Page 108 - HIV/AIDS Guidelines

Exposure-Response Relationship and Therapeutic Drug Monitoring (TDM) for Antiretroviral
Agents (Last updated January 10, 2011; last reviewed January 10, 2011)

Panel’s Recommendations

• Therapeutic drug monitoring (TDM) for antiretroviral (ARV) agents is not recommended for routine use in the
management of the HIV-infected adult (CIII).
• TDM may be considered in selected clinical scenarios, as discussed in the text below.

Rating of Recommendations: A = Strong; B = Moderate; C = Optional
Rating of Evidence: I = data from randomized controlled trials; II = data from well-designed nonrandomized trials or observational
cohort studies with long-term clinical outcomes; III = expert opinion
Knowledge of the relationship between systemic exposure (or concentration) and drug responses (beneficial
and/or adverse) is key in selecting the dose of a drug, in understanding the variability in the response of
patients to a drug, and in designing strategies to optimize response and tolerability.

TDM is a strategy applied to certain antiarrhythmics, anticonvulsants, antineoplastics, and antibiotics that
utilizes measured drug concentrations to design dosing regimens to improve the likelihood of the desired
therapeutic and safety outcomes. The key characteristic of a drug that is a candidate for TDM is knowledge
of the exposure-response relationship and a therapeutic range of concentrations. The therapeutic range is a
range of concentrations established through clinical investigations that are associated with a greater
likelihood of achieving the desired therapeutic response and/or reducing the frequency of drug-associated
adverse reactions.

Several ARV agents meet most of the characteristics of agents that can be considered candidates for a TDM
1
strategy. The rationale for TDM in managing antiretroviral therapy (ART) derives from the following:
• data showing that considerable interpatient variability in drug concentrations exists among patients who
take the same dose;

• data indicating that relationships exist between the concentration of drug in the body and anti-HIV effect
and, in some cases, toxicities; and

• data from small prospective studies demonstrating that TDM improved virologic response and/or
decreased the incidence of concentration-related drug toxicities. 2-3

TDM for ARV agents, however, is not recommended for routine use in the
management of the HIV-infected adult (CIII).

Multiple factors limit the routine use of TDM in HIV-infected adults. 4-5 These factors include:

• lack of large prospective studies demonstrating that TDM improves clinical and virologic outcomes.
(This is the most important limiting factor for the implementation of TDM at present.);

• lack of established therapeutic range of concentrations for all ARV drugs that is associated with
achieving the desired therapeutic response and/or reducing the frequency of drug-associated adverse
reactions;
• intrapatient variability in ARV drug concentrations;
• lack of widespread availability of clinical laboratories that perform quantitation of ARV concentrations
under rigorous quality assurance/quality control standards; and
• shortage of experts to assist with interpretation of ARV concentration data and application of such data to
revise patients’ dosing regimens.

Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents H-15

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