Mechanisms of T-Cell Depletion and Regeneration in HIV Disease

More than 20 years since the beginning of the aids epidemic, there is still no clear-cut explanation for hiv’s most basic and insidious effect in the human body: the gradual depletion of CD4+ T-lymphocytes in the absence of antiretroviral treatment. At the same time, there is little consensus regarding the mechanism(s) by which CD4+ cell counts improve once therapy is commenced. On some level, the fact that CD4+ cell counts do improve—both quantitatively and qualitatively—with antiretroviral therapy should be enough to satisfy the hearts and minds of hiv-treating clinicians. But there is much to be gained medicinally with the continued exploration of these fundamental questions. For example, antiretroviral therapy plays a critical role in halting the accelerated destruction of CD4+ cells, perhaps the most widely accepted mechanism of hiv-associated CD4+ cell depletion. But there is also at least one other mechanism to ponder—the impaired production of new CD4+ cells as a result of hiv infection—that may have significant bearing on the evaluation and potential use of various immune-based therapies in the clinical management of hiv-positive patients.