HIV InfectionsPhase 1NCT00032669
Therapeutic Drug Monitoring and Viral Resistance Testing in the Treatment of HIV-Infected Children
A Phase 1 study testing HAART in people with HIV Infections, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
This study will evaluate a new treatment strategy called therapeutic drug monitoring (TDM) in HIV-infected children and adolescents. TDM involves analyzing the virus, giving drugs the virus is most sensitive to, monitoring drug blood levels to make sure there is enough drug to work against the virus, and changing the… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- HIV Infections
- What is being tested?
- HAART
- How many people
- 34 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2002to Apr 2006
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- HIV-infected children between the ages of 0 and 21 years
- An indication for treatment with a PI containing antiretroviral regimen as defined by the 2001 Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection (one of the following):
- Clinical symptoms associated with HIV Infection (i.e., clinical categories A, B, or C)
- Evidence of immune suppression indicated by CD4 T-lymphocyte count or percentage (i.e., immune category 2 or 3)
- Age less than 12 months - regardless of clinical, immunologic, or virologic status
- High or increasing HIV RNA copy number
Show all 25Show fewer
- Rapidly declining CD4 T-lymphocyte number or percentage to values approaching those indicative of moderate immune suppression (i.e., immune category 2)
- Children failing current treatment as defined by the 2001 Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection (http://www.hivatis.org/) (one of the following):
- Less than a 10-fold decrease from baseline viral load in patients on a HAART regimen (combination regimen that includes a PI and/or NNRTI) after 8-12 weeks of therapy.
- Less than a 5-fold decrease in viral load from baseline in patients on non-HAART regimen (e.g., dual NRTI combinations)
- Viral load not suppressed to undetectable levels after 4-6 months of antiretroviral therapy
- Repeated detection of HIV RNA in patients who initially responded to antiretroviral therapy with undetectable levels.
- An increase in viral load of greater than 3-fold.
- Change in immunologic classification
- For children in immunologic category 3, a decline of five percentiles or more in CD4 cell percentage
- A greater than 30 percentage decline in absolute CD4 cell count.
- Progressive neurodevelopmental deterioration
- Growth failure
- Disease progression
- Intolerant to or are showing evidence of toxicity from other antiretroviral treatments.
- HIV RNA greater than or equal to 5,000 copies per/ml within the past 3 months (may be from outside institution).
- Sexually active patients must be willing to use a medically acceptable form of birth control, which includes abstinence, while they are on this study.
- Hematologic Function: Total WBC greater than 1,500/mm(3), Absolute Neutrophil Count greater than 750/mm(3), hemoglobin greater than 8.0 gm/dL and platelet count greater than 75,000/mm(3) at study entry
- Hepatic Function: Liver transaminases must be less than or equal to 3.0 times the upper limit of normal; Lipase less than 1.5 times the upper limit normal; Creatine phosphokinase (CPK) less than 2.5 times the upper limit of normal.
- Renal Function: Patients must have an age-adjusted normal serum creatinine OR a creatinine clearance greater than or equal to 70mL/min/1.73.
Who cannot join
- History of non-adherence that in the opinion of the PI or study chairperson makes it unlikely that the patient will adhere to protocol.
- Clinically significant, unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction) which in the judgement of the Principal Investigator or Chairperson would compromise the patient's ability to tolerate this therapy or is likely to interfere with the study procedures or results
- Weight less than 10 kg.
- Pregnant or breast feeding females.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Cancer Institute (NCI)
Bethesda, Maryland, 20892
About this study
This study will evaluate a new treatment strategy called therapeutic drug monitoring (TDM) in HIV-infected children and adolescents. TDM involves analyzing the virus, giving drugs the virus is most sensitive to, monitoring drug blood levels to make sure there is enough drug to work against the virus, and changing the drug dose if it is too low.
HIV-infected children between 0 and 21 years of age who may benefit from treatment with a protease inhibitor and who are not benefiting from their current antiretroviral drug treatment regimen may be enrolled in this 48-week study. Patients who are not currently receiving antiretroviral treatment, including patients who have never received antiretroviral treatment, may be enrolled in the study.
