The science of rapid start—From the when to the how of antiretroviral initiation

Starting antiretroviral therapy (ART) as soon as possible after HIV infection has clear biological and clinical benefits [1].HIV devastates the enteric immune system within days of infection [2], creates chronic inflammation [3], and immunological vulnerabilities to infections such as tuberculosis and bacterial pneumonias emerge even when CD4 levels are high [4].Treatment halts, but cannot fully reverse, this damage.In patients with advanced immunosuppression, accelerating treatment by weeks or days can be lifesaving [5,6].Successful treatment can also virtually eliminate transmission [7,8].Medications continue to become less toxic and more convenient.Clinically, sooner is better.In practice, however, biology depends on behavior.Health systems, healthcare workers, and patients interact to deliver, prescribe, take up, and adhere to medications.HIV diagnosis is a vulnerable time when patients are navigating complicated psychological and social terrains of stigma, threatened relationships, and complex livelihood demands.Offering treatment effectively at this moment requires health systems that are nimble and sensitive.Surprisingly, although studies have found that the introduction of technologies and streamlined clinical operations can minimize delays [9], data are lacking on how to shape what the diagnosis, and the prospect of treatment, means to patients, despite the fact that this meaning is likely to drive subsequent engagement, stabilization, and behavior after HIV diagnosis.Similarly, few data exist for shaping the meaning of illness after diagnoses for other disease conditions (e.g., cancer, diabetes) even though this is of critical importance.The research article by Koenig and colleagues [10] is a critical step toward addressing the knowledge gap about how fast to start ART.Nonpregnant patients who were newly diagnosed with HIV in voluntary testing and counseling were randomized to same-day initiation of ART or initiation after 21 days.Despite an unselected population, only 7 of 821 patients willing to participate were deemed not ready to be randomized to immediate ART through use of a standardized questionnaire, suggesting that many of today's patients perceive treatment with, as the authors suggest, a sense of hope that facilitates treatment initiation.Same-day initiation (compared to starting 21 days later) demonstrated clear benefits in this study: a combined outcome of 12-month retention and viral suppression was 44% in the control but 53% in the intervention, while deaths were 6% and 3%, respectively-both statistically significant.These results extend previous findings.In an individual randomized trial, Rosen and colleagues found rapid ART initiation in South Africa led to a higher proportion of patients initiating ART within 90 days and suppressed at 10 months (51% versus 64%, risk difference: 13%; 95% CI 3% to 23%).In a cluster randomized trial, Amanyire and colleagues showed a multicomponent intervention targeting healthcare workers led to a higher proportion of patients initiating treatment on the same day as clinical eligibility (18% versus 71%, risk difference: