Individualization of first line antiretroviral treatment with the use of therapeutic drug monitoring (TDM) in a resource limited settings.

Background: Availability and cost prevent low-medium income countries to access widely to new antiretroviral medications. Many HIV patients in Latin America still receive Efavirenz – EFV- or a boosted PI as third component of first line antiretroviral regimens. Most patients receiving boosted atazanavir -ATV/r- experience hyperbilirubinemia (main reason for treatment switch) and up to 20% of patients receiving efavirenz discontinue due to adverse effects. Although there are still options to optimize HIV treatments and potentially reduce the risk of withdrawal. We show our experience with managing the dosing of EFV or ATV with TDM. Methods & Materials: Hospital Italiano de Buenos Aires is a tertiary-care, university-affiliated hospital. For the past 4 years (EFV) and 2 years (ATV) we have had TDM available for antiretrovirals. From our HIV cohort we selected a convenience sample of patients that underwent TDM. Monitoring is performed through standard HPLC method. Results: EFV. 92 patients (16 female, 44.5 y mean) underwent TDM. Seventeen (18,4%) of the whole cohort and 50% from all patients with CNS symptoms had EFV levels above upper recommended range (4000 ng/ml). 4/5 were homozygous for TT genotype at position 516 of the CYP2B6 gene. Thirty eight patients (41%) had TDM performed due to adverse effects, 11 had treatment switch and 12 had a dose reduction of EFV leading in 10 to obtain normal plasma levels and improvement of symptoms, while maintaining efficacy. Three additional patients had plasma levels below recommended range (1000 ng/ml) leading in 2 of them to improve adherence. ATV. 20 patients (4 female, 54.5 y mean) underwent TDM. Fifteen (75%) of the whole cohort and 8/8 (100%) from all patients tested due to hyperbilirubinemia had ATV plasma levels above upper recommended range (0,85 mcg/ml. From these patients, 4 underwent unboosting of ATV with 3 of them reaching normal plasma levels and significant improvement of clinical signs. Conclusion: Even in resource limited settings the use of TDM is feasible. Guided adjustment of EFV dose and withdrawal of ATV boosting allows for the improvement of toxicity while maintaining treatment efficacy in a significant number of patients avoiding unnecessary withdrawals through therapeutic individualization.