- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00006494
Study of Tests to Evaluate Effectiveness of Anti-HIV Drugs
An Assessment of the Relationship Between Antiretroviral Drug Genotype/Phenotype (IC50) and Antiretroviral Activity in HIV-Infected, Drug-Experienced Patients With Suboptimal Suppression of Plasma Viral Load
The purpose of this study is to determine how laboratory tests called genotyping and phenotyping assess the effectiveness of antiretroviral drugs used to treat HIV infection. Some HIV-infected patients have measurable levels of virus in their blood even though they are taking combination drug therapy-including didanosine, stavudine, or efavirenz-against HIV. Genotyping and phenotyping can be used to test for resistance to a specific drug, thereby providing information that can help doctors decide on optimal drug treatment for a given patient. Genotyping identifies mutations, or changes, the virus undergoes that allow it to continue to grow despite drug treatment. Phenotyping involves growing the virus in test tubes with different amounts of drug and then calculating how much drug is required to stop its growth.
Patients 18 years of age and older with HIV infection and viral levels between 5000 and 100,000 copies per milliliter of blood who have been taking antiretroviral therapy for at least 6 months may be eligible for this study. Candidates will be screened with a urine test and various blood tests, including genotyping and phenotyping.
Participants will have a series of tests to determine whether or not a drug is active against HIV. This involves temporarily stopping the drug under study (i.e., either efavirenz or didanosine or stavudine). The study procedure is as follows:
- Patients will have six blood tests over 10 days to measure viral load while on all current anti-HIV medications. On one of those days two blood tests will be done to measure levels of didanosine or stavudine. Efavirenz will also be measured if this drug is to be stopped.
- The patient will temporarily stop the drug under while continuing to take the other drugs. (Efavirenz will be stopped for 3 weeks; stavudine and didanosine will be stopped for 2 weeks.) Seven blood tests will be done at the following intervals to measure viral load: For patients who stop efavirenz, blood will be drawn on days 13, 18, 20, 22, 24,28 and 30. (Day 0 is the first day of the study.) Patients who stop stavudine or didanosine will have blood drawn on days 11, 13, 15, 17, 19, 22 and 24. Repeat genotype and phenotype testing will also be done during this time, and a CD4 count (measurement of a certain type of white blood cell) will be done at the end of this 2- or 3-week period.
- The drug that was stopped will be restarted and viral load tests will be repeated. For pati...
Study Overview
Status
Conditions
Detailed Description
Study Type
Enrollment (Actual)
Contacts and Locations
Study Locations
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Maryland
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Bethesda, Maryland, United States, 20892
- National Institutes of Health Clinical Center, 9000 Rockville Pike
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Bethesda, Maryland, United States, 20889
- National Naval Medical Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
- INCLUSION CRITERIA:
In order to enroll, subjects must:
Be HIV infected.
Be currently receiving highly active anti-retroviral therapy. Drugs available through expanded access or compassionate use protocols are permitted.
Have received at least 6 months of HAART therapy.
Currently be receiving and be willing to temporarily discontinue the selected antiretroviral for the indicated duration.
Have a viral load between 1,000 and 100,000 copies/ml within 6 weeks prior to screen or at screening.
If one value is greater than 100,000 copies and one value less, the average of the two viral loads will be used to determine eligibility. Similarly, if one value is less than 1,000 and one value greater than 1,000, the average viral load will be used to determine eligibility.
Have two viral load tests by bDNA method in the NIH laboratory that differ by less than 20% (log10bDNA) in the three weeks prior to enrollment. Viral loads performed through participation in another NIAID study are acceptable. Alternatively, new patients coming to the clinic are permitted to have two screening visits.
Have a CD4 T cell number greater than 100 cells within 4 weeks of enrollment or greater than 100 cells within 8 weeks of enrollment if no more recent CD4 cell count is available.
Be adults age 18 or older.
Self-report adequate adherence to antiviral medications (missing at most one dose of drug weekly) and commit to work towards adherence during study participation.
EXCLUSION CRITERIA:
In order to enroll, subjects must not:
Have a positive pregnancy test.
Have evidence of recent HIV infection, defined as a history of a negative HIV ELISA within 12 months of screening.
Have any acute infection that might alter viral load with the previous 4 weeks.
Have received a vaccine in the previous 4 weeks.
Have symptomatic HIV disease for which rapid institution of a salvage regimen would be advisable.
Be receiving concomitant medications or have a concomitant illness with malabsorption or emesis that could be expected to result in inadequate concentrations of antiretroviral drugs.
Be receiving an anti-retroviral regimen that includes drugs that should not be used concomitantly (e.g., stavudine and zidovudine) or inadvisable dosages of antiretroviral agents.
Have any laboratory abnormality for which withdrawal of a drug or drug regimen might be considered. For the purposes of general guidance, Grade III toxicities would result in exclusion from study with the exception of stable thrombocytopenia or proteinuria or elevated bilirubin resulting from Gilbert's syndrome or indinavir treatment. Grade II SGOT or SGPT might be a reason for study exclusion if not explained by underlying hepatitis or if in a pattern of recent increase over a stable baseline.
Have genotypic evidence at screening that would suggest that discontinuing the selected antiretroviral would result in suboptimal therapy that would clearly place the remainder of the regimen at risk for the development of new resistance mutations during the discontinuation period. Two prominent possibilities would be patients taking NNRTI regimens and discontinuing NRTIs or PI component in patients who have genotypes with no NNRTI mutations. During the discontinuation period, it would be possible that the patient may acquire new resistance mutations to NNRTIs. Genotype may be performed as part of the screen or be performed through PMD.
Have had a change in antiretroviral regimen in the past 6 weeks.
Have received cytotoxic chemotherapy including hydroxyurea in the last 6 weeks, or have anticipated need for chemotherapy during study.
Have evidence of active hepatitis B infection and wish to interrupt either tenofovir or 3TC.
Have any suggestion of a trend to increase or decrease in viral load in the past 6 weeks.
Have significant active substance abuse or psychiatric illness that might interfere with study assessments or with your ability to return for study visits.
Study Plan
How is the study designed?
Collaborators and Investigators
Publications and helpful links
General Publications
- Lucas GM, Chaisson RE, Moore RD. Highly active antiretroviral therapy in a large urban clinic: risk factors for virologic failure and adverse drug reactions. Ann Intern Med. 1999 Jul 20;131(2):81-7. doi: 10.7326/0003-4819-131-2-199907200-00002.
- Deeks SG, Hecht FM, Swanson M, Elbeik T, Loftus R, Cohen PT, Grant RM. HIV RNA and CD4 cell count response to protease inhibitor therapy in an urban AIDS clinic: response to both initial and salvage therapy. AIDS. 1999 Apr 16;13(6):F35-43. doi: 10.1097/00002030-199904160-00001.
- Hirsch MS, Brun-Vezinet F, D'Aquila RT, Hammer SM, Johnson VA, Kuritzkes DR, Loveday C, Mellors JW, Clotet B, Conway B, Demeter LM, Vella S, Jacobsen DM, Richman DD. Antiretroviral drug resistance testing in adult HIV-1 infection: recommendations of an International AIDS Society-USA Panel. JAMA. 2000 May 10;283(18):2417-26. doi: 10.1001/jama.283.18.2417.
Study record dates
Study Major Dates
Study Start
Study Completion
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 010004
- 01-I-0004
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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