CLINICAL IMPLICATIONS OF HIV DYNAMICS AND DRUG-RESISTANCE IN MACROPHAGES

Macrophages are widely recognized as the second major target of HIV in the body. The cellular characteristics of such vesting cells markedly affect the dynamics of virus lifecycle, that is slower but far more p rolonged that in lymphocytes. In addition, the limited concentrations of endogenous nucleotide pools in macrophages downregulate the enzymat ic activity of reverse transcriptase. As a consequence, both the anti- HIV activity and the development of resistance to antiviral drugs in m acrophages ave substantially different than those found in activated l ymphocytes. These peculiar characteristics of virus replication and ef ficacy of antiviral drugs in macrophages have a natural in vivo counte rpart in extralymphoid tissues, where macrophages account for the majo rity of cells infected by HIV. Furthermore, the replication of HIV in macrophages of testis and central nervous system is far less affected by antiviral drugs than in lymph nodes, because of the presence of nat ural barriers that markedly diminish the concentration of such drugs. For all these reasons, HIV infection of macrophages should be taken in to account in therapeutic strategies aimed to achieve an optimal thera peutic effect in all tissue compartments where the virus hides and rep licates.