Using Drug Levels in the Blood to Guide Therapy in HIV Infected Patients Taking a Protease Inhibitor

A Phase II Randomized Controlled Trial Evaluating the Impact of Therapeutic Drug Monitoring (TDM) on Virologic Response to a Salvage Regimen in Subjects With a Normalized Inhibitory Quotient (NIQ) Less Than or Equal to 1 to One or More Protease Inhibitors


Hauptsponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Quelle National Institute of Allergy and Infectious Diseases (NIAID)
Kurze Zusammenfassung

Drug resistance testing can be used to see which anti-HIV drugs are likely to suppress the growth of HIV and to select an anti-HIV regimen for HIV infected patients who have failed previous drug regimens. Therapeutic drug monitoring (TDM) is a process that involves measuring blood levels of a drug and may further increase the benefits that resistance testing offers by optimizing protease inhibitor (PI) drug concentrations. The purpose of this study is to determine whether changing the dose of PIs, as indicated by TDM, reduces the viral load in PI-experienced patients.

Hypothesis: Treatment-naive study participants who undergo TDM and whose clinicians' interpret their TDM results and adjust their PI doses will have better virologic response rates and decreased toxicities (and thus better treatment outcomes) than participants who do not undergo TDM.

detaillierte Beschreibung

The use of drug resistance testing to guide the selection of an antiretroviral regimen for patients in whom current therapy is failing has gained growing acceptance in clinical practice. Genotypic and phenotypic resistance testing has been associated with improved short-term virologic outcome in prospective interventional trials. There is also growing evidence that monitoring drug levels, particularly of PIs, may add to the benefit provided by resistance testing. This study will assess the impact of TDM and resistance testing on lowering viral load in treatment-experienced patients and will also evaluate the mean change in plasma HIV RNA from study entry to Step 2 of the study.

No antiretrovirals will be provided by this study. Participants will be followed for a maximum of 48 weeks. Participants failing at least one combination antiretroviral regimen will have a screening drug resistance test performed while remaining on the failing regimen. In Step 1, participants will begin a salvage antiretroviral regimen within 7 days of study entry selected by their clinician using results of the resistance test. Two weeks after initiation of the salvage regimen, participants will have timed plasma samples obtained for PI trough levels. The results of the trough level tests will be used to calculate a normalized inhibitory quotient (NIQ) in order to determine eligibility for randomization into Step 2 at Week 4. Electrocardiograms (EKGs) and trough levels will be performed at Weeks 2, 6, and 10; support interviews to promote adherence will also be conducted by the study nurse or clinician at these times. Some participants taking tipranavir may have additional blood collection at Week 2.

In Step 2, participants with an NIQ of 1 or less will be randomly assigned to one of two arms. Arm A participants will receive standard care (SC) only, while participants in Arm B will receive SC plus dose-adjusted PIs based on the NIQ. Clinical and viral load assessment will be conducted at screening, entry, and Weeks 4, 10, 16, 24, 32, 40, and 48. Arm B participants will also have their PI trough levels checked at Weeks 6 and 10. Participants with an NIQ greater than 1 will be assigned to observational Arm C (open to up to 50 enrollees) or will stop their involvement in the study. Participants in Arms A, B, or C who have a viral load of 1000 copies/ml or higher or who experience virologic failure at or after Week 24 will be eligible to receive a second resistance test and enter Step 3.

Participants in Step 3 will begin a second salvage regimen; PI trough levels will be measured after 2, 6, and 10 weeks of salvage therapy. Those with an NIQ greater than 1, or with an NIQ of 1 or less and do not wish to escalate dose, will be followed on Step 3 for a maximum of 48 weeks after study entry.

All participants are encouraged to coenroll in ACTG A5128, Consent for Use of Stored Patient Specimens for Future Testing.

Gesamtstatus Completed
Anfangsdatum June 2002
Fertigstellungstermin August 2007
Primäres Abschlussdatum April 2007
Phase Phase 3
Studientyp Interventional
Primärer Ausgang
Messen Zeitfenster
Change in log10 plasma HIV-1 RNA concentration from Step 2 entry (Week 4) to Week 24 (20 weeks post-randomization)
change in log10 plasma HIV-1 RNA concentration from study entry to Week 24 (20 weeks post-randomization)
Einschreibung 360

Interventionsart: Procedure

Interventionsname: Therapeutic Drug Monitoring (TDM)



Note: Enrollment into Arm C closed on 07/28/04 after reaching target accrual. Participants with a Week 2 NIQ of greater than 1 will be permanently discontinued from the study.

Inclusion Criteria for Step 1:

- HIV infected

- Viral load of 1000 copies/ml or more at study screening

- At least one viral load of 400 copies/ml or more within 6 months of study entry while on the failing antiretroviral regimen

- Virologic failure of at least one combination (two or more drugs) antiretroviral regimen, with at least one of these failing regimens containing a PI. Low dose ritonavir and hydroxyurea are not counted as antiretrovirals.

