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Antimicrobial Agents and Chemotherapy, November 2009, p. 4686-4693, Vol. 53, No. 11
0066-4804/09/$08.00+0     doi:10.1128/AAC.00229-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Comparison of Human Immunodeficiency Virus Type 1 Tropism Profiles in Clinical Samples by the Trofile and MT-2 Assays{triangledown}

Eoin Coakley,1 Jacqueline D. Reeves,1 Wei Huang,1 Marga Mangas-Ruiz,2 Irma Maurer,2 Agnes M. Harskamp,2 Soumi Gupta,1 Yolanda Lie,1 Christos J. Petropoulos,1 Hanneke Schuitemaker,2 and Angélique B. van 't Wout2*

Monogram Biosciences, Clinical Research, South San Francisco, California,1 Department of Experimental Immunology, Sanquin Research, Landsteiner Laboratory, and Center for Infectious Diseases and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands2

Received 18 February 2009/ Returned for modification 9 April 2009/ Accepted 7 August 2009

The recent availability of CCR5 antagonists as anti-human immunodeficiency virus (anti-HIV) therapeutics has highlighted the need to accurately identify CXCR4-using variants in patient samples when use of this new drug class is considered. The Trofile assay (Monogram Biosciences) has become the method that is the most widely used to define tropism in the clinic prior to the use of a CCR5 antagonist. By comparison, the MT-2 assay has been used since early in the HIV epidemic to define tropism in clinical specimens. Given that there are few data from direct comparisons of these two assays, we evaluated the performance of the plasma-based Trofile assay and the peripheral blood mononuclear cell (PBMC)-based MT-2 assay for the detection of CXCR4 use in defining the tropism of HIV isolates derived from clinical samples. The various samples used for this comparison were derived from participants of the Amsterdam Cohort Studies on HIV infection and AIDS who underwent consecutive MT-2 assay testing of their PBMCs at approximately 3-month intervals. This unique sample set was specifically selected because consecutive MT-2 assays had demonstrated a shift from negative to positive in PBMCs, reflecting the first emergence of CXCR4-using virus in PBMCs above the level of detection of the assay in these individuals. Trofile testing was performed with clonal HIV type 1 (HIV-1) variants (n = 21), MT-2 cell culture-derived cells (n = 20) and supernatants (n = 42), and plasma samples (n = 76). Among the clonal HIV-1 variants and MT-2 cell culture-derived samples, the results of the Trofile and MT-2 assays demonstrated a high degree of concordance (95% to 98%). Among consecutive plasma samples, detection of CXCR4-using virus was at or before the time of first detection by the MT-2 assay in 5/10 patients by the original Trofile assay and in 9/10 patients by the enhanced-sensitivity Trofile assay. Differences in the time to the first detection of CXCR4 use between the MT-2 assay (PBMCs) and the original Trofile assay (plasma) were greatly reduced by the enhanced-sensitivity Trofile assay, suggesting that sensitivity for the detection of minor CXCR4-using variants may be a more important determinant of discordant findings than compartmentalization. The similarities in performance of the enhanced-sensitivity Trofile and MT-2 assays suggest that either may be an appropriate methodology to define tropism in patient specimens.

* Corresponding author. Mailing address: Laboratory for Viral Immune Pathogenesis, Department of Experimental Immunology, M01-109, Academic Medical Center, University of Amsterdam, Meibergdreef 15, Amsterdam 1105 AZ, The Netherlands. Phone: 31 20 5668251. Fax: 31 20 5669756. E-mail: a.b.vantwout{at}amc.uva.nl

{triangledown} Published ahead of print on 17 August 2009.

Antimicrobial Agents and Chemotherapy, November 2009, p. 4686-4693, Vol. 53, No. 11
0066-4804/09/$08.00+0     doi:10.1128/AAC.00229-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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