Modeling immune intervention strategies for HIV-1 infection of humans in the macaque model

Abstract

The introduction of potent antiretroviral therapy (ART) has generated hope and prospects in the management of human immunodeficiency virus-1 (HIV-1) infection. Long-term side effects of ART, however, have also indicated the limitations of this approach alone. A decade ago, immune therapy trials in HIV-1-infected individuals were performed in the absence of ART with a gp160-based vaccine [1]. At that time, the notion that the HIV-1 env obtained from lab-adapted strains would be a poor inducer of antibodies able to neutralize primary HIV-1 isolates was in its infancy [2]. Similarly, the importance of cell-mediated immune response in the containment of HIV-1 replication both in acute and chronic infection 3, 4, 5, 6, 7, 8, albeit predictable from other models of viral infection, was not fully appreciated. Here, attempts to model immune intervention in SIVmac251-infected macaques using vaccines able to elicit cell-mediated immune responses will be reviewed.

The introduction of ART has resulted in effective suppression of viral replication and decreased morbidity and mortality of HIV-1-infected individuals [9]. The decreased morbidity appears to be associated with the reconstitution of immune responses to pathogens, such as cytomegalovirus and Epstein-Barr virus 10, 11, 12. However, HIV-1-specific immune responses decline during ART treatment of adults and children 13, 14, 15, 16, 17, perhaps because of a decrease of HIV-1 replication and antigen exposure under ART. The wide use of ART has also resulted in a better appreciation of the limitations of this daily multi-drug combination treatment, such as compliance 18, 19, due to the complexity of treatment and life-threatening side effects after long-term treatment 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30.