Two broadly defined categories of a cure for HIV infection exist—a functional cure and a sterilising cure. A functional cure is defined as host-mediated control of HIV replication, in the absence of ART. A functional cure suppresses viral replication for a pre-defined period of time (eg, 5 years) in the absence of treatment, restores and stabilises effective immune function, and decreases both HIV-induced inflammation (which could increase the risk of AIDS or non-AIDS morbidity) and in those individuals that maintain stable low-level plasma viral loads, reduces the risk of virus transmission to others. A functional cure is achieved spontaneously by a rare group of individuals who naturally control HIV replication without treatment (so-called elite controllers). These patients are characterised by a favourable HLA profile and potent HIV-specific CD8 T-cell responses that are associated with a low viral DNA reservoir. In 2010, a second group of patients who initiated ART during acute infection, and controlled HIV for several years after interruption of ART was identified.1 These so-called post-treatment controllers are very rare, and unlike elite controllers, do not show strong HIV-specific CD8 T cell responses or have protective HLA alleles.2 and 3
A sterilising cure needs the complete elimination of replication-competent virus. Complete elimination of virus was probably first achieved after myeloablative chemotherapy, whole-body irradiation, and successful transplantation of haemopoietic stem cells from a CCR5 delta32 homozygous donor into an HIV-infected individual with acute myelogenous leukaemia (the so-called Berlin patient).4 and 5 In a recent report6 from Boston, USA, two patients with relapsed Hodgkin's lymphoma treated with ART who received a CCR5+/+ haemopoietic stem-cell transplant, had undetectable pro-viral DNA and replication-competent HIV 8–17 months after transplantation. These findings suggest that ablative conditioning, immunosuppressive treatment, and post-transplant graft-versus-host disease—all of which were common in the Berlin patient and the Boston cases—might cause substantial and perhaps curative reductions in the size of the reservoir.6 To establish whether the Boston individuals were truly cured, ART will need to be interrupted. Efforts to pursue both functional and sterilising cures are in progress. An effective cure might need a combination of approaches For example, attempts to eradicate the reservoir might not work unless the capacity of the immune system to clear and control the virus is enhanced.