Definition of Immunological Nonresponse to Antiretroviral Therapy: A Systematic Review

BACKGROUND: Terms and criteria to classify people living with HIV on antiretroviral therapy who fail to achieve satisfactory CD4 T-cell counts are heterogeneous, and need revision and summarization. METHODS: We performed a systematic review of PubMed original research articles containing a set of predefined terms, published in English between January 2009 and September 2018. The search retrieved initially 1360 studies, of which 103 were eligible. The representative terminology and criteria were extracted and analyzed. RESULTS: Twenty-two terms and 73 criteria to define the condition were identified. The most frequent term was "immunological nonresponders" and the most frequent criterion was "CD4 T-cell count <350 cells/µL after ≥24 months of virologic suppression." Most criteria use CD4 T-cell counts as a surrogate, either as an absolute value before antiretroviral therapy initiation or as a change after a defined period of time. Distinct values and time points were used. Only 9 of the 73 criteria were used by more than one independent research team. Herein we propose 2 criteria that could help to reach a consensus. CONCLUSIONS: The high disparity in terms and criteria here reported precludes data aggregation and progression of the knowledge on this condition, because it renders impossible to compare data from different studies. This review will foster the discussion of terms and criteria to achieve a consensual definition.