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Definition of Immunological Nonresponse to Antiretroviral Therapy

A Systematic Review

Rb-Silva, Rita MDa,b,c; Goios, Ana PhDa,b; Kelly, Christine PhDd; Teixeira, Pedro PhDa,b; João, Cristina MD, PhDe,f; Horta, Ana MD, PhDa,b,g; Correia-Neves, Margarida PhDa,b,h

JAIDS Journal of Acquired Immune Deficiency Syndromes: December 15, 2019 - Volume 82 - Issue 5 - p 452–461
doi: 10.1097/QAI.0000000000002157
Clinical Science

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.

aLife and Health Sciences Research Institute, School of Medicine, University of Minho, Braga, Portugal;

bICVS/3B's, PT Government Associate Laboratory, Braga/Guimarães, Portugal;

cDepartment of Onco-Hematology, Portuguese Institute of Oncology of Porto, Porto, Portugal;

dHIV Molecular Research Group, University College Dublin, Dublin, Ireland;

eNOVA Medical School, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisboa, Portugal;

fChampalimaud Centre for the Unknown, Fundação Champalimaud, Lisboa, Portugal;

gDepartment of Infectious Diseases, Centro Hospitalar do Porto, Porto, Portugal; and

hDivision of Infectious Diseases, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.

Correspondence to: Margarida Correia-Neves, PhD, Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal (e-mail:

Supported by: FEDER, through the Competitiveness Factors Operational Program (COMPETE); by National funds, through the Foundation for Science and Technology (FCT), under the scope of the project POCI-01-0145-FEDER-007038 and NORTE-01-0145-FEDER-000013; and by Programa Gilead GÉNESE (PGG/018/2017). R.R.-S. was supported by an FCT grant, in the context of PhDOC—Doctoral Program in Ageing and Chronic Diseases (PD/BD/106047/2015).

A.H. is consultant for Abbvie LDA, Bristol-Myers Squibb, Gilead Sciences, Janssen-Cilag, Merck Sharp and Dohme and ViiV Healthcare. C.J. serves as adviser for Celgene, Janssen-Cilag and Takeda. R.R.-S., A.G., C.K., P.T., and M.C.-N. have nothing to disclose.

R.R.-S. and A.G. conceived and designed the review, performed the search and analyzed the data. M.C.-N. coordinated all the steps of the review. R.R.-S., A.G., C.K., P.T., C.J., A.H., and M.C.-N. contributed to the writing and revision of the manuscript. All authors discussed the results and contributed to the final manuscript.

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Received June 19, 2019

Accepted August 12, 2019

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