TDM for HIV/AIDS

In spite of remarkable success with highly active antiretroviral therapy (HAART) in treating HIV-infected patients, not all patients respond optimally. One possible reason may be related to suboptimal drug levels in the blood. To suppress viral replication, it is critical for a patient to maintain adequate drug concentrations in the bloodstream throughout the dosing interval. TDM can help guide dosing decisions and plays a critical role in the HIV health care continuum.

Highly Active Antiretroviral Therapy (HAART)

Highly active antiretroviral therapy (HAART) involves the use of a combination of 3 or more drugs, usually from at least two classes. Currently, five classes of antiretroviral drugs have been approved by the FDA for treating HIV-infection:

  • Protease Inhibitors (PIs)
  • Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
  • Nucleoside Reverse Transcriptase Inhibitors (NRTIs)
  • Fusion Inhibitors
  • Integrase Inhibitors
  • Entry Inhibitors

Measuring Drug Levels

Even though antiretroviral drugs can suppress HIV replication, they are unable to completely eliminate it. Developing a 'magic bullet' drug or vaccine without side effects remains an ideal objective; however, the immediate goal is to utilize existing antiretroviral drugs in a more effective way while minimizing toxic side-effects. By routinely measuring the plasma levels of antiretroviral drugs the clinician can individualize HAART for an HIV-infected patient.

TDM and Inhibitory Quotient

A new and exciting area of clinical research combines drug levels and viral resistance information (the inhibitory quotient). Although determined in a number of ways, the inhibitory quotient essentially is the ratio of drug exposure over virological susceptibility to the drug. The inhibitory quotient is a promising tool in TDM, especially for the management of treatment-experienced patients taking protease inhibitors.

Guidelines for Therapeutic Management of Antiretroviral Drugs

“There are multiple scenarios in which both data and expert opinion indicate that information on the concentration of an antiretroviral agent may be useful in patient management,” according to Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents, (DHHS November 3, 2008). These scenarios include:

  • clinically significant drug-drug or drug-food interactions that may result in reduced efficacy or increased dose-related toxicities
  • changes in pathophysiologic conditions that may impair gastrointestinal, hepatic, or renal function and thereby potentially alter drug absorption, metabolism, or elimination
  • patients such as pregnant women who may be at risk for virologic failure because of altered pharmacokinetics resulting in plasma concentrations lower than those achieved in the typical patient
  • in treatment-experienced persons who may have viral isolates with reduced susceptibility to antiretroviral agents;
  • use of alternative dosing regimens whose safety and efficacy have not been established in clinical trials
  • patients experiencing concentration-dependent toxicities
  • lack of expected virologic response in a treatment-naive person.

Selected references:

British HIV Association. Treatment of HIV-infected adults with antiretroviral therapy.
Available at http://www.bhiva.org

La Porte CJ, Back DJ, Blaschke T, et al. Updated guideline to perform therapeutic drug monitoring for antiretroviral agents. Reviews in Antiviral Therapy. 2006;3:314.

Panel on Antiretroviral Guidelines for Adult and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. www.aidsinfo.nih.gov

Virology Education BV. Optimizing TDM in HIV Clinical Care: A practical guide to performing therapeutic drug monitoring (TDM) for antiretroviral agents. Available at www.HIVpharmacology.com.