Throughout 2009, WHO worked to update the guidelines for Antiretroviral therapy for HIV infection in adults and adolescents: Recommendations for a public health approach through a series of coordinated efforts to review and synthesize new and emerging evidence on the optimal use of ART within a public health approach. This process was based on the preparation GRADE profiles, systematic and targeted reviews, risk-benefit analyses, technical reports and assessments of impact, feasibility and cost.

All evidence documentation prepared for these guidelines is available on the 2009-2010 ART guidelines for adults and adolescents evidence map web page (http://www.who.int/hiv/topics/treatment/evidence3/en/index.html).

Preparatory work included the following:

• GRADE profiles on when to start ART, what to use in first-line and second-line regimens and when to switch to second-line therapy.
• Systematic and targeted reviews on:

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  the management of HIV/hepatitis and HIV/TB coinfection;

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  ART safety, toxicity and teratogenicity;

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  the utility of CD4 count and viral load in monitoring ART;

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  ART failure criteria;

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  third-line ART;

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  interactions between ARVs and opioids, and drugs used for the treatment of tuberculosis (TB), viral hepatitis and malaria.

• Consultations with PLHIV.
• A report on ART adherence.
• A review of current ART guidelines from 26 countries.
• Costing information based on studies of procurement and production of ARVs.
• An impact assessment of the number of patients in need of treatment according to various CD4 count thresholds.
• A feasibility analysis for the introduction of the proposed guidelines in Malawi.

Search strategies employed in the systematic reviews, meta-analyses and GRADE profiles which were conducted by the Cochrane HIV/AIDS group followed methodology described in The Cochrane handbook for systematic reviews of interventions (Version 5.0.2; last updated September 2009, available at http://www.cochrane-handbook.org/.

In reviews where data were not amenable to meta-analysis and/or GRADE profiles, systematic searches, using relevant key words and search strings, were conducted of electronic databases (Medline/Pubmed, Embase, CENTRAL), conference databases (Aegis, AIDSearch, NLM Gateway and hand searches) and clinical trial registers (http://clinicaltrials.gov/ www.controlled-trials.com www.pactr.org).

This guideline revision is in accordance with procedures outlined by the WHO Guidelines Review Committee and is based on the GRADE approach to evidence review. The process involved four separate working groups: the Internal WHO ART Guideline Working Group, the ART Guideline Drafting Group, the external ART Peer Review Panel and the full ART Guideline Review Committee. The composition of the groups was in accordance with WHO procedures for guideline development and included HIV experts, civil society representatives, programme managers, costing experts, guideline methodologists, epidemiologists, health economists, PEPFAR technical working group representatives, PLHIV community representatives, and WHO regional and country officers. Declarations of Interests were submitted by group participants.

The work was coordinated by the Antiretroviral, Treatment and HIV Care team of the WHO Department of HIV/AIDS.

The academic institutions that contributed to writing the guidelines were the Liverpool Medical School (UK), the South African Medical Research Council / South African Cochrane Centre (South Africa), the University of California, San Francisco / Cochrane Collaborative Review group on HIV/AIDS (USA), the University of New South Wales (Australia) and the University of Bern (Switzerland). Contributions were also received from the US Centers for Disease Control and Prevention (CDC), UNAIDS and the Global Fund to Fight AIDS, Tuberculosis and Malaria. Consultations were held with civil society networks including the Global Network of People Living with HIV (GNP+), the International Treatment Preparedness Coalition (ITCP) and the International Community of Women with HIV/AIDS (ICW).

Group processes were managed as follows. The proposed recommendations were considered separately by the ART Guideline Working and Drafting Groups using a risk-benefit analysis tool consisting of a table exploring the following domains: existing and proposed recommendations, evidence for the outcomes deemed critical (mortality, disease progression and serious adverse events), risks and benefits of implementing the recommendations, acceptability, costs, feasibility, suggested ranking of recommendations (strong or conditional), gaps and research needs. The groups placed emphasis on concerns and important outcomes as voiced by PLHIV and on the critical need to maintain equity, access and coverage.

The draft recommendations, GRADE profiles, risk-benefit analysis tables and supporting data were circulated to the ART Peer Review Panel for comment before convening the multidisciplinary ART Guideline Review Committee in October 2009. Following the release of Rapid advice in November 2009, successive drafts of the full guidelines were prepared and circulated to the ART Guideline Drafting Group and the external ART Peer Review Panel for comments. All responses were considered and addressed in the final draft. Disagreements were resolved in discussions.

The guidelines will be disseminated as a paper-based handbook and electronically on the WHO web site.

Regional and subregional meetings are planned to adapt these global recommendations to local needs and facilitate implementation.

A plan will be developed to evaluate the implementation of the guidelines by users.

A review of the guidelines is planned for 2012. There will be interim reviews as new evidence becomes available.