• Thymic Reconstitution in Primary HIV Infection (PHI) following HAART Is Polyclonal (Poster 409)
  Authored by J. F. Poulin, R. Cheynier, M. Sylvestre, R. P. Sekaly, C. Tsoukas, P. M. Girard, J. Modai, S. Kinloch, B. Gazzard, L. Perrin, L. Goh, S. Pratt, and J. Lambert
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There is a great deal of work on identifying and treating the earliest forms of HIV infection principally within two weeks of exposure. There is often no identifiable HIV antibody response and a diagnosis is based on history and symptoms often without accompanying blood work. There may be some evidence of HIV in the blood through sophisticated tests, but early identification through recognition is the key to identifying a very recent exposure and the transition to becoming HIV positive. There has been much thought and hope that early treatment of these individuals might prevent the subsequent decline in immune function and loss of certain types of HIV-specific immune cells that are helpful in preventing immune decline. There were a number of papers examining this theory, Markowitz (abstract 288) reported no subsequent control after cessation of therapy for 2.5 to 5 years in PHI, but Bruce Walker, presenting his work at Mass General Hospital, reported significant immunologic control of HIV after differing amounts of antiviral therapy and subsequent termination of treatment. The overall clinical utility of this aggressive early intervention is currently under great scrutiny.

The mechanism for this prevention of immune decline is being studied and investigators are seeking links in the physiology of immune prevention and control of HIV to explain these emerging clinical studies. Poulin's study looked at the response of the immune system to primary HIV infection (PHI) and specifically the role of the thymus, an important small gland in the neck that is the factory site for developing and processing many immune responses and is quite prominent in childhood and smaller in adulthood. They found that with early treatment with a potent HIV regimen (Combivir, amprenavir, and abacavir) there was a significant and broad production of T cells. The diversity and breadth of this production as well as the amount ranged from 5- to 50-fold higher in 67% of patients treated early in PHI compared to patients treated later in a more chronically infected situation. Poulin et al. feel this reflects that early treatment prevented the decline in thymic function and thus resulted in a more functional immunologic response if patients were treated before the decline could begin.

This is an important step in establishing the mechanism for the possible benefit of early treatment after HIV exposure. There is a growing body of literature that is supportive of aggressive treatment so early after exposure with the hope that we can permanently alter the subsequent immune response and prevent immune deterioration. It is very difficult to recognize these early symptoms of a flu-like illness after an exposure and the long term clinical benefit of this intervention will depend on early identification, education, and rapid access. This could be more difficult to achieve than the research supporting the intervention.