Consolidated ARV guidelines 2013

When to start ART in adults and adolescents: Rationale and supporting evidence

Populations for which no specific new recommendation is made

The Guidelines Development Group did not find evidence and/or favourable risk–benefit profiles to support recommendations for initiating ART at CD4 cell count >500 cells/mm3 or regardless of CD4 cell count or WHO clinical stage in the following populations.

Individuals with HIV who are 50 years of age and older

A pooled analysis of data from 13 cohorts from Europe and North America showed increased risk of death and disease progression in people with HIV older than 50 years of age (26). However, these data were not stratified by CD4 cell count and do not support initiating ART at CD4 counts > 500 cells/mm3 for this group.

Individuals with HIV-2

The lack of randomized treatment studies in individuals with HIV-2 makes it difficult to determine the optimal timing of ART initiation in this population. A systematic review (Web Annex) evaluated observational data from 15 studies and showed no significant differences between initiating ART at a CD4 count ≤350 cells/mm3 and >350 cells/mm3, considering the outcomes of mortality, disease progression, increase in CD4 cell count, virological response and risk of drug resistance. The quality of evidence was rated as low to very low, with serious risk of bias and imprecision (few events) for all these outcomes.

Individuals coinfected with HIV and HCV

Observational studies have shown that coinfection with HIV and HCV accelerates HCVrelated progression of liver fibrosis and leads to a higher rate of end-stage liver disease (63) and mortality (63–65).

There is consistent but low-quality observational data about the overall benefit of ART on mortality and progression of liver disease in individuals coinfected with HIV and HCV based on evidence from a meta-analysis (66) , and a review of nine cohort studies that examined the relationship between ART and hepatic fibrosis showing that ART was associated with a decreased rate of liver fibrosis progression, although this was not evaluated by the level of CD4 count (Web Annex). The Guidelines Development Group endorsed the special note in the 2010 guidelines (2) that initiating ART among people coinfected with HCV should follow the same principles as in HIV monoinfection. Initiating ART regardless of CD4 cell count was not recommended because of lack of evidence.

There are challenges in diagnosing and treating active HCV infection in settings with limited access to HCV antibody and RNA assays, diagnostic tools for staging of liver disease (such as biopsy) and HCV therapy and in certain populations such as people who inject drugs. However, limited access to HCV testing or treatment and/or high rates of HCV infection should not be barriers to initiating ART.

WHO hepatitis guidelines forthcoming in 2014 will provide detailed guidance on HCV screening, treatment and care. People coinfected with HIV and HCV receiving ART and HCV drugs require close monitoring because of potential drug interactions and increased risk for drug toxicity between HCV drugs (such as interferon, ribavirin and newer directly acting agents) and ARV drugs.

Key populations

The scale-up of ARV drugs for preventing HIV infection or reducing HIV incidence in key populations has been evaluated in community-wide and ecological studies and mathematical models (67–79). Some of these studies showed a reduction in the community viral load, with and without an associated decline in HIV incidence, invariably where ART coverage is high or access to ART is expanding rapidly. However, the Guidelines Development Group concluded that there is insufficient evidence to recommend earlier initiation of ART in key populations regardless of CD4 cell count. The initiation of ART in key populations should follow the same general principles and recommendations as in other adults and adolescents with HIV.