The Use of Leukapheresis to Support HIV Pathogenesis Studies

Despite the dramatic improvements that have resulted from combination antiretroviral
treatment, long-term efficacy, toxicity, cost, and the requirements for life-long adherence
remain as formidable challenges. Also, there is emerging consensus that persistent
HIV-associated disease occurs during long-term highly active antiretroviral therapy (HAART).
This disease may be due to either direct drug-toxicity and/or persistent viral
replication/production and/or persistent HIV-associated inflammation. Hence, strategies aimed
at achieving complete viral eradication may be needed in order to fully restore health among
HIV infected individuals. Even if complete eradication proves impossible—as most believe to
be the case—a less rigorous but still desirable outcome might be achieving durable control of
virus in the absence of therapy. That a "functional" cure is possible is well illustrated by
those rare individuals who are able to durably control replication competent virus in the
absence of therapy ("elite" controllers).

A more complete understanding of the relationship between inflammation and viral persistence
is necessary before more rationale studies of HIV eradication can be designed. Also, a well
validated high through-put virologic assay needs to be developed that can estimate the size
of the latent reservoir. Since the level of replication competent virus in long-term treated
patients (and in elite controllers) is very small (< 1% of CD4 cells harbor HIV), large
numbers of CD4+ T cells most be obtained from study participants in order to routinely
isolate and quantify virus persistence.