Immunodeficiency at the start of combination antiretroviral therapy: steady improvement or step changes?

Abstract

To the Editors: The IeDEA and ART-CC Collaborations1 recently described CD4 cell counts at the start of combination antiretroviral therapy (cART) in low-, middle-, and high-income countries. The findings accurately highlight the global problem of HIV-positive individuals initiating cART at CD4 cell counts below those recommended currently in the treatment guidelines in 2002–2010. We believe, however, that the analysis could have benefited from 2 main additions. First, the authors modeled CD4 at cART initiation linearly. This methodology does not allow for the expected nonlinear changes to CD4 at cART initiation as guidelines changed throughout the years of analysis. One would expect to see an increase in CD4 at cART initiation in 2006 and 2009 after changes to WHO guidelines recommending earlier antiretroviral therapy initiation.2 Modeling techniques, such as restricted cubic splines,3 would allow the CD4 at cART initiation to move freely by the year of cART initiation. Second, as the authors point out in the discussion, one possible reason for lower median CD4 at cART initiation may be late presentation to HIV care.4 The aim of this work is to aid delivery of public health strategies and interventions, so it is important to know if messages should be geared to more frequent testing or earlier treatment initiation. It would, therefore, be useful if the analysis could be stratified by those who started cART shortly after the first presentation to HIV care (eg, at the next visit after the first available CD4) compared with those under long-term follow-up. Finally, it should be considered that median CD4 at initiation in this analysis is likely to overestimate the true median at initiation, as those who do not initiate are not included in this analysis.