• Poster 241: Low Rates of All Opportunistic Infections among Patients with Advanced HIV Disease Responding to Antiretroviral Therapy -- the CPCRA 048 Cohort (Authored by W. Burman, W. El-Sadr, L. Grant, J. Matts, D. Zeh, B. Gallagher, R. Hafner, L. Crane, and F. Gordin. The Terry Beirn Community Programs for Clin. Res. on AIDS)
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Clonal Deletion Theory Disputed in Study, Revises "Hit Hard, Hit Early" Treatment Approach for People with HIV

Since the beginning of the highly active antiretroviral therapy (HAART) era, people with primary HIV infection and their providers have in mostly been opting for immediate initiation of combination therapy, often including use of a protease inhibitor. The decision to initiate early HAART has mostly been premised on the theory that delaying treatment risked permanent loss of key CD4 cells necessary for proper immune system function during primary infection, and that this "clonal deletion" was irreversible when effective HAART was started in people with advanced HIV disease. This approach to treatment was brought into question on the second day of the 7th Conference on Retroviruses and Opportunistic Infections in San Francisco.

In a study conducted by The Terry Beirn Community Programs for Clinical Research on AIDS (see: poster 241) data was presented that confirm broad-based immune reconstitution is not only possible following initiation of HAART among patients with advanced HIV disease, but that such immune reconstitution is common.

Further, successful immune reconstitution is not dependent upon complete viral suppression, and a significant reduction in the appearance of opportunistic infections and stable increases in CD4 counts is seen even in people with detectable viral load. The study findings suggest that the "clonal deletion" theory advanced to promote early intervention with HAART is incorrect, and that key CD4 cells do rebound following HAART even when a person has advanced HIV disease.

The implications of these results for the treatment of primary infection are significant, and were reinforced during the afternoon slide presentation. In his summary of the data on the severe metabolic complications resulting from HAART, William Powderly, M.D. of the Washington University School of Medicine in St. Louis framed the question of when to initiate HAART therapy around the need to reduce drug side affects, which may increase morbidity and mortality. He said, "The question is not whether to hit hard, hit early vs. hit soft, hit late -- but it is 'hit hard, but when?'" He further suggested that the goal of HAART needs to be more than just good viral suppression, and needs to include letting patients, "live long and prosper," borrowing a phrase from the popular TV show Star Trek. The presentations today mark a turning point in the evolution of treatment for people with HIV infection, and bring in to question many of the unsubstantiated assumptions made about the advantages of early intervention with HAART.

Please note: Knowledge about HIV changes rapidly. Note the date of this summary's publication, and before treating patients or employing any therapies described in these materials, verify all information independently. If you are a patient, please consult a doctor or other medical professional before acting on any of the information presented in this summary. For a complete listing of our most recent conference coverage, click here.