7.1.1 When to start ART in adults and adolescents

Consolidated ARV guidelines, June 2013


Since 2002, WHO guidelines on ART have evolved as the body of evidence to support the earlier initiation of ART has progressively increased (1).

The 2010 WHO guidelines for adults and adolescents (2) recommended initiating ART for all individuals (including pregnant women) with a CD4 count ≤350 cells/mm3 regardless of WHO clinical stage and for those with severe or advanced HIV disease (WHO clinical stages 3 or 4) regardless of CD4 count. This strong recommendation was based on moderate-quality evidence from randomized controlled trials (3,4) and observational studies (5–8) showing that initiating ART at or below this CD4 threshold reduced mortality, disease progression (including TB), vertical HIV transmission and serious adverse events.

Mathematical modelling simulations also suggested that initiating ART earlier could impact on both sexual and vertical HIV transmission if there is high treatment coverage and full adherence (9). For people with active TB disease or HBV coinfection requiring HBV treatment, the 2010 guidelines (2) recommended initiating ART regardless of CD4 cell count.

Global ART coverage for those eligible according to the 2010 recommendations (CD4 ≤350 cells/mm3) had reached 54% – or more than 8 million people – by the end of 2011 (10) , but coverage varies across regions, ranging from 15% to 68% (11). Only 9 lowand middle-income countries have reported coverage exceeding 80%, and 68 countries have reported coverage of less than 50%. Nevertheless, policy changes in countries have been significant. A recent survey in 92 countries (Web Annex) showed that more than 90% had adopted the CD4 threshold for initiating ART of 350 cells/mm3 or less, and several other countries have moved their CD4 threshold above 350 cells/mm3.

The median CD4 count at the time ART is initiated, although increasing, has been far lower than 350 cells/mm3 in almost all settings, including high-income countries (12,13) , and late presentation for treatment is associated with high early mortality rates and poor retention in care (6,14).

Increasing knowledge of HIV status, strengthening links between testing and care and ensuring optimal long-term retention and adherence remain significant challenges in many settings.