Cutting Edge Research

Includes Chemotherapy and Transplant Drugs

"There was a time when all the body's members rebelled against the belly," declared a group of men in Shakespeare's Coriolanis, his tumultuous play on democracy. HIV is a democratic invasion of the body that leaves no major organ or system untouched. However, the rebellion against its presence in the lymph node system, and maybe tonsils, has begun.

Cutting-edge research eventually may allow doctors to cleanse HIV reservoirs from the lymph node system, where, after infection, the virus replicates then flushes out into the blood stream. Once circulating in our blood, Highly Active Antiretroviral Therapy (HAART), for some, is effective in reducing viral load and preserving, sometimes increasing, precious CD4 cells. Total eradication of replicating "viral pools" in major body systems is the next logical step.

"We must find ways to eradicate HIV from the body," says Duke University's John A. Bartlett, MD. With assistance from Midge Silberman, RN, Bartlett recently added his tenth human subject to a National Institutes of Health (NIH) clinical trail known as ACTG 380. The study focuses on a potential method of viral eradication: the effects of chemotherapy combined with HAART on HIV DNA present in the lymph node system.

Specifically, Bartlett uses Viracept (nelfinavir) plus Zerit plus Epivir and combines that drug combination with the chemotherapy drug cyclophosphamide in a low-dose regimen. Three chemotherapy treatments are administered (by infusion into a vein) six weeks apart in escalating does. Each infusion requires a 36-hour hospital visit. Investigators want to learn if this particular HAART combination plus cyclophosphamide has any effect on eliminating HIV hidden in lymph nodes, tonsils and blood. Normally, these deep HIV "reservoirs" are not adequately reached by oral HAART regimens alone. All clinical trial subjects must be antiretroviral naïve, according to Bartlett, adding, "That's not always easy to find in patients."

"We're looking to assess if the combined effects of this particular HAART combination when combined with cyclophosphamide can reach those otherwise hard to reach HIV reservoirs," Bartlett says.

HIV and Non-Hodgkin's Lymphoma

Willis Navarro, MD, of the University of California at San Francisco, hopes to use cyclophosphamide and other drugs and existing interventions for different reasons. "I want to apply the standard of care for non-HIV non-Hodgkin's lymphoma patients to HIV positive individuals," he explains.

HIV negative patients who are given a diagnosis of non-Hodgkin's lymphoma and then relapse or are at high risk of relapse are considered as candidates for "autologous stem cell transplant." Stem cells are undeveloped cells that first must be harvested and then transplanted back into patients after they undergo two separate courses of chemotherapy treatments. The "stem cells" will replace bone marrow destroyed by the harsh chemotherapy drugs needed to kill off the lymphoma. Normally, the first-line treatment for this type of lymphoma is chemotherapy alone. The stem cell transplant is a second, more aggressive treatment.

Willis was originally looking for HIV positive patients with a de novo (or new, recent) diagnosis of non-Hodgkin's lymphoma, but after conducting an open study for one year he found only one patient with the needed characteristics. "My referral sources are telling me they don't see as much HIV-related lymphoma as before," he says, possibly due to HAART's general improvements to the immune system. "I'm revising the study to enroll HIV positive patients with existing diagnosis of non-Hodgkin's lymphoma or patients who have relapsed or who are at high risk of relapse," Willis says.

The clinical scenario for treating non-Hodgkin's lymphoma is complicated. Adding HIV creates an even more complex logarithm. The study's first purpose is to see if intensive chemotherapy combined with stem cell transplant is safe and well tolerated by individuals with AIDS-related lymphoma. The treatment itself is not new and is the accepted standard of care for non-HIV, non-Hodgkin's lymphoma.

Viral eradication of HIV through chemotherapy and effective treatments for non-Hodgkin's lymphoma may signal a time when all the body's parts may stop rebelling against the treatments.

Note: For more information on these and other HIV clinical trials, call (800) TRIALS-A.