Read more
Participants will have blood drawn to learn what anti-HIV drugs the patient's virus is resistant to-that is, what drugs are no longer effective against the virus. This is determined by analyzing the virus's genotype (detailed genetic structure) and phenotype (response to exposure to anti-viral drugs). Based on these test results and the patient's prior medication history, a drug regimen tailored to the individual patient will be prescribed. It may include one or two nucleoside reverse transcriptase inhibitors, such as zidovudine, didanosine, lamuvidine, zalcitabine, stavudine), a non- nucleoside reverse transcriptase inhibitor such as nevirapine or efavirenz, and a protease inhibitor such as amprenavir, nelfinavir, saquinavir, ritonavir, or Kaletra (a combination of lopinavir and ritonavir).
After the patients begin treatment, the amount of the protease inhibitor in the blood will be measured. If not enough of the drug is found in the blood, the dose of the drug will be increased and the amount of the drug in the blood will be checked again. In this study, the dose may be increased up to three times.
Patients will be seen in clinic for 6 days when treatment begins to measure blood levels of the medicines and evaluate the response of the virus. Treatment will then continue on an outpatient basis. Drug levels will be measured periodically throughout the study. The viral load will also be measured and additional tests to determine whether the resistance pattern of the patients' virus has changed. In addition, patients will undergo the following tests and procedures at various times throughout the study, more frequently for the first few months and then less often:
- Blood tests to measure cell counts and viral load
- Routine laboratory tests to measure kidney, liver, bone marrow, and other organ functioning
- Eye and neuropsychologic examinations
- Echocardiogram (heart ultrasound)
- Electrocardiogram (EKG - heart rhythm test)
- Chest X-ray
- Computed tomography (CT) scan of the head
- Skin tests
To make sure the medicines work, they must be taken as directed. In addition, since higher than usual doses of some of the anti-HIV drugs may be given, it will be important to know whether the patients are taking all of the medicine that has been prescribed. This study will therefore also measure patients' adherence to their medication regimen in two ways: 1) some medicines will be packaged in a bottle with an electronic medicine bottle cap that will record when the bottle is opened, and 2) patients and their parents will be interviewed by phone or in person at various times during the study about adherence and may be asked to fill out forms that record the number of doses taken. This will allow the doctor and patient to work together to make sure the medicines are being taken properly. Patients and parents will also be interviewed periodically about their understanding of HIV disease, about social supports that are available, and about the child's emotional adjustment.
Read the detailed description
This is a single arm study to determine whether a novel dose adjustment strategy that individualizes protease inhibitor dosing to maintain drug concentrations above virologic-based threshold values (TDM) in pediatric patients with HIV is able to result in a potentially clinically useful proportion of patients who achieve a targeted inhibitory quotient (IQ). The study will consist of up to 34 children between 0 and 21 years of age (minimum weight 10 kg). Patients will have viral resistance testing performed at baseline and that information, combined with treatment history analysis and drug tolerability issues will be used to design a combination antiretroviral regimen. After the new regimen is started, pharmacokinetic monitoring will guide dose adjustments of protease inhibitors. An algorithm will be followed to make dose adjustments based upon viral phenotype and drug levels. The primary outcome measure will be the fraction of patients who attain adequate protease inhibitor levels above target values. Secondary measures will include virologic and immunologic benefits and evaluation of toxicity and tolerability.
