7.1.1 When to start ART in adults and adolescents

Consolidated ARV guidelines, June 2013

Clinical considerations and key research gaps

Clinical considerations

Section 10.6 (Checklist 10.3) discusses implementation considerations for moving the CD4 threshold from 350 cells/mm3 to 500 cells/mm3 of relevance to programme managers.

Key research gaps

Further research is required to determine more fully the clinical benefits and disadvantages of earlier ART initiation. Two large randomized trials are examining the optimal timing for initiating ART, with results expected in 2014 to 2015. The Strategic Timing of Antiretroviral Therapy (START) trial in ARV-naive adults aged 18 years and older is comparing immediate ART in those with CD4 cell counts above 500 cells/mm3 to ART deferred until the CD4 count falls below 350 cells/mm3 or an AIDS event develops (80).

The TEMPRANO trial (Early Antiretroviral Treatment and/or Early Isoniazid Prophylaxis against Tuberculosis in HIV-infected Adults – ANRS 12136) is comparing the benefits and risks of initiating ART according to the 2010 WHO guidelines (≤350 cells/mm3) (2) to the benefits and risks of initiating ART immediately among adults with CD4 counts >350 cells/mm3 in Côte d’Ivoire (81). These studies will inform future WHO recommendations.

Other research priorities include assessing the incidence of severe adverse events as a result of increased exposure to ART and assessing ART acceptability, uptake, adherence and long-term retention in care for people who initiate ART at higher CD4 counts, and the magnitude of the prevention benefit of immediately initiating ART in key populations.