When to start ART in Africa--an urgent research priority.

n engl j med nejm.org 1 ceived lifesaving ART over the past decade, yet in 2011 an estimated 34 million people were living with HIV infection, 6.8 million were eligible for treatment but lacked access to ART, 2.5 million became newly infected, and 1.7 million died of HIVrelated disease.1 Long-standing debate regarding the appropriate timing of ART initiation in the course of HIV infection was recently accentuated by the recognition of the prevention benefit that ART provides by reducing viral load and infectiousness. Mathematical models, ecologic analyses, and results from the HIV Prevention Trials Network (HPTN) study HPTN 052, a randomized, controlled trial that showed reduced HIV transmission from early, as compared with deferred, ART in the infected member of an HIV-discordant couple,2 all stimulated discussion of a “test and treat” approach, whereby all HIV-infected persons would initiate ART immediately after their HIV diagnosis, with anticipated reductions in transmission. A fundamental question remaining is what is best for the health of the HIV-infected people who would take therapy for prevention, especially those in sub-Saharan Africa. In the mid 1990s, we gained a clearer understanding of HIV replication and pathogenesis, viralload testing, and protease inhibitors, and studies showed the efficacy of triple ART in patients with HIV disease. “Hit early, hit hard” was a prevailing theme reflected in U.S. guidelines. Early therapeutic aggressiveness and optimism, however, became tempered by concerns about side effects and drug resistance, and the pendulum swung back toward guidelines more strongly supported by evidence from clinical trials and rigorous evaluations (see figure). For the first 6 years of this century, the Department of Health and Human Services (DHHS) recommended — on the basis of clinical-trial evidence — that ART be initiated when the CD4+ count dropped to less than 200 cells per cubic millimeter. As more durable and patient-friendly therapies were developed, this threshold was progressively raised and, largely on the basis of expert opinion, the 2012 DHHS guidelines essentially advocate treatment for anyone living with HIV infection.3 There is strong evidence and agreement that patients with CD4+ When to Start ART in Africa — An Urgent Research Priority