The Long and Winding Road Towards an HIV Cure

In the summer of 1981, a new deadly disease suddenly emerged targeting young men having sexwith men (MSM); three years later, a new virus, an exogenous human retrovirus, later named humanimmunodeficiency virus (HIV), was demonstrated to be the causative agent of the new disease, theAcquired Immuno-Deficiency Syndrome (AIDS), affecting, in addition to MSM, also intravenousdrug users, hemophiliacs, heterosexual individuals and children born to infected mothers. AIDSremained a dead sentence for >95% infected individuals until 1996 when the first combinationantiretroviral therapy (cART) was shown to be effective saving the lives of countless people. Sincethen, cART has become extremely powerful and simpler to adhere (now down to one or two pillsa day). However, virus eradication ("Cure") has been achieved thus far only in two individuals asa result of stem cell transplantation by an immunologically compatible donor homozygote for theCCR5Δ32 mutation; CCR5 is indeed the major entry coreceptor for the virus together with theprimary receptor CD4. This represents the exception to the rule that none of the many experimentalattempts of eliminating or silencing the virus reservoir unaffected by cART has achieved a significantproof of concept. In this article we will describe the essential aspects of the viral reservoirs and thecurrent strategies to tackle it.