The dramatic saga of the acquired immunodeficiency syndrome (AIDS) features an early sense of helplessness and frustration in the face of a mysterious new disease, courage on the part of the afflicted, and the gradual accrual of groundbreaking scientific advances that have brought hope to a formerly desperate situation. This progress began with a series of detailed epidemiologic studies, which were followed by the discovery of the human immunodeficiency virus (HIV) as the causative agent of AIDS, and has culminated in highly effective treatment regimens that have transformed HIV from a near-certain death sentence to a manageable disease. Looking ahead, and considering the spectacular scientific advances that have been made over nearly four decades, it is conceivable that with optimal implementation of available prevention strategies and treatments, the end of HIV/AIDS as a global pandemic will be attainable.
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With the advent of highly effective combination ART in 1996, efforts to counter HIV on both the individual and population levels entered a new era. ART led to dramatic improvements in the health of individual patients with already advanced disease and to prevention of disease progression in those without obvious clinical manifestations of HIV disease. Not only did ART provide a nearly normal life expectancy for most people with HIV who adhered to their treatment regimens, it also eliminated the risk of transmitting the virus to an uninfected sexual partner.5 It became clear that treating people with HIV was a highly effective means of preventing HIV spread. “Treatment as prevention” proved to be a critical addition to the prevention tool kit that also contained measures such as condom use, voluntary medical male circumcision, and screening of the blood supply. Studies of these interventions also provided the critical evidence base for the principle that “undetectable equals untransmittable,” or “U=U,” which has helped reduce some of the external and sometimes self-imposed stigma associated with HIV infection.
A second major advance in using ART to prevent HIV infection was the introduction of preexposure prophylaxis, or PrEP, for at-risk but uninfected people. Numerous studies have led to the conclusion that a once-daily, single-pill PrEP regimen is 99% effective in preventing sexual acquisition of HIV infection by an at-risk uninfected person. This overwhelming evidence resulted in the U.S. Preventive Services Task Force Grade A recommendation that PrEP should be offered to all persons at high risk for acquiring HIV infection.