- Currently on a failing combination antiretroviral regimen

- Plan to initiate a salvage regimen containing a PI within 7 days of study entry

- Acceptable methods of contraception while receiving the study medications and for 6 weeks after stopping the medications. Participants who are currently taking efavirenz and who have undergone surgery to prevent conception (e.g., hysterectomy, tubal ligation, vasectomy) must provide physician's documentation of their current regimen and of their previous surgery.

- Resistance to at least one drug in the failing regimen, documented within 90 days of study entry

- Karnofsky performance scale of 70 or more within 30 days prior to study entry

Exclusion Criteria:

- Growth factors, interleukins, interferons (except for the treatment of hepatitis C), non-FDA approved systemic drugs, and HIV vaccines within 30 days of study entry

- Require certain medications prior to or during the study

- Certain heart conditions, if starting a PI-based regimen as the salvage regimen

- Acute illness or infection requiring treatment within 14 days of study entry

- Any condition that would limit ability to participate in the study

- Cancer requiring radiation or systemic chemotherapy

- Active drug or alcohol use or dependence that would interfere with the ability to meet study requirements

- Acute or chronic pancreatitis

- Planned use of hydroxyurea in the salvage regimen

- Pregnant or breastfeeding

Geschlecht: All

Mindestalter: 18 Years

Maximales Alter: N/A

Gesunde Freiwillige: No

Insgesamt offiziell
Univ of Alabama at Birmingham | Birmingham, Alabama, 35924-2050, United States
Univ of Southern California | Los Angeles, California, 90033-1079, United States
UCLA School of Medicine | Los Angeles, California, 90095, United States
Univ of California, San Diego Antiviral Research Center (AVRC) | San Diego, California, 92103, United States
Univ of California San Francisco | San Francisco, California, 94110, United States
San Mateo County AIDS Program | Stanford, California, 94305-5107, United States
Santa Clara Valley Med Ctr | Stanford, California, 94305-5107, United States
Willow Clinic | Stanford, California, 94305-5107, United States
Univ of Colorado Health Sciences Ctr | Denver, Colorado, 80262, United States
Univ of Miami | Miami, Florida, 33136-1013, United States
Univ of Hawaii | Honolulu, Hawaii, 96816-2396, United States
Northwestern Univ | Chicago, Illinois, 60611-3015, United States
The CORE Ctr | Chicago, Illinois, 60612, United States
Methodist Hosp of Indiana | Indianapolis, Indiana, 46202-1261, United States
Indiana Univ Hosp | Indianapolis, Indiana, 46202-5250, United States
Wishard Hosp | Indianapolis, Indiana, 46202, United States
Univ of Maryland, Institute of Human Virology | Baltimore, Maryland, 21201, United States
Johns Hopkins Univ | Baltimore, Maryland, 21287-8106, United States
Harvard (Masschusetts General Hosp) | Boston, Massachusetts, 02114, United States
Beth Israel Deaconess-West Campus | Boston, Massachusetts, 02215, United States
Brigham and Women's Hosp | Boston, Massachusetts, 02215, United States
Univ of Minnesota | Minneapolis, Minnesota, 55455-0392, United States
St. Louis Connect Care | St. Louis, Missouri, 63108-2138, United States
Washington Univ (St. Louis) | St. Louis, Missouri, 63108-2138, United States
SUNY-Buffalo (Rochester) | Buffalo, New York, 14215, United States
Beth Israel Medical Center | New York, New York, 10003, United States
Chelsea Clinic | New York, New York, 10011, United States
New York University - Bellevue | New York, New York, 10016, United States
Long Beach Memorial (Pediatric) | New York, New York, 10021, United States
Columbia Univ | New York, New York, 10032, United States
Community Health Network Inc | Rochester, New York, 14642, United States
Univ of Rochester Medical Center | Rochester, New York, 14642, United States
University of North Carolina | Chapel Hill, North Carolina, 27514, United States
Duke Univ Med Ctr | Durham, North Carolina, 27710, United States
Ohio State Univ | Cincinnati, Ohio, 45267-0405, United States
Univ of Cincinnati | Cincinnati, Ohio, 45267-0405, United States
Case Western Reserve Univ | Cleveland, Ohio, 44106, United States
Cleveland Clinic | Cleveland, Ohio, 44109-1998, United States
MetroHealth Med Ctr | Cleveland, Ohio, 44109-1998, United States
Univ of Pittsburgh | Pittsburgh, Pennsylvania, 15213, United States
Rhode Island Hosp | Providence, Rhode Island, 02906, United States
Stanley Street Treatment and Resource | Providence, Rhode Island, 02906, United States
The Miriam Hosp | Providence, Rhode Island, 02906, United States
Comprehensive Care Clinic | Nashville, Tennessee, 37203, United States
Univ of Texas, Galveston | Galveston, Texas, 77555-0435, United States
Univ of Washington (Seattle) | Seattle, Washington, 98104, United States
University of Puerto Rico | San Juan, 00936-5067, Puerto Rico
Standort Länder

Puerto Rico

United States


December 2008

Hat den Zugriff erweitert No
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Studiendesign Info

Zuweisung: Randomized

Hauptzweck: Treatment

Maskierung: None (Open Label)