- Conditions
- HIV Infections
- Being tested
- HAART
- Keywords
- Antiretrovirals, Adherence, Dose Adjustments, Genotypic Resistance, Phenotypic Resistance
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HAARTDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Mar 2002 (estimated)
- Study startMar 2002
- Study completionApr 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Enrolment
- 34 participants
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00032669
- Sponsor's protocol ID
- 020150
- Other IDs
- 02-C-0150
- Status last verified
- Apr 2006
- First submitted
- 27 Mar 2002
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
Nachman SA, Stanley K, Yogev R, Pelton S, Wiznia A, Lee S, Mofenson L, Fiscus S, Rathore M, Jimenez E, Borkowsky W, Pitt J, Smith ME, Wells B, McIntosh K. Nucleoside analogs plus ritonavir in stable antiretroviral therapy-experienced HIV-infected children: a randomized controlled trial. Pediatric AIDS Clinical Trials Group 338 Study Team. JAMA. 2000 Jan 26;283(4):492-8. doi: 10.1001/jama.283.4.492.
PubMed 10659875Gulick RM, Mellors JW, Havlir D, Eron JJ, Gonzalez C, McMahon D, Richman DD, Valentine FT, Jonas L, Meibohm A, Emini EA, Chodakewitz JA. Treatment with indinavir, zidovudine, and lamivudine in adults with human immunodeficiency virus infection and prior antiretroviral therapy. N Engl J Med. 1997 Sep 11;337(11):734-9. doi: 10.1056/NEJM199709113371102.
PubMed 9287228Palella FJ Jr, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, Aschman DJ, Holmberg SD. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N Engl J Med. 1998 Mar 26;338(13):853-60. doi: 10.1056/NEJM199803263381301.
PubMed 9516219
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Therapeutic Drug Monitoring and Viral Resistance Testing in the Treatment of HIV-Infected Children
- ClinicalTrials.gov ID
- NCT00032669
- Acronym / sponsor ID
- 020150
- Conditions
- HIV Infections
- Keywords
- Antiretrovirals, Adherence, Dose Adjustments, Genotypic Resistance, Phenotypic Resistance
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Mar 2002
- Study completion
- Apr 2006
- First posted
- 28 Mar 2002 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will evaluate a new treatment strategy called therapeutic drug monitoring (TDM) in HIV-infected children and adolescents. TDM involves analyzing the virus, giving drugs the virus is most sensitive to, monitoring drug blood levels to make sure there is enough drug to work against the virus, and changing the drug dose if it is too low.
HIV-infected children between 0 and 21 years of age who may benefit from treatment with a protease inhibitor and who are not benefiting from their current antiretroviral drug treatment regimen may be enrolled in this 48-week study. Patients who are not currently receiving antiretroviral treatment, including patients who have never received antiretroviral treatment, may be enrolled in the study.
Participants will have blood drawn to learn what anti-HIV drugs the patient's virus is resistant to-that is, what drugs are no longer effective against the virus. This is determined by analyzing the virus's genotype (detailed genetic structure) and phenotype (response to exposure to anti-viral drugs). Based on these test results and the patient's prior medication history, a drug regimen tailored to the individual patient will be prescribed. It may include one or two nucleoside reverse transcriptase inhibitors, such as zidovudine, didanosine, lamuvidine, zalcitabine, stavudine), a non- nucleoside reverse transcriptase inhibitor such as nevirapine or efavirenz, and a protease inhibitor such as amprenavir, nelfinavir, saquinavir, ritonavir, or Kaletra (a combination of lopinavir and ritonavir).
After the patients begin treatment, the amount of the protease inhibitor in the blood will be measured. If not enough of the drug is found in the blood, the dose of the drug will be increased and the amount of the drug in the blood will be checked again. In this study, the dose may be increased up to three times.
