Preliminary Data From the Study of Coagulative Profile of HIV Infected Individuals Suggest a Role For Point Mutations in the Gene in Protein S Deficiency in Individuals Undergoing Highly Antiretroviral Therapy

Mariantonietta Di Stefano1, 2, #, Giovanna D’Andrea2, #, Fabio Zoboli1, Giuseppina Faleo1, Massimo Fasano1, Domenico Martinelli3, Maurizio Margaglione2, Teresa A. Santantonio1, Josè R. Fiore1, *
1 Department of Clinical and Experimental Medicine, Section of Infectious Diseases, University of Foggia, Viale L. Pinto 71131Foggia, Italy
2 Medical Genetics, University of Foggia, Viale L. Pinto 71131Foggia, Italy
3 Department of Medical Sciences, Section of Hygiene, University of Foggia, Apulia Regional Epidemiological Observatory, Viale L. Pinto 71131Foggia, Italy

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© 2018 Di Stefano et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

# Contributed equally.* Address correspondence to this author at the Department of Clinical and Experimental Medicine, Jose Ramon Fiore MD, PhD, University of Foggia, School of Medicine, 71100 Foggia, Italy; Tel: +393284732048; E-mail:



HIV infection is a known prothrombotic condition but factors involved are still controversial. A role for antiretrovirals, especially protease inhibitors, was advocated.


The study aimed to analyze the levels of anticoagulant proteins in virally suppressed HIV-infected subjects treated with different anti-retroviral regimens.

Materials and Methods:

Forty-four patients were included in the study. C and PS, D-Dimers and Fibrinogen levels were determined as well as APC-resistance. PROS1 gene was sequenced in a group of patient.


Twelve of the 44 subjects (27%) showed reduced levels of PS, while lower levels of PC were found only in 2 patients (4,5%). No difference in the mean values of PC and PS was found stratifying the study population by antiretroviral regimen administrated (p>0.05).

Three patients had higher levels of D-Dimer concentrations and in two of these patients, an association between higher D-Dimer values and lower levels of PS was observed; but however no correlation was found by statistical analysis.

PROS1 gene analysis was performed in 26 of the 44 HIV-1 patients and the subjects with low levels of PS had mutation in the fifteen exon of PROS 1 gene. While among individuals with normal levels, this mutation was observed only in 8/18 (44%) of the cases (p=0,0072).


The majority of patients with low PS levels also had mutations in the fifteen exon of PROS 1 gene. Genetic determinants, deserving further investigations, rather than antiretrovirals might cause PS deficiency in HIV-1 positive patients.

Keywords: Protein S, Protein C, Thrombosis, HIV, Antiretrovirals, Pros 1 gene, PS deficiency.