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Journal of Clinical Microbiology, June 2002, p. 2089-2094, Vol. 40, No. 6
0095-1137/02/$04.00+0     DOI: 10.1128/JCM.40.6.2089-2094.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Detection of Replication-Competent Human Immunodeficiency Virus Type 1 (HIV-1) in Cultures from Patients with Levels of HIV-1 RNA in Plasma Suppressed to Less Than 500 or 50 Copies Per Milliliter

Lisa M. Demeter,^1* Ronald J. Bosch,² Robert W. Coombs,³ Susan Fiscus,⁴ James Bremer,⁵ Victoria A. Johnson,⁶ Alejo Erice,⁷ J. Brooks Jackson,⁸ Stephen A. Spector,⁹ Kathleen M. Squires,^6, Margaret A. Fischl,¹⁰ Michael D. Hughes,² and Scott M. Hammer¹¹

University of Rochester School of Medicine and Dentistry, Rochester,¹ Columbia University, New York,¹¹ New York; Harvard School of Public Health, Boston, Massachusetts,² University of Washington, Seattle, Washington,³ University of North Carolina, Chapel Hill, North Carolina,⁴ Rush Medical College, Chicago, Illinois,⁵ University of Alabama at Birmingham School of Medicine and Birmingham Veterans Affairs Medical Center, Birmingham, Alabama,⁶ University of Minnesota, Minneapolis, Minnesota,⁷ Johns Hopkins University, Baltimore, Maryland,⁸ University of California at San Diego, San Diego, California,⁹ University of Miami School of Medicine, Miami, Florida,¹⁰

Received 17 August 2001/ Returned for modification 29 November 2001/ Accepted 12 March 2002

We determined the frequency with which human immunodeficiency virus (HIV) peripheral blood mononuclear cell cultures convert from positive to negative in subjects enrolled in a substudy of AIDS Clinical Trials Group (ACTG) 320, which compared the efficacy of treatment with a combination of indinavir, zidovudine, and lamivudine (indinavir arm) to that of a combination of zidovudine and lamivudine (dual-nucleoside arm). All subjects included for study had positive baseline HIV cultures. Cultures were performed in real time with 10⁷ fresh patient peripheral blood mononuclear cells, using the ACTG consensus method. We found lower rates of positive HIV cultures in the indinavir treatment arm than in the dual-nucleoside treatment arm (64 versus 96% at week 24, P < 0.001). Within the indinavir arm of the study, we found that positive cultures were less likely to occur in samples with a plasma HIV type 1 (HIV-1) RNA level of <500 copies/ml than in those with a level of 500 copies/ml (44 versus 90%, P < 0.001). In addition, HIV cultures from samples with HIV-1 RNA levels of 500 copies/ml turned positive 8.5 days earlier, on average, than those from samples with levels of <500 copies/ml (P < 0.001). However, 38% of samples with plasma RNA levels of <50 copies/ml still were positive for HIV by culture. Thus, the rates of HIV isolation by standard culture procedures decrease as the plasma viral load decreases below 1,000 copies/ml; however, HIV isolates were still obtained from a substantial proportion of subjects with RNA levels of <50 copies/ml. The delay in the time required for HIV cultures to turn positive should be considered when attempting to obtain an HIV isolate from patients with suppression of plasma viral load.

AIDS Clinical Trials Group Protocol 867.

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