The cases of the Berlin and London patients also

The cases of the Berlin and London patients also highlight our limits to defining an HIV cure. No signs of the virus have been found in numerous assays with multiple samples from diverse tissues that Timothy Brown has generously contributed to advance research over the past 12 years. In the case of the London patient, HIV-1 RNA has been undetectable at less than 1 copy per milliliter of plasma, and HIV-1 DNA was undetectable in blood CD4 T cells. Quantitative viral outgrowth assays using a total of 24 million resting CD4 T Guanethidine Sulfate were negative. However, the presence of the virus in tissues from this patient remains unexplored. One HIV-infected child, deceased from graft-versus-host disease after transplantation with cells from a / donor, showed undetectable virus post-transplantation in the blood although the virus was readily detected in multiple tissues . In most cases, tests similar to those used to characterize the Berlin and London patients have failed to detect the virus during cART treatment, and even for several months after cART discontinuation in allo-HSCT patients with viral relapse . Ultimately, only treatment interruption may reveal whether remission is achieved or not. Because only 19 months have passed after cART interruption in the London patient, it is premature to conclude that this patient has been cured. Moreover, will the duration of the off-treatment period be sufficient to cross the gap between remission and cure? Some individuals – natural controllers and post-treatment controllers – are able to maintain undetectable viremia for decades . Although in most of these controllers viral DNA is still readily detectable in the blood, in some cases the control is very stringent (with undetectable viremia at the single-copy level); they can display weakly reactive or negative western blots for anti-HIV antibodies, and some patients experience a progressive decline in cell-associated HIV-1 DNA and virus-producing cells, ultimately reaching undetectable blood titers in standard assays , . Therefore, defining which individuals are cured or in remission remains a difficult task, and the road ahead towards finally attaining a scalable HIV cure remains uncertain. Acknowledgments A.S-C. is an investigator in the ICISTEM consortium, which is supported by amfAR. A.S-C. and M.M-T. receive grants from the French Agency of HIV/AIDS Research (ANRS), Sidaction, and MSDAVENIR.