Patients will be seen in clinic for 6 days when treatment begins to measure blood levels of the medicines and evaluate the response of the virus. Treatment will then continue on an outpatient basis. Drug levels will be measured periodically throughout the study. The viral load will also be measured and additional tests to determine whether the resistance pattern of the patients' virus has changed. In addition, patients will undergo the following tests and procedures at various times throughout the study, more frequently for the first few months and then less often:
- Blood tests to measure cell counts and viral load
- Routine laboratory tests to measure kidney, liver, bone marrow, and other organ functioning
- Eye and neuropsychologic examinations
- Echocardiogram (heart ultrasound)
- Electrocardiogram (EKG - heart rhythm test)
- Chest X-ray
- Computed tomography (CT) scan of the head
- Skin tests
To make sure the medicines work, they must be taken as directed. In addition, since higher than usual doses of some of the anti-HIV drugs may be given, it will be important to know whether the patients are taking all of the medicine that has been prescribed. This study will therefore also measure patients' adherence to their medication regimen in two ways: 1) some medicines will be packaged in a bottle with an electronic medicine bottle cap that will record when the bottle is opened, and 2) patients and their parents will be interviewed by phone or in person at various times during the study about adherence and may be asked to fill out forms that record the number of doses taken. This will allow the doctor and patient to work together to make sure the medicines are being taken properly. Patients and parents will also be interviewed periodically about their understanding of HIV disease, about social supports that are available, and about the child's emotional adjustment.
Detailed description
This is a single arm study to determine whether a novel dose adjustment strategy that individualizes protease inhibitor dosing to maintain drug concentrations above virologic-based threshold values (TDM) in pediatric patients with HIV is able to result in a potentially clinically useful proportion of patients who achieve a targeted inhibitory quotient (IQ). The study will consist of up to 34 children between 0 and 21 years of age (minimum weight 10 kg). Patients will have viral resistance testing performed at baseline and that information, combined with treatment history analysis and drug tolerability issues will be used to design a combination antiretroviral regimen. After the new regimen is started, pharmacokinetic monitoring will guide dose adjustments of protease inhibitors. An algorithm will be followed to make dose adjustments based upon viral phenotype and drug levels. The primary outcome measure will be the fraction of patients who attain adequate protease inhibitor levels above target values. Secondary measures will include virologic and immunologic benefits and evaluation of toxicity and tolerability.
Study design
- Primary purpose
- Treatment
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (25 listed)
- HIV-infected children between the ages of 0 and 21 years
- An indication for treatment with a PI containing antiretroviral regimen as defined by the 2001 Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection (one of the following):
- Clinical symptoms associated with HIV Infection (i.e., clinical categories A, B, or C)
- Evidence of immune suppression indicated by CD4 T-lymphocyte count or percentage (i.e., immune category 2 or 3)
- Age less than 12 months - regardless of clinical, immunologic, or virologic status
Key exclusion criteria (4 listed)
- History of non-adherence that in the opinion of the PI or study chairperson makes it unlikely that the patient will adhere to protocol.
- Clinically significant, unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction) which in the judgement of the Principal Investigator or Chairperson would compromise the patient's ability to tolerate this therapy or is likely to interfere with the study procedures or results
- Weight less than 10 kg.
- Pregnant or breast feeding females.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HAART | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2008.
- Background: PubMed 10659875Nachman SA, Stanley K, Yogev R, Pelton S, Wiznia A, Lee S, Mofenson L, Fiscus S, Rathore M, Jimenez E, Borkowsky W, Pitt J, Smith ME, Wells B, McIntosh K. Nucleoside analogs plus ritonavir in stable antiretroviral therapy-experienced HIV-infected children: a randomized controlled trial. Pediatric AIDS Clinical Trials Group 338 Study Team. JAMA. 2000 Jan 26;283(4):492-8. doi: 10.1001/jama.283.4.492.
- Background: PubMed 9287228Gulick RM, Mellors JW, Havlir D, Eron JJ, Gonzalez C, McMahon D, Richman DD, Valentine FT, Jonas L, Meibohm A, Emini EA, Chodakewitz JA. Treatment with indinavir, zidovudine, and lamivudine in adults with human immunodeficiency virus infection and prior antiretroviral therapy. N Engl J Med. 1997 Sep 11;337(11):734-9. doi: 10.1056/NEJM199709113371102.
- Background: PubMed 9516219Palella FJ Jr, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, Aschman DJ, Holmberg SD. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N Engl J Med. 1998 Mar 26;338(13):853-60. doi: 10.1056/NEJM199803263381301.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing HAART in people with HIV Infections, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 25 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Mar 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00032669, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2008.