Intermittent vs. Continuous HAART to Treat Chronic HIV Infection
This study will evaluate the effects of intermittent short cycles of HAART (highly active antiretroviral therapy) for treating HIV infection. HAART is a multi-drug regimen that is very effective in suppressing HIV and perhaps slowing or halting progression to AIDS. However, the treatment has significant drawbacks: it cannot completely rid the body of virus; long-term therapy carries a risk of toxicity (harmful side effects); and the regimen is difficult to comply with because many pills and capsules must be taken daily. When patients stop taking HAART, their HIV levels climb again. This study will see if giving HAART in short cycles of 7 days on, 7 days off, can keep viral levels low while maintaining CD4+ T cell counts.
HIV-infected people age 18 or older who are receiving HAART and have a viral load of less than 50 copies/ml and a CD4+ T cell count of at least 175 cells/mm3 may be eligible for this study. Candidates will be screened with a medical history and physical examination, blood and urine tests, and possibly a chest X-ray and electrocardiogram. Women of childbearing potential will have a pregnancy test.
Participants will be randomly assigned to either continue their current medication regimen or to take HAART in intermittent cycles of 7 days off, 7 days on. Patients will continue treatment for 72 weeks or until viral levels increase or CD4+ T cell counts decline to a level of concern.
Upon entering the study, patients will have blood tests to monitor the amount of virus in the blood, CD4+ T cell count, viral resistance to HAART medications, side effects of the drug, and immune response to HIV in the test tube. They will have clinic visits for a history, physical examination and blood draws every month for 12 months. At that time, depending on T cell counts and viral load, the number of visits may be reduced, but never less frequently than every other month.
Patients will also undergo leukapheresis-a procedure for collecting quantities of white blood cells-every 3 to 4 months while on the study. For this procedure, whole blood is collected through a needle in an arm vein (similar to donating blood). The blood is circulated through a cell separator where the white cells are removed, and the rest of the blood (plasma, red cells and platelets) is returned through the same needle or through a second one in the other arm. The collected white cells are used for special studies on the level and function of T cells and to detect hidden virus.
|Study Design:||Endpoint Classification: Efficacy Study
Primary Purpose: Treatment
|Official Title:||A Randomized, Controlled Trial of Short Cycle Intermittent Versus Continuous HAART for the Treatment of Chronic HIV Infection|
|Study Start Date:||October 2001|
|Estimated Study Completion Date:||January 2005|
Although highly active antiretroviral therapy (HAART) has been successful in suppressing plasma HIV RNA levels in infected patients, it has not resulted in eradication of virus. It is now clear that virus replication persists despite undetectable plasma viremia in individuals receiving HAART. In this regard, withdrawing HAART, even after prolonged periods of virus suppression, leads to an almost universal rapid rebound of plasma viremia. It is also now clear that prolonged, continuous HAART carries a risk of significant toxicity and side effects. In addition, the monetary cost of HAART is prohibitive for many individuals and countries. These recent observations may argue for a different approach to HAART with the goals of : 1) durable suppression of virus replication, without an attempt at eradication, 2) minimization of toxicity and side effects and improvement in patient life-style, and 3) a reduction in cost. Therefore, we propose to study the virologic and immunologic effects of short cycle intermittent versus continuous HAART in HIV-infected individuals as a possible means to achieve these goals. In a pilot study of patients successfully treated with HAART, we have demonstrated that cycles of 7 days on HAART followed by 7 days off HAART can maintain suppression of plasma, lymph node, and resting CD4+ T cell HIV while maintaining CD4+ T cell counts for up to 1 year. It is the purpose of this study to further evaluate these observations with a randomized, controlled, intent-to-treat trial.
|United States, Maryland|
|National Institute of Allergy and Infectious Diseases (NIAID)|
|Bethesda, Maryland, United States, 20892|