Thinking about an AIDS end game.

1462 www.thelancet.com Vol 382 November 2, 2013 Scientifi c inquiry can be guided, and misguided, by past experience. When confronted with the emerging AIDS epidemic in the early 1980s, some scientists and clinicians thought of hepatitis B as a model for how to approach understanding and solving the challenges posed by the burgeoning number of immunodefi ciency cases. Hepatitis B was transmissible by blood and anogenital secretions, similar to the patterns of spread noted with the yet-to-be-defi ned pathogen. In the previous decade, researchers had identifi ed hepatitis B’s epidemiology, found that surface antibody titres correlated with protection, learned how to diagnose diff erent stages of infection, and developed a highly protective vaccine. Thus, when Jerome Groopman and I sent a panel of blood specimens from asymptomatic men who have sex with men who were partners of patients with AIDS to Robert Gallo’s laboratory in late 1983, and were subsequently informed that 21% tested positive for HTLV-III, we were left with the quandary of what we would tell those who tested positive. At the time, our counselling messages included the hope that some of the men might have developed immunity and would not get sick. Subsequent follow-up showed a disease with a savage natural history, with most men who were infected with the renamed virus HIV getting sick and dying. The grim reality of the fi rst 15 years of the epidemic was replaced by new-found therapeutic optimism once partially eff ective drugs were tested in combination, and treatment responses could be monitored by recently developed nucleic acid amplifi cation technology, creating a new regimen of highly active antiretroviral therapy (HAART) to suppress plasma viraemia. Excitement about Thinking about an AIDS end game the steps from diagnosis to retention in care and successful treatment. In some regions, discrimination, stigma, and legal barriers impede the realisation of optimum care. These impediments must be addressed. Furthermore, longer-acting therapies could improve adherence to pre-exposure prophylaxis and treatment. Understanding of co-infections such as tuberculosis and hepatitis B and C; chronic comorbidities including atherosclerosis, some cancers, liver and kidney disease, and neurocognitive prob lems; and th e ageing process—is also crucial. Finally, a cure for HIV infection is no longer beyond the imagination, and eff orts are aimed at either eradication of HIV in infected individuals or indefi nite control of viral replication in the absence of ART, referred to as a functional cure. To realise the potential of these eff orts, along with those directed at vaccine development and new treatments, translation of con cepts into interventions will prove essential. A range of highly eff ective HIV treatment and preven tion methods is available, and others are under intensive investigation through basic and translational research. By combining eff ective implementation of existing methods with the discovery and eventual introduction of new interventions, achieving an AIDSfree world is no longer an idealistic aspiration—it is an achievable goal (fi gure). *Anthony S Fauci, Hilary D Marston National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-2520, USA [email protected]