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J Acquir Immune Defic Syndr. 2020 Jan 3. doi: 10.1097/QAI.0000000000002281. [Epub ahead of print]

A classifier to predict viral control after antiretroviral treatment interruption in chronic HIV-1 infected patients.

Author information

1
Institute for Research in Biomedicine (IRB Barcelona), the Barcelona Institute for Science and Technology, Barcelona, Catalonia, Spain.
2
Infectious Diseases Department, Hospital Clinic of Barcelona - HIVACAT, University of Barcelona, Barcelona, Spain.
3
Retrovirology and Viral Immunopathology Laboratory, AIDS Research Group, August Pi i Sunyer Biomedical Research Institute (IDIBAPS) - HIVACAT, University of Barcelona, Barcelona, Spain.
4
Honorary Professor of Medicine, University of Barcelona, Senior Global Medical Director, ViiV Healthcare Barcelona, Barcelona, Spain.
5
Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Catalonia, Spain.

Abstract

OBJECTIVES:

To construct a classifier that predicts the probability of viral control after analytical antiretroviral treatment interruptions (ATI) in HIV research trials.

METHODS:

Participants of a dendritic cell-based therapeutic vaccine trial (DCV2) constituted the derivation cohort. One of the primary end-points of DCV2 was the drop of viral load (VL) set point after 12 weeks of ATI (delta VL12). We classified cases as "controllers" (delta VL12 >1 log10 copies/mL, n=12) or"non-controllers" (delta VL12 < 0.5 log10 copies/mL, n= 10), and compared 190 variables (clinical data, lymphocyte subsets, inflammatory markers, viral reservoir, ELISPOT, and lymphoproliferative responses) between the two groups. Naïve Bayes classifiers were built from combinations of significant variables. The best model was subsequently validated on an independent cohort.

RESULTS:

Controllers had significantly higher pre-ART VL (110250 [IQR 71968- 275750] vs. 28600 [IQR 18737-39365] copies/mL, p=0.003) and significantly lower proportion of some T lymphocyte subsets than non-controllers: pre-vaccination CD4+CD45RA+RO+ (1.72% vs. 7.47%, p=0.036), CD8+CD45RA+RO+ (7.92% vs. 15.69%, p=0.017), CD4+CCR5+ (4.25% vs. 7.40%, p=0.011), and CD8+CCR5+ (14.53% vs. 27.30%, p=0.043), and post-vaccination CD4+CXCR4+ (12.44% vs. 22.80%, p=0.021). The classifier based on pre-ART VL and pre-vaccine CD8+CD45RA+RO+ T cells was the best predictive model (overall accuracy: 91%). In an independent validation cohort of 107 ATI episodes, the model correctly identified non-responders (negative predictive value=94%), while it failed to identify responders (positive predictive value=20%).

CONCLUSIONS:

Our simple classifier could correctly classify those patients with low probability of control of VL after ATI. These data could be helpful for HIV research trial design.

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