Researchers are enrolling patients in the clinical trial which looks at the safety and tolerability of the three-drug treatment, and to see at what "rate" the study subjects achieve undetectable levels of HIV-1 (or complete suppression or replications) in their plasma by serial testing several times throughout the study. Doctors believe that early intervention can preserve immune function, lessen risk of viral transmission, reduce the rate of disease progression and viral mutations, decrease the severity of acute disease, and suppress the initial burst of viral replication and dissemination in the body.
Current guidelines for HIV treatment have patients begin antiretroviral therapy when their CD4+T cell count falls below 350. It may take years before HIV-infected patients get to this stage, according to Dr. Harold Kessler, associate director of Infectious Diseases at Rush, and Dr. Frank Palella, assistant professor of medicine and associate director of the HIV Outpatient Center at Northwestern University Medical School. Kessler and Palella are co-principal investigators on the study.
Patients in the 52 week research study will receive a combination of didanosine, stavudine, and an experimental protease inhibitor. "In this three-drug regimen, two of the medications (didanosine and the protease inhibitor) are taken once a day and stavudine is taken twice a day," says Kessler. "It is a highly potent, very compact regimen, and fewer pills make it easier for the patient."
Patients in the study will receive laboratory evaluations to determine the benefit of this early therapy and its effect on the immune system.
"here is a difference between the two groups of early infected HIV patients we are recruiting," says Kessler. "The very early, acute primary stage of HIV infection is when the virus is detected within six to eight weeks of infection, before the body has developed an antibody response to the infection. HIV would go undiagnosed with just an antibody test. A person may be experiencing flu-like symptoms and may go to the doctor and be misdiagnosed with a viral infection such as influenza, mononucleosis or German measles. And then the symptoms may disappear within a few days to a week."
Those patients in the early stage of HIV may have had an HIV test within the last six months to a year, with a negative result. Yet, when they are re-tested and have a positive result, they may have been infected with the virus up to 140 to 150 days earlier. When trying to identify this group of patients, doctors must undertake an assessment of an individual patient’s risk for HIV infection by asking important questions, including those about sexual activity and intravenous drug use. Patients can participate in the trial and choose not to take the antiretroviral therapy medication, and be followed as an untreated group. "We will follow these patients with early HIV infection and have them undergo the same intensive clinical evaluation and testing as those receiving medication," says Palella. In the past, patients were diagnosed with the disease and monitored. Once their counts fell to a certain level, they began treatment, sometimes years later. In this study, patients begin drug therapy as early as within 7 to 14 days of screening.
According to an earlier study using this approach, preliminary data suggest that treatment of primary HIV infection with combination therapy may have a beneficial effect on laboratory indicators of disease progression as well as clinical outcomes.
As a result, the National Institute of Allergy and Infectious Diseases has set up collaborative sites to study various aspects of the treatment of acute and early HIV infection. Three cities and four sites have been selected: Rush and Northwestern in Chicago, the AIDS Research Consortium, Atlanta and the University of Colorado, Denver.
Kessler believes "Based on what we already know from preliminary studies, greater efforts to identify people at a much earlier stage of HIV infection will have a major impact in the fight against HIV and other infectious diseases."
Patients or doctors wanting to enroll in the study should contact Rush study coordinator Elke Narkiewicz 312-942-5000 ext. 29156, or Northwestern study coordinator Baiba Berzins 312-695-5012