Efavirenz levels above recommended upper target in 20% of African patients in Senegal

Simon Collins, HIV i-Base

Gilles Peytavin and colleagues from Bichat-Claude Hospital, Paris, presented data on efavirenz plasma concentrations from two pilot studies involving 80 African patients from Senegal. [1]

Previous research has shown higher plasma levels of efavirenz in African patients and linked clearance rates to single nucleoside polymorphisms in CYP2B6, 3A4, 3A5 and MDR1 enzymes. [2, 3, 4] With these mutations being more common in African compared to Caucasian populations, and efavirenz being a key component of first-line regimens in ARV roll-out programmes, PK data in these populations is important,

Patients initiated regimens using efavirenz/3TC plus either ddI/EC or d4T; and efavirenz plasma levels were measured at month 1 and 6 using HPLC and referenced to the standard range of 1,000-4,000 ng/mL. This was a largely male study (86%), with baseline characteristics including median age 35, CD4 count 143 cells/mm3 (93-213) and viral load 5.6 log copies/mL (5.2-5.8).

Patients responded immunologically and virologically to treatment (~ CD4 increase +113 cells/mm3; 67% < 50 copies/mL), and treatment was reported as well tolerated.

However, plasma concentrations were found to be below minimum target in 12% and 4% of patients, and above the maximum target in 21% and 23%, at months 1 and 6 respectively. Inter-patient variability was approximately 100% and there was a statistically significant relationship between patients levels at each time point (p<0.0001).

Although the study reported no difference in efavirenz levels by gender, and that despite the higher levels treatment was ‘well tolerated’, further detail on the relationship between efficacy, tolerability and drug levels was not provided.


Unusually for an African cohort, there was a majority of male participants in this study (86% male]. Earlier studies (Taylor et al) have suggested that higher efavirenz levels are more likely in African women than men, but this group did not report a gender difference.

One remark from the floor following the presentation, was that these data were hard to interpret, given that patients weight were not recorded, making it impossible to evaluate any effect of weight change on drug levels.

Additional studies are required to understand whether the reduced efavirenz clearance in some patients may affect current recommendations for dose adjustment when using rifampicin-based TB medication.


  1. Peytavin G, Sow P, Ngom Gueye N et al. Efavirenz plasma concentrations in African Sub-Saharan HIV-infected patients. 7th International Workshop on Clinical Pharmacology of HIV Therapy, 20-22 April 2006, Lisbon. Abstract 1.
  2. Taylor S, Allen S, Fidler S et al. Stop study: after discontinuation of efavirenz, plasma concentrations may persist for two weeks or longer. 11th CROI 2004, Abstract 131.
  3. Ribaudo H, Clifford D, Gulick R et al. Relationships between efavirenz pharmacokinetics, side effects, drug discontinuation, virologic response, and race: results from ACTG A5095/A5097s. 11th CROI 2004, Abstract 132.
  4. Haas D, Ribaudo H, Kim R et al. A common CYP2B6 variant is associated with efavirenz pharmacokinetics and central nervous system side effects: AACTG Study NWCS214. 11th CROI 2004, Abstract 133.

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