Natural Resistance to HIV Infection: Lessons Learned from HIV-Exposed Uninfected Individuals

Abstract

We explored potential mechanisms of resistance to human immunodeficiency virus type 1 (HIV-1) infection in different groups of uninfected individuals exposed by systemic or mucosal routes: intravascular drug users in Vietnam and spouses of HIV-infected individuals in Cambodia and Central African Republic. Our main findings were reduced susceptibility of peripheral blood mononuclear cells to HIV-1 infection in vitro, associated with low levels of CD4⁺ T cell activation in vivo and/or cell restriction of viral replication, and enhanced natural killer cell activity, associated with increased ratios of activating to inhibitory natural killer cell receptors. These results support a contribution of innate responses to resistance against HIV-1 infection. Scientific and ethical issues encountered during research in exposed uninfected subjects must be considered.