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Journal of Virology, January 2002, p. 707-716, Vol. 76, No. 2
0022-538X/01/$04.00+0     DOI: 10.1128/JVI.76.2.707-716.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Evidence for Human Immunodeficiency Virus Type 1 Replication In Vivo in CD14⁺ Monocytes and Its Potential Role as a Source of Virus in Patients on Highly Active Antiretroviral Therapy

Departments of Laboratory Medicine,¹ Microbiology, University of Washington School of Medicine, Seattle, Washington 98195,² Programs in Biostatistics,³ Infectious Diseases, Fred Hutchinson Cancer Research Center, Seattle, Washington 98104⁴

Received 23 May 2001/ Accepted 28 September 2001

In vitro studies show that human immunodeficiency virus type 1 (HIV-1) does not replicate in freshly isolated monocytes unless monocytes differentiate to monocyte-derived macrophages. Similarly, HIV-1 may replicate in macrophages in vivo, whereas it is unclear whether blood monocytes are permissive to productive infection with HIV-1. We investigated HIV-1 replication in CD14⁺ monocytes and resting and activated CD4⁺ T cells by measuring the levels of cell-associated viral DNA and mRNA and the genetic evolution of HIV-1 in seven acutely infected patients whose plasma viremia had been <100 copies/ml for 803 to 1,544 days during highly active antiretroviral therapy (HAART). HIV-1 DNA was detected in CD14⁺ monocytes as well as in activated and resting CD4⁺ T cells throughout the course of study. While significant variation in the decay slopes of HIV-1 DNA was seen among individual patients, viral decay in CD14⁺ monocytes was on average slower than that in activated and resting CD4⁺ T cells. Measurements of HIV-1 sequence evolution and the concentrations of unspliced and multiply spliced mRNA provided evidence of ongoing HIV-1 replication, more pronounced in CD14⁺ monocytes than in resting CD4⁺ T cells. Phylogenetic analyses of HIV-1 sequences indicated that after prolonged HAART, viral populations related or identical to those found only in CD14⁺ monocytes were seen in plasma from three of the seven patients. In the other four patients, HIV-1 