HIV RNA suppression and immune restoration: can we do better?

HAART has significantly changed the natural history of HIV infection: patientsreceiving antiretrovirals are usually able to control viremia, even though notall virological responders adequately recover their CD4+ count. The reasons forpoor immune restoration are only partially known and they include genetic,demographic and immunologic factors. A crucial element affecting immune recovery is immune activation, related to residual viremia; indeed, a suboptimalvirological control (i.e., low levels of plasma HIV RNA) has been related withhigher levels of chronic inflammation and all-cause mortality. The sources ofresidual viremia are not yet completely known, even though the most important oneis represented by latently infected cells. Several methods, including 2-LTR HIVDNA and unspliced HIV RNA measurement, have been developed to estimate residualviremia and predict the outcome of antiretroviral therapy. Considering that poor immunologic responders are exposed to a higher risk of both AIDS-related andnon-AIDS-related diseases, there is a need of new therapeutic strategies,including immunomodulators and drugs targeting the latent viral reservoirs, inorder to face residual viremia but also to "drive" the host immunologicresponses.