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Journal of Clinical Microbiology, June 2007, p. 1783-1788, Vol. 45, No. 6
0095-1137/07/$08.00+0     doi:10.1128/JCM.00056-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Both Human Immunodeficiency Virus Cellular DNA Sequencing and Plasma RNA Sequencing Are Useful for Detection of Drug Resistance Mutations in Blood Samples from Antiretroviral-Drug-Naive Patients{triangledown}

Saverio G. Parisi,1* Caterina Boldrin,1 Mario Cruciani,2 Giangiacomo Nicolini,3 Isabella Cerbaro,1 Vinicio Manfrin,4 Federico Dal Bello,1 Elisa Franchin,1 Marzia Franzetti,5 Maria C. Rossi,6 Anna M. Cattelan,5 Laura Romano,7 Maurizio Zazzi,7 Massimo Andreoni,8 and Giorgio Palù1

Department of Histology, Microbiology and Medical Biotechnology, Padova University, Padova,1 Center of Preventive Medicine and HIV Outpatient Clinic, Verona,2 Infectious Diseases Unit, Schio Hospital, Schio,3 Infectious Diseases Unit, Vicenza Hospital, Vicenza,4 Infectious Diseases Unit, Padova Hospital, Padova,5 Infectious Diseases Unit, Treviso Hospital, Treviso,6 Department of Molecular Biology, University of Siena, Siena,7 Department of Public Health, University of Roma Tor Vergata, Rome, Italy8

Received 8 January 2007/ Returned for modification 25 March 2007/ Accepted 7 April 2007

Genotypic antiretroviral testing is recommended for newly infected drug-naive subjects, and the material of choice is plasma RNA. Since drug resistance mutations (DRMs) may persist longer in cellular DNA than in plasma RNA, we investigated whether the use of peripheral blood mononuclear cell (PBMC) human immunodeficiency virus (HIV) DNA increases the sensitivity of genotypic testing in antiretroviral-drug-naive subjects. We compared the rate of primary drug resistance in plasma RNA and PBMC DNA in 288 HIV type 1-infected drug-naive persons tested at a single clinical virology center from June 2004 to October 2006. Resistance in the plasma compartment to at least one drug was detected for 64 out of 288 (22.2%) naive patients and in the PBMC compartment for 56 (19.4%) patients. Overall, DRMs were found in 80 out of 288 (27.8%) patients. PBMC DRMs were present in plasma RNA from 16 subjects with wild-type virus infections. Another nine patients had additional DRMs in PBMCs with respect to those detected in plasma RNA. On the other hand, extra plasma DRMs were detected in PBMCs for 24 and 8 subjects with wild-type and drug-resistant virus, respectively. Resistance to more than one class of antiretroviral drug was detected by plasma and PBMC analysis for 25.0% and 36.2% of the subjects, respectively. Our data support the potential utility of genotypic resistance testing of PBMC DNA in conjunction with the currently recommended plasma RNA analysis.


* Corresponding author. Mailing address: Department of Histology, Microbiology and Medical Biotechnology, Padova University, via Gabelli 63, 35100 Padova, Italy. Phone: 39-049-8272344. Fax: 39-049-8272355. E-mail: saverio.parisi{at}unipd.it

{triangledown} Published ahead of print on 18 April 2007.


Journal of Clinical Microbiology, June 2007, p. 1783-1788, Vol. 45, No. 6
0095-1137/07/$08.00+0     doi:10.1128/JCM.00056-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.