Cellular dysmetabolism: the dark side of HIV-1 infection

The progression to disease in subjects infected with the human immunodeficiency virus type I (HIV-1) cannot be explained solely on the basis of the infecting HIV-1 species. There is recent evidence that abnormalities in the cellular metabolism are crucial to the progression of the infection through common pathways that involve the induction of apoptosis and oxidant stress. Conversely, the low propensity of lymphocytes to undergo apoptosis, a normal redox status, and a balanced ceramide metabolism appear to predict a slow progression, or the non-progression at all, of the infection. It is likely that the ability of the host to maintain over time a balanced cellular metabolism despite the chronic infection with the virus contributes to the especially favourable outcome of an otherwise fatal infection seen in a discrete subgroup of HIV-1-infected individuals (long-term non-progressors) who might never experience any of the adverse effects of HIV-1 infection and will never demonstrate disease progression. Furthermore, this background supports the hypothesis that adjunctive therapies directed at correcting certain abnormalities of cellular metabolism seen in the infected host should be given in combination with antiretroviral drugs in order to slow the progression of the infection.