Evaluation of current strategies to inhibit HIV entry, integration and maturation

Abstract

Human immunodeficiency virus type 1 (HIV-1) infection continues to be a massive global health crisis, particularly in developing countries. With no effective vaccine and no prospect for a cure in the foreseeable future, antiretroviral treatment is the only option at hand to combat HIV infection. Current HIV therapeutics target the viral enzymes reverse transcriptase and protease. The use of a combination of these drugs, termed highly active antiretroviral therapy (HAART), can efficiently reduce viral load in infected patients. Despite the success of HAART in reducing HIV related morbidity and mortality, HAART cannot eradicate virus in infected patients and might not confer life long suppression of HIV replication. In fact, due to ongoing HIV replication, drug resistant viruses frequently arise in treated patients and such viruses are increasingly transmitted between individuals. These observations, together with the considerable side effects of some HAART regimens, underline that current therapeutics need to be improved and that new antiviral agents with novel modes of action that are effective against current drug resistant viruses need to be sought. The replicative cycle of HIV affords multiple opportunities for therapeutic intervention. Entry of HIV into a cell, integration of the viral genome into the host cell chromosome and the generation of mature infectious progeny virions ("maturation") are promising targets for inhibitors. Here, we will discuss how HIV accomplishes entry, integration and maturation and which strategies are being pursued to inhibit these processes.