Restored Immunity Protects Aids Patients From Opportunistic Infection

A new study led by a Columbia researcher demonstrates that HIV-infected patients who respond well to antiretroviral drugs can safely forgo antibiotics to prevent certain opportunistic infections. Dr. Wafaa M. El-Sadr, chief of the Division of Infectious Disease at the Harlem Hospital Center and a professor of clinical medicine at Columbia University’s College of Physicians & Surgeons, led the study, which included patients at 15 centers nationwide. The report of the study will appear in the April 13 issue of the New England Journal of Medicine. According to U.S. Public Health Service guidelines, HIV-infected patients with CD4+ cell counts below 50 per cubic millimeter of blood should have antibiotic treatment to prevent Mycobacterium avium complex (MAC) disease, a serious and potentially fatal condition. CD4+ cells are immune system cells that fight infection and are attacked by the HIV virus. Levels of these cells are a measure of the strength of a person’s immune system and the severity of HIV infection. Dr. El-Sadr and her colleagues launched the study to determine whether prophylaxis is still necessary for HIV patients whose CD4+ cell counts rise above 100 per cubic millimeter after treatment with antiretroviral therapy. The researchers enrolled 520 patients with a median CD4+ cell count of 230 per cubic millimeter of blood. All of the study participants had CD4+ levels below 50 at some point in the past but had two consecutive CD4+ cell counts of 100 or more since beginning antiretroviral therapy. Half of the patients took azithromycin each week, while half took a placebo. Patients were followed for an average of 12.7 months. None developed MAC disease during the study. Three patients taking azithromycin and five patients taking the placebo developed bacterial pneumonia. During the study, 19 patients taking azithromycin and three of the patients in the placebo group dropped out because of adverse effects of the drug. Dr. El-Sadr and colleagues describe several benefits that would result from allowing this group of HIV-infected patients to defer taking prophylactic antibiotics. Studies have shown that people who take antibiotics regularly are more likely to develop infections with antibiotic-resistant bacteria. Also, patients on antiretroviral therapy for HIV infection already take several drugs, and adding one more to the regimen increases the risk of drug interaction and also makes following treatment more difficult. Infectious disease and immunology experts had questioned whether CD4+ cells reconstituted by antiretroviral therapy would be as protective against infection as normal CD4+ cells. This study suggests that antiretroviral therapy does reconstitute protective immunity, according to Dr. El-Sadr. “The event rate for all opportunistic infections was actually pretty low across the board,” she explains. “The lower event rate suggests that these individuals are protected against these complications.” The study was funded by a grant from the National Institute of Allergy and Infectious Diseases. “Our study results are promising as they provide a foundation for evaluating drugs that could slow down the progression of ALS,” says Dr. Friedlander, senior author of the study. “Although much more research needs to be conducted in this area, our research does bring us one step closer to finding a treatment for this tragic disease.” ALS is characterized by progressive loss of the motor neurons in the brain, brainstem, and spinal cord. On average, people who develop ALS die within five years of contracting the disease. Roughly 10 percent to 20 percent of ALS cases are hereditary.

All of the mice in the study were implanted with osmotic pumps that delivered zVAD-fmk, or a placebo, into the ventricles of the brain. They received the pumps at 60 days old, when the symptoms of the disease had not yet appeared, and received zVAD-fmk or placebo continuously for 56 days. The motor function of the mice was measured by timing how long they were able to stay on a rotating treadmill-like device called a Rotarod at a certain speed. The mice who received the highest doses of zVAD-fmk survived for an average of 153 days, as compared with 126 days for their untreated littermates, and were symptom-free for 20 days longer, on average.

The research was funded by the National Institute for Neurological Disorders and Stroke, the Muscular Dystrophy Association, the ALS Association, and Project ALS.