HIV Expression in Patients With Low Viral Load on Highly Active Antiretroviral Therapy (HAART)
|First Received Date ICMJE||August 9, 2002|
|Last Updated Date||May 3, 2013|
|Start Date ICMJE||July 2002|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE||Not Provided|
|Original Primary Outcome Measures ICMJE||Not Provided|
|Change History||Complete list of historical versions of study NCT00043641 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE||Not Provided|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||HIV Expression in Patients With Low Viral Load on Highly Active Antiretroviral Therapy (HAART)|
|Official Title ICMJE||HIV Expression in Patients With Viral Loads Suppressed on HAART|
This study will investigate low-level viral loads in HIV-infected patients taking highly active antiretroviral therapy (HAART). Although HAART reduces viral levels and restores immune function to some degree, it does not cure HIV infection. The virus persists even at levels below that which it can be detected. This study will examine where this residual virus comes from in order to better understand the infection and the effectiveness of therapies. In addition, the study will 1) evaluate the ability of a new test to detect the virus at low levels; and 2) determine whether adding the protease inhibitor Kaletra to the HAART treatment regimen for patients with a low viral load will further decrease their viral load.
HIV-infected patients 18 years of age and older may be eligible for this study. Patients involved in the viral load test will be recruited from an NIAID HIV study in which they are already participating. Three groups of patients will be enrolled: those with a viral load of less than 50 copies/ml plasma, those with 51-500 copies/ml, and those with 501-5000 copies/ml. Patients involved in the Kaletra trial must have been taking HAART for 6 months or more and have less than 50 viral copies/ml plasma. They will be screened for this study with a history, physical examination, and routine laboratory tests.
Participants in the viral load test evaluation will donate 70 ml of blood up to four times. No more than one sample will be collected per day.
Participants in the Kaletra trial will have blood samples drawn on two successive days and will then be randomly assigned to one of two treatment groups. One group will begin Kaletra therapy (four capsules two times a day) immediately; the other will undergo observation for 4 weeks before starting Kaletra. Depending on what group they are in, patients will provide blood samples for viral load measurements and clinical samples according to the following schedule:
One sample each during weeks 1, 2, and 3, of therapy and two samples during week 4.
One sample each during weeks 1, 2, and 3 of observation and two samples during week 4. After starting therapy, one sample will be collected each week during weeks 1, 2, and 3 of therapy and two samples during week 4.
In both groups, after the last dose of medicine on day 28, Kaletra therapy will be complete. At the end of therapy, additional blood will be collected for viral sampling as follows: one sample each during weeks 1, 2, and 3, and two samples during week 4 after Kaletra therapy.
This protocol is an exploratory study of HIV expression in patients who are receiving highly active antiviral therapy and who have low viral loads below or near the current limit of detection (50 copies/ml plasma). Recent studies have suggested that patients with suppressed viral loads in this low range have continued HIV expression, but the amount and the origin of this virus remains unknown. The amount of virus expression in plasma is uncertain because the current viral load assays are imprecise in the cutoff range of 50-75 copies/ml plasma. The origin of the HIV found at low viral loads detected is unknown as well; two possible sources of virus include expression from long-lived reservoirs of infected cells, and low level spreading infection to uninfected cells. Determining the origin of HIV expression has clinical importance; currently available HIV drug therapy will have little effect on HIV expression from established reservoirs, but more potent HIV therapy could potentially inhibit a spreading HIV infection.
In this study we plan two principal objectives. First, we will investigate the level of HIV expression in plasma samples at low viral loads using a new HIV load assay with enhanced sensitivity and precision in the viral load range of 1-100 copies. If data from the survey confirms acceptable performance characteristics for this assay we will proceed with stage II of the protocol. In stage II we plan to determine, in several short-term intensification approaches to investigate whether the incorporation of an additional antiretroviral to suppressive HAART regimens ("intensification HAART") will further suppress plasma virus. In a small pilot study, we will plan to intensify regimens for 30 days in a nonrandomized fashion. Secondly, we plan to study patients who are switching medications for preference or mild toxicity. In these patients we will intensify their regimens for 30 days in an overlap fashion, adding the new drug instead of switching medications. After 30 days of drug overlap, we will continue the new drug and discontinue the identified antiretroviral. These initial studies will assist in obtaining initial data and confirming the estimated sample size of a larger, randomized study to rigorously investigate the virologic effects of drug intensification. If these initial proof-of-concept experiments suggest that HIV may be suppressed by intensification HAART, then we plan to expand the study in a larger controlled trial to determine the degree of suppression possible with intensification therapy.
As a secondary objective we will investigate whether it is feasible to study HIV genetic variation in samples from patients with suppressed viral loads using molecular techniques developed to study HIV variation in patients with viral loads greater than 1000 copies/ml plasma (protocol 00-I-0110).
We plan to enroll up to 70 patients in a viral load survey cohort of HIV viral loads, and analyze a series of samples from completed trials of antiretroviral therapy.
|Study Type ICMJE||Observational|
|Study Design ICMJE||Not Provided|
|Target Follow-Up Duration||Not Provided|
|Sampling Method||Not Provided|
|Study Population||Not Provided|
|Condition ICMJE||HIV Infections|
|Intervention ICMJE||Not Provided|
|Study Group/Cohort (s)||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Completion Date||February 2013|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
-Any febrile illness (T greater than 38.0 degrees C) in the 3 weeks prior to blood draw.
VIRAL SURVEY COHORT- M98-863, M97-720, AACTG 5201 SAMPLES (no inclusion/exclusion):
-Samples from patients enrolled in the completed M98-863, M97-720 or AACTG 5201 study.
INCLUSION CRITERIA: PILOT INTENSIFICATION COHORT:
INCLUSION CRITERIA: RANDOMIZED INTENSIFICATION COHORT (NIH, University of Pittsburgh):
For those starting efavirenz, significant depression, which, in the opinion of the investigators, would be significantly worsened by efavirenz.
INCLUSION CRITERIA - DRUG OVERLAP COHORT:
|Ages||18 Years and older|
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Location Countries ICMJE||United States|
|NCT Number ICMJE||NCT00043641|
|Other Study ID Numbers ICMJE||020232, 02-I-0232|
|Has Data Monitoring Committee||Not Provided|
|Responsible Party||Not Provided|
|Study Sponsor ICMJE||National Institute of Allergy and Infectious Diseases (NIAID)|
|Collaborators ICMJE||Not Provided|
|Information Provided By||National Institutes of Health Clinical Center (CC)|
|Verification Date||February 2013|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP