This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nicastri, E. Articles by Andreoni, M. Search for Related Content PubMed PubMed Citation Articles by Nicastri, E. Articles by Andreoni, M.

 Previous Article  |  Next Article 

Journal of Clinical Microbiology, July 2003, p. 3007-3012, Vol. 41, No. 7
0095-1137/03/$08.00+0     DOI: 10.1128/JCM.41.7.3007-3012.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

High Prevalence of M184 Mutation among Patients with Viroimmunologic Discordant Responses to Highly Active Antiretroviral Therapy and Outcomes after Change of Therapy Guided by Genotypic Analysis

Department of Public Health, University of Rome Tor Vergata,² National Institute of Infectious Diseases, IRCCS L. Spallanzani,¹ Department of Infectious Diseases University of Rome La Sapienza,³ Laboratory of Virology, Istituto Superiore di Sanità, Rome,⁵ Institute of Immunology and Infectious Diseases, University of Verona, Verona, Italy⁴

Received 13 November 2002/ Returned for modification 18 March 2003/ Accepted 24 April 2003

Whether highly active antiretroviral therapy (HAART) should be modified in patients with persistent increases in CD4⁺ T cells despite detectable viral loads is an unresolved question. Forty-three heavily pretreated human immunodeficiency virus (HIV)-infected patients with virologic failure during HAART were studied before a change of therapy guided by genotypic analysis and during follow-up. Patients with an increase in CD4⁺ cell count (>100 cells/ml) over pre-HAART values were considered to be discordant patients (20 individuals), whereas patients with a lower increase or no increase in CD4⁺ cell count were considered failing patients (23 individuals). Based on univariate analysis, a high CD4⁺ cell count before antiretroviral treatment, homosexual behavior as a risk factor for HIV infection, reduced drug exposure to nonnucleoside reverse transcriptase inhibitors, low replicative capacity of HIV isolates, and more frequent detection of HIV isolates with a non-B subtype, an R5 biological phenotype, and M184V and T215Y/F mutations were factors associated with a discordant response to HAART. Based on multivariate analysis, only the M184V mutation remained significantly associated with a viroimmunologic discordant response (odds ratio, 25.48; 95% confidence interval, 1.43 to 453.93). No difference in lamivudine exposure was found between discordant (95%) and failing (91%) patients. Twelve months after the genotypic analysis-guided change of therapy, 3 discordant (15%) and 6 failing patients (26%) achieved undetectable viral loads (<50 copies/ml), whereas in patients with HIV RNA loads of >500 copies/ml, discordant responses were observed in 5 out of 15 discordant patients and in 4 out of 16 failing patients. A relationship between the M184V mutation and a viroimmunologic discordant response to HAART was found. After the genotypic analysis-driven change of therapy, similar rates of virologic suppression were detected in the two groups.

This article has been cited by other articles:

• Schechter, M., Tuboi, S. H. (2006). Discordant immunological and virological responses to antiretroviral therapy. J Antimicrob Chemother 58: 506-510 [Abstract] [Full Text]  
• Petrella, M., Oliveira, M., Moisi, D., Detorio, M., Brenner, B. G., Wainberg, M. A. (2004). Differential Maintenance of the M184V Substitution in the Reverse Transcriptase of Human Immunodeficiency Virus Type 1 by Various Nucleoside Antiretroviral Agents in Tissue Culture. Antimicrob. Agents Chemother. 48: 4189-4194 [Abstract] [Full Text]  
• Maranon, C., Desoutter, J.-F., Hoeffel, G., Cohen, W., Hanau, D., Hosmalin, A. (2004). Dendritic cells cross-present HIV antigens from live as well as apoptotic infected CD4+ T lymphocytes. Proc. Natl. Acad. Sci. USA 101: 6092-6097 [Abstract] [Full Text]