Keith Henry, MD reviewing Kelly C et al. PLoS One 2016 Jun 10.

A review of the literature concludes that discordant immune recovery on antiretroviral therapy is associated with a marked increase in mortality in most studies.

A discordant immune response (DIR) is loosely defined as a failure to observe a satisfactory increase in CD4-cell counts on antiretroviral therapy (ART) despite good viral suppression. The authors systematically evaluated studies that assessing the effect of DIR on mortality, AIDS, and serious non-AIDS events. They included cohort studies and cohorts contained in arms of randomized controlled trials, for adults aged ≥16 years. They used the Cochrane tool to measure bias. For this analysis, DIR was classified as suboptimal CD4-cell count, as defined by each study, despite viral suppression after at least 6 months of ART.

Of 2782 study titles, 20 studies met the inclusion criteria. The included studies used a total of 14 definitions of DIR. The overall risk for mortality ranged between 3% and 23% for patients with DIR versus between 1% and 7% for patients without DIR, during a median follow-up of 2.0 to 3.7 years. Risk ratios for mortality in patients with versus without DIR varied from 1.00 to 4.29; most studies reported a two- to threefold increase in mortality. The authors propose standardizing the definition of DIR as failure to achieve at least a 50 cell/mm3 increase in CD4-cell count 6 months after starting ART in patients with CD4 count <350 cells/mm3 at ART initiation.

CITATION(S):

Kelly C et al. Discordant immune response with antiretroviral therapy in HIV-1: A systematic review of clinical outcomes. PLoS One 2016 Jun 10; 11:e0156099. 

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