Relationship between nevirapine concentrations and virological failure in a clinical setting

Previous studies have reported high frequency of sub-optimal nevirapine Ctrough levels but no guidelines have suggested a way to manage these patients. Should a clinician confirm the inadequate concentration on another sample because of high intra-patient variability or increase nevirapine dose?

N Machefert from the Centre Hospitalier Universitaire, Toxicologie et Pharmacocinétique, Poitiers, France and coworkers performed a retrospective assessment of the risk of virological failure in a clinical setting for patients having one or more sub-optimal nevirapine Ctrough (<3 ug/mL). Additionally, the study was to determine the extent of the intra-patient variability among this group.

The authors evaluated 38 patients receiving standard nevirapine dose as part of their antiretroviral regimen. Nevirapine Ctrough concentrations were determined from 245 samples collected at each clinic visit through out the course of their treatment. Viral load and adherence, recorded at each clinic visit, were also evaluated. Virological failure was defined as >1000 copies/mL. The number of patients with one or more Ctrough <3 ug/mL were compared to the virological failure group.

Patients received nevirapine for a mean of 700 days; 8/38 patients had virological failure. There were an average of 6 Ctrough measurements available per patient. The investigators found 24/ 38 (63%) patients had at least one inadequate Ctrough during the course of their treatment. 7/8 (88%) patients had more than one inadequate Ctrough in the viral failure group vs 9/30 patients in the group without virological failure, p=0.01. Additionally 6/8 patients in the virological group were considered as non-adherent (confirmed by undetectable plasma concentration measurement during the course of their treatment).

They reported that the intra-individual variability was significant with a mean value of 35% [range: 5-200%] in all patients but only 20% [range: 5-45%] excluding non-adherent patients. The investigators wrote: This study confirm the high frequency of inadequate Ctrough in clinical setting and suggest that only patients exhibiting more than one inadequate NVP Ctrough are at risk of virological failure. In routine practice, before nevirapine dosage adjustment, inadequate Ctrough should be confirmed and adherence should be assessed.

Machefert N, Dupuis A, Le Moal G et al. Relationship between nevirapine concentration and virological failure assessed in a clinical setting. 7th International Workshop on Clinical Pharmacology of HIV Therapy, 20-22 April 2006, Lisbon. Abstract 70.