Immune and Viral Status of HIV-Infected Patients After Stopping Combination Antiretroviral Therapy
This study will examine the effects of increases in HIV blood levels on the immune system. A better understanding of how HIV alters the immune response may lead to development of effective immune-based therapies against the virus.
Patients 18 years of age or older with HIV-1 infection who have been receiving highly active antiretroviral therapy (HAART) may be eligible for this study. In order to study the effect of increased levels of virus on the immune system, therapy will be stopped in these patients temporarily. Therefore, only patients who have an appropriate level of understanding of the potential benefits of therapy and the risks of stopping treatment will be considered for enrollment. Pregnant women may not participate and women of childbearing potential must agree not to become pregnant during the study. Candidates will be screened with a medical history, physical exam, blood and urine tests and possibly a chest X-ray and electrocardiogram.
Upon entering the study, participants will have blood tests to measure the amount of virus in the blood, CD4+ T cell counts, side effects of the medications, and how the patient s immune system responds to HIV in the test tube. White cells will be collected through leukapheresis. In this procedure, a needle is placed in an arm vein and blood flows from the vein through a tube (catheter) into a cell separator machine, where the white cells are separated from the rest of the blood by a spinning process. Some of the white cells are collected by the machine, and the rest of the blood is returned to the body through a second needle placed in the other arm. Patients will then have a physical examination and blood tests every 1 to 2 weeks and will be managed according to their viral load and CD4 cell counts as follows:
- If viral blood levels remain less than 5000 copies per milliliter, no medical intervention is planned.
- If viral blood levels rise to 5,000 copies per ml or higher, patients will undergo a second leukapheresis and re-start antiretroviral therapy. They will be monitored at least monthly until viral load returns to pre-study levels.
- If the CD4 count rises or remains at pre-study levels, no intervention is planned.
- If the CD4 count decreases by 10 to 25 percent of pre-study levels, the counts will be monitored every 2 weeks at least 3 times and then monthly.
- If the CD4 count decreases by 25 percent or more of pre-study values, antiretroviral therapy will be re-started and counts will be monitored until they return to pre-study levels.
If viral and CD4 levels do not return to pre-study levels promptly, patients will continue to be monitored and will be advised about possible treatment changes. Alternatively, patients whose viral and CD4 levels are similar to or better than pre-study values may be offered laboratory testing every 3 months for at least 1 year if there is a scientific reason to continue studying the patient s immune system. Patients may be asked to undergo additional leukapheresis in the future, or another interruption of therapy in the future if it is felt safe to do so.
|Official Title:||Immunologic and Virologic Characterization of HIV-Infected Patients After Cessation of Highly Active Antiretroviral Therapy (HAART)|
|Study Start Date:||December 1998|
|Estimated Study Completion Date:||April 2013|
Highly active antiretroviral therapy (HAART) has been successful in controlling HIV levels in infected patients, but it is not effective in eliminating the virus from the patient and life-long therapy is thought to be required. However, proper adherence to HAART regimens is costly, results in inconveniences to patients, and is not without significant acute and long-term risks. Many patients are interested in undergoing treatment interruption to relieve these inconveniences and risks. This study seeks to identify these patients and to monitor them for virologic and immunologic parameters during the treatment interruption. Patients that meet the criteria for the study will discontinue all antiretroviral therapy simultaneously, after which the patient will be monitored by a full panel of virologic, immunologic, and safety parameters. Through this study, we will attempt to further characterize the mechanisms by which HIV evades and/or suppresses an effective anti-viral immune response and to identify features of the virus or the patients' immune responses that are associated with virologic control following treatment interruption.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00001899
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Mark Connors, M.D.||National Institute of Allergy and Infectious Diseases (NIAID)|