HIV Burden Unchecked by Antiretroviral Therapy In Early Stage Disease
Antiretroviral therapy has no detectable effect on the amount of HIV, the virus that causes AIDS, in lymphoid tissue or in certain white blood cells of patients with early HIV disease, according to preliminary results from a study by investigators from the National Institute of Allergy and Infectious Diseases (NIAID).
The study is the largest one to date examining the effect of therapy on HIV in lymph nodes, the main reservoir for the virus in infected individuals. Researchers plan to discuss the study Monday, Aug. 8, at the Tenth International Conference on AIDS in Yokohama, Japan.
The study findings also show that antiretroviral therapy during early HIV disease does not affect HIV replication in such cells. However, a combination of zidovudine (AZT) and didanosine (ddI) appeared to decrease viral replication in patients with more advanced HIV disease.
While the combination of the antiretroviral drugs AZT and ddI can prompt a temporary decrease in HIV replication in the lymphoid tissue of infected individuals, the therapy does not appear to affect viral burden," says Anthony S. Fauci, M.D., director of NIAID and coauthor of the study conducted at the institute's Laboratory of Immunoregulation (LIR). "These findings point to our need to continue investigating other promising candidate therapies."
For the study, investigators enrolled 32 HIV-infected patients into four study arms: - no prior therapy and none initiated, - no prior therapy and AZT begun, - prior AZT therapy that was continued or - prior AZT therapy that was continued with ddI added.
Patients receiving AZT and ddI had more advanced HIV disease than those beginning AZT therapy, notes Oren J. Cohen, M.D., lead author of the study and clinical associate in the LIR. While all enrolling patients had counts of more than 250 cells per cubic milliliter of blood (mm3), those participants starting AZT averaged 654 cells/mm3, while patients adding ddI to ongoing AZT therapy averaged 394 cells/mm3. CD4+ T cells are the critical immune system cells infected by HIV.
The scientists collected samples of blood and lymphoid tissue when patients entered the study and again after eight weeks. Using the laboratory techniques DNA and RNA polymerase chain reaction (PCR), the investigators measured HIV replication and frequency of virus, known as viral burden, in the tissue and in certain mononuclear white blood cells that circulate in the body. The researchers also examined the viral distribution and tissue architecture.
HIV burden remained largely unchanged in the patients," explains Dr. Cohen. "In four of the six patients who added ddI to their AZT therapy, HIV replication in the lymphoid tissue decreased, and in five of the six, the amount of virus present in plasma declined."
None of the patients had significant changes in their CD4+ T cell counts. Participants not receiving AZT had no change (664 to 658 cells/mm3). Also, there was no change in patients remaining on AZT (413 to 408 cells/mm3). Patients beginning AZT therapy had an increase from an average of 654 to 804 cells/mm3, and those individuals adding ddI to their AZT therapy had a rise from an average of 394 to 436 cells/mm3. However, these increases are not statistically significant.
None of the patients in the trial had changes in the cellular structure of their lymphoid tissue between biopsies.
Drs. Fauci and Cohen's coauthors include Giuseppe Pantaleo, M.D., Cecilia Graziosi, Ph.D., and Manette Niu, M.D.
NIAID, a component of the National Institutes of Health, also supports investigators and scientific studies at universities, medical schools, hospitals and research institutions in the United States and abroad aimed at preventing, diagnosing and treating such illnesses as AIDS, tuberculosis and asthma as well as allergies. NIH is an agency of the U.S. Public Health Service, U.S. Department of Health and Human Services.Prepared by:
Office of Communications National Institute of Allergy and Infectious Diseases National Institutes of Health Bethesda, MD 20892
Public Health Service U.S. Department of Health and Human Services June 1994