The progression towards AIDS in HIV-1-infected individuals appears to be directly related to CD4 cell count decline and HIV-1 viral loads in the plasma and lymphoid tissues [1]. Though several factors account for the wide variations in HIV-1 disease progression, immune activation is probably the most important determinant for these differences. Activation of host immune cells (primarily CD4 cells, macrophages and dendritic cells) facilitates multiple steps of the viral life cycle and cellular factors that are directly or indirectly connected with it. These include up-regulation of the viral co-receptors (CCR5 and CXCR4), decreased âchemokine secretion [2], enhanced viral entry and integration as well as viral assembly and/or release [3]. Immune activation also leads to profound changes in the cytokine network, with increased secretion of tumor necrosis factor-alpha (TNF-á), interleukin (IL)-2, IL-4, IL-6 and IL-10, and affects the cell cycle [4, 5]. Immune activation is also associated with various degrees of immune dysfunction, hyporesponsiveness and apoptosis, all leading to enhanced progression of immune deficiency and decreased survival [6±11]. Thus, since all concurrent infections, whether systemic or local, will lead to various degrees of immune activation in vivo, it is plausible that they may enhance HIV infection, increase HIV replication and viral load, and accelerate the progression of disease [12±14](Fig. 1).

Several features of the AIDS epidemic in Africa mark it as a distinctive entity in comparison to that in other areas of the world. It seems that HIV is transmitted more easily, the clinical manifestations are quite different and its progression is faster,[15±19]. However, the issue of progression is not confirmed, due to lack of sufficient controlled studies [20, 21]. The above-cited features are probably responsible for the catastrophic dimensions of the epidemic in Africa and Southeast Asia where the prevalence of the infection in adults has reached 30% or more [22]. We have suggested previously that chronic immune activation of the host, by helminthic and probably also by other infections, may account, at least in part, for these dramatic differences in the behavior of the epidemic [23, 24]. The immune activation, we argued, makes the host more susceptible to HIV infection and less capable of handling the infection once it is acquired. We have accumulated several lines of evidence that lend support to these general ideas [25±31]. A large number of clinical observations have indicated that the presence of con-