Page 110 - HIV/AIDS Guidelines

(TPV) and MVC were derived only from studies in ART-experienced persons. It is likely that use of PIs
and NNRTIs in the setting of reduced viral susceptibility may require higher trough concentrations than
those needed for wild-type virus. The inhibitory quotient (IQ), which is the ratio of ARV drug
concentration to a measure of susceptibility (genotype or phenotype) of the patient’s strain of HIV to that
drug, may additionally improve prediction of virologic response—as has been shown, for example, with
DRV in ART-experienced persons. 10-11 Exposure-response data for DRV, ETR, and RAL are accumulating
but are not sufficient to recommend minimum trough concentrations. The median trough concentrations
for these agents in HIV-infected persons receiving the recommended dose are included in Table 9b.
Using Drug Concentrations to Guide Therapy. There are several challenges and considerations for
implementation of TDM in the clinical setting. Use of TDM to monitor ARV concentrations in a patient
requires multiple steps:

• quantification of the concentration of the drug, usually in plasma or serum;
• determination of the patient’s pharmacokinetic characteristics;
• integration of information on patient adherence;

• interpretation of the concentrations; and
• adjustment of the drug dose to achieve concentrations within the therapeutic range, if necessary.
Guidelines for the collection of blood samples and other practical suggestions can be found in a position
paper by the Adult AIDS Clinical Trials Group Pharmacology Committee. 4

A final caveat to the use of measured drug concentrations in patient management is a general one—drug
concentration information cannot be used alone; it must be integrated with other clinical information. In
addition, as knowledge of associations between ARV concentrations and virologic response continues to
accumulate, clinicians who employ a TDM strategy for patient management should consult the most current
literature.

Table 9a. Trough Concentrations of Antiretroviral Drugs for Patients Who Have Drug-Susceptible
Virus

Drug Concentration (ng/mL)

Suggested minimum target trough concentrations in patients with HIV-1 susceptible to the ARV drugs 2-9

Fosamprenavir (FPV) 400
(measured as amprenavir concentration)

Atazanavir (ATV) 150
Indinavir (IDV) 100
Lopinavir (LPV) 1000
a
Nelfinavir (NFV) 800
Saquinavir (SQV) 100–250

Efavirenz (EFV) 1000
Nevirapine (NVP) 3000

a Measurable active (M8) metabolite

Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents H-17

Downloaded from http://aidsinfo.nih.gov/guidelines on 12/8/2012 EST.