Response to

To the Editor The authors thank Dr. Guiard-Schmid and colleagues for their interest in our article.2 In our study, the drug levels were obtained before the next dose due time and we eliminated nonadherent patients by interview. Atazanavir (ATV) absorption is clearly altered by administration of acid-modifying agents; the degree to which this occurs is dependent on the potency of acid-suppressing agents.3-5 Current recommendations are to avoid the proton pump inhibitors (PPIs) and to separate histamine-2 blockers (H2Bs) by 12 hours from ATV dosing.5 One should be quite cautious in interpreting drug levels because of major patient intervariability. In fact, the data from Guiard-Schmid and colleagues attest to high interpatient variability, where the range was 203 to 1976 ng/mL for the ATV/ritonavir combined with PPI group and 65 to 1944 ng/mL for the non-PPI group, allowing some patients to have inadequate levels. We are surprised by these findings, because the PPI group has slightly better levels than non-PPI group. It would be helpful to know the lower levels of sensitivity and the coefficient of variation for their assays. Furthermore, the median levels obtained by Guiard-Schmid et al (551 ng/mL in the PPI group vs. 469 ng/mL in the non-PPI group) may be adequate for naive patients but would be inadequate in patients with antiretroviral experience. Recent studies have shown that higher ATV concentration trough (Ctrough) levels (ie, 774-850 ng/mL) were more likely to reduce viral load (VL) in experienced patients.6-8 We are starting to understand the relation between drug levels and antiviral activity of the agents better, but many questions are still unanswered. One interesting issue is the intracellular levels of these agents and their relation to other drugs, particularly ritonavir, and viral suppression. We have seen patients in our cohort with undetectable serum levels of ATV and <50 HIV RNA copies/mL. There are also other reports showing lack of failure in these types of patients.9 Our group is currently in the process of investigating the intracellular levels and their relation to viral suppression. Until this information is available, it would be wise to follow the current recommendation on avoiding PPIs and separating H2Bs with ATV. Homayoun Khanlou, MD* Stan Louie, PharmD† Charles Farthing, MD* *AIDS Healthcare Foundation Sherman Oaks, CA and †University of Southern California, Los Angeles, Los Angeles, CA