HIV InfectionNCT00006494
Study of Tests to Evaluate Effectiveness of Anti-HIV Drugs
An observational study of HIV Infection, run by National Institute of Allergy and Infectious Diseases (NIAID) at 2 sites in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV Infection
- How many people
- 14 participants
- Where
- 2 sitesUnited States
- Study dates
- 7 Nov 2000to 6 Sep 2011
- Phase
- Observational
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
National Naval Medical Center
Bethesda, Maryland, 20889
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: 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.
Read more
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...
Read the detailed description
The efficacy of highly active antiretroviral therapy (HAART) is limited by the emergence of drug-resistant virus strains. Development of resistance to one or more antiretroviral drugs in a HAART regimen may result in substantial rebound viremia and require a new drug regimen. The use of virus genotyping or phenotyping to identify drugs likely to be active in an anti-retroviral experienced patient is now recommended, but these tests have limitations and their clinical utility has not yet been established. The goal of this project is to investigate the correlation between phenotype/genotype to selected antiretroviral agents and short-term change in viral load upon discontinuation of a single antiretroviral agent from a failing regimen. For the nucleoside reverse transcriptase inhibitors (NRTIs) and the protease inhibitors, resistance is poorly understood; thus, we plan to determine whether a change in viral load occurs after discontinuing these drugs. If so, we plan to correlate those changes with phenotypic and genotypic characteristics. Study participants must have a stable viral load of at least 1000 copies/ml by bDNA assay despite HAART and must be receiving one of the anti-retroviral agents designated for study:. Baseline viral load will be established by multiple bDNA sampling over a 10-day period. Next, the drug of interest will be withdrawn and the rest of the regimen maintained for either a two week (NRTIs except 3TC, protease inhibitor) or four week (3TC) discontinuation to assess for change in viral load. Finally, the withdrawn agent will be re-instituted, and serial sampling for change in viral load, genotype or phenotype will follow.
- Conditions
- HIV Infection
- Keywords
- AIDS, Antiretroviral Therapy, Drug Resistance, Phenotype, HIV, Genotype, Treatment Experienced
- Medical subject headings
- HIV Infections, Acquired Immunodeficiency Syndrome
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Nov 2000 (estimated)
- Study start7 Nov 2000
- Study completion6 Sep 2011
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 InfectionStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)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
- Observational
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00006494
- Sponsor's protocol ID
- 010004
- Other IDs
- 01-I-0004
- Status last verified
- 6 Sep 2011
- First submitted
- 14 Nov 2000
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
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.
PubMed 10397555Lucas 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.
PubMed 10419445Hirsch 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.
PubMed 10815085
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT00006494
- Acronym / sponsor ID
- 010004
- Conditions
- HIV Infection
- Keywords
- AIDS, Antiretroviral Therapy, Drug Resistance, Phenotype, HIV, Genotype, Treatment Experienced
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 7 Nov 2000
- Study completion
- 6 Sep 2011
- First posted
- 15 Nov 2000 (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.
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...
Detailed description
The efficacy of highly active antiretroviral therapy (HAART) is limited by the emergence of drug-resistant virus strains. Development of resistance to one or more antiretroviral drugs in a HAART regimen may result in substantial rebound viremia and require a new drug regimen. The use of virus genotyping or phenotyping to identify drugs likely to be active in an anti-retroviral experienced patient is now recommended, but these tests have limitations and their clinical utility has not yet been established. The goal of this project is to investigate the correlation between phenotype/genotype to selected antiretroviral agents and short-term change in viral load upon discontinuation of a single antiretroviral agent from a failing regimen. For the nucleoside reverse transcriptase inhibitors (NRTIs) and the protease inhibitors, resistance is poorly understood; thus, we plan to determine whether a change in viral load occurs after discontinuing these drugs. If so, we plan to correlate those changes with phenotypic and genotypic characteristics. Study participants must have a stable viral load of at least 1000 copies/ml by bDNA assay despite HAART and must be receiving one of the anti-retroviral agents designated for study:. Baseline viral load will be established by multiple bDNA sampling over a 10-day period. Next, the drug of interest will be withdrawn and the rest of the regimen maintained for either a two week (NRTIs except 3TC, protease inhibitor) or four week (3TC) discontinuation to assess for change in viral load. Finally, the withdrawn agent will be re-instituted, and serial sampling for change in viral load, genotype or phenotype will follow.
Study design
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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.
Key exclusion criteria (15 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
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 2 Jul 2017.
- Background: PubMed 10397555Deeks 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.
- Background: PubMed 10419445Lucas 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.
- Background: PubMed 10815085Hirsch 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.
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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.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of HIV Infection, run by National Institute of Allergy and Infectious Diseases (NIAID) at 2 sites 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 11 inclusion and 15 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 2 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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.
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 NCT00006494, 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 2 Jul 2017.