The Long and Winding Road Towards an HIV Cure

In the summer of 1981, a new deadly disease suddenly emerged targeting young men having sex with men (MSM); three years later, a new virus, an exogenous human retrovirus, later named human immunodeficiency virus (HIV), was demonstrated to be the causative agent of the new disease, the Acquired Immuno-Deficiency Syndrome (AIDS), affecting, in addition to MSM, also intravenous drug users, hemophiliacs, heterosexual individuals and children born to infected mothers. AIDS remained a dead sentence for >95% infected individuals until 1996 when the first combination antiretroviral therapy (cART) was shown to be effective saving the lives of countless people. Since then, cART has become extremely powerful and simpler to adhere (now down to one or two pills a day). However, virus eradication (Cure) has been achieved thus far only in two individuals as a result of stem cell transplantation by an immunologically compatible donor homozygote for the CCR5 Delta 32 mutation; CCR5 is indeed the major entry coreceptor for the virus together with the primary receptor CD4. This represents the exception to the rule that none of the many experimental attempts of eliminating or silencing the virus reservoir unaffected by cART has achieved a significant proof of concept. In this article we will describe the essential aspects of the viral reservoirs and the current strategies to tackle it.

Automated summary

In the summer of 1981, a new deadly disease called AIDS emerged, affecting various populations. The first combination antiretroviral therapy (cART) in 1996 saved countless lives. However, complete eradication of the virus has only been achieved in two individuals through stem cell transplantation.