavir in 40 people, and raltegravir in 47 people. Everyone in the analysis had therapeutic drug monitoring to assess either suspected drug-drug interactions (7%), toxicity (11%), adherence (12%), or virologic or immunologic failure (70%)..
All study participants were Caucasian, and 65% were men. Median age stood at 46 years (range 20 to 76), median body mass index at 23 kg/m(2) (range 17 to 38), and median CD4 count at 334 (range 9 to 1416). The investigators divided patients in those 39 or younger, those 40 to 49, and those 50 or older. CD4 counts and body mass index were similar from group to group for all four drugs assessed.
The average atazanavir trough was lower in the 9 troughs measured in people over 49 (1013 ng/mL +/- 808 standard deviation SD) than in the 16 troughs in people aged 40-to-49 (1968 ng/mL +/- 1582) or the 10 troughs in people under 40 (1483 ng/mL +/- 1143), but these differences were not statistically significant.
Average troughs were similar from group to group for raltegravir (210 ng/mL +/- 232 in the 23 troughs measured in people under 40 years old, 263 ng/mL +/- 307 in the 57 troughs in people in their 40s, and 177 ng/mL +/- 243 in the 28 troughs in people over 49) and for darunavir (2633 ng/mL +/- 1819 in the 19 troughs from people under 40, 3077 ng/mL +/- 2180 in the 46 troughs in people in their 40s, and 2581 ng/mL +/- 1402 in 17 troughs in people over 49).
Among the 19 people taking efavirenz, average troughs were higher in the 12 troughs in people over 49 years old (2949 ng/mL +/- 1464) than in the 7 troughs in people in their 40s (2147 ng/mL +/- 186, P = 0.08) and the 5 troughs in people under 40 (2097 ng/mL +/- 1069, P = 0.04)..
The researchers could make no linear correlations between age and trough concentration for any of the four antiretrovirals.
They suggested "special caution" may be needed to avoid additive neurologic toxicity in older people taking efavirenz and other medications that may have central nervous system side effects. The findings may raise a cautionary flag, but they require confirmation because of the small number of people taking efavirenz in this study and the lack of correlation with clinical side effects.
1. Tommasi C, Nicastri E, Gallo AL, et al. Pharmacological evaluation of new antiretroviral drugs in the elderly HIV-1 infected people. 11th International Workshop on Clinical Pharmacology and HIV Therapy. April 7-9, 2010. Sorrento. Abstract 56.
2. Marzolini C, Telenti A, Decosterd LA, Greub G, Biollaz J, Buclin T. Efavirenz plasma levels can predict treatment failure and central nervous system side effects in HIV-1-infected patients. AIDS. 2001;15:71-75.