Elite controllers and lessons learned for HIV-1 cure

Following the success of HIV-1 antiviral treatment that maintains undetectable levels of viral replication and lack of clinical progression, the design of an HIV-1 cure for patients became the next objective. The success of the treated individuals together with the identification of subjects that spontaneously control the clinical progression for long periods, such as long-term non-progressors (LTNPs) and particularly LTNP Elite Controllers (LTNP EC) have shed hope for the feasibility of a potential cure. Although a successful cure has not been attained yet, these patients have provided critical information on the mechanisms involved in the clinical control such as host genetic factors, as well as strong immune responses against the virus. Less attention has been paid to virological factors, particularly the association of the genetic variability and the control of viral infection. Considering all these studies, it has become clear that a combination of several host, immune and viral factors is needed to attain control of the viral replication control and the non-progressor clinical phenotype. Because this control can be reached through different combinations of factors, this group of individuals is not homogenous. As HIV-1 cure has been shown to be extremely difficult to achieve, a more feasible objective is the functional cure of the viral infection. After the analysis of multiple studies on the mechanisms of control in LTNP EC, we found subjects with various host protective factors and prolonged viral control. These subjects present a complete lack of evolution after more than 20-30 years of infection, stable levels of CD4+ cells (>400-500 cells/μl), a strong immune response, and no signs of clinical progression. We propose that individuals with these characteristics could have attained a functional cure of the HIV-1 infection.