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

• Published in: Journal of Clinical Microbiology 2007-06, Vol.45 (6), p.1783-1788
• Main Authors: Parisi, Saverio G, Boldrin, Caterina, Cruciani, Mario, Nicolini, Giangiacomo, Cerbaro, Isabella, Manfrin, Vinicio, Dal Bello, Federico, Franchin, Elisa, Franzetti, Marzia, Rossi, Maria C, Cattelan, Anna M, Romano, Laura, Zazzi, Maurizio, Andreoni, Massimo, Palù, Giorgio
• Format: Article
• Language: English
• Subjects: Adult; Anti-HIV Agents - pharmacology; Anti-HIV Agents - therapeutic use; Biological and medical sciences; DNA, Viral - analysis; Drug Resistance, Viral - genetics; Female; Fundamental and applied biological sciences. Psychology; HIV Infections - drug therapy; HIV Infections - virology; HIV-1 - classification; HIV-1 - drug effects; HIV-1 - genetics; Human immunodeficiency virus; Humans; Infectious diseases; Leukocytes, Mononuclear - virology; Male; Medical sciences; Microbial Sensitivity Tests - methods; Microbiology; Middle Aged; Miscellaneous; Mutation; RNA, Viral - analysis; RNA, Viral - blood; Sequence Analysis, DNA; Virology
• ISSN: 0095-1137; 1098-660X; 1098-5530
• DOI: 10.1128/JCM.00056-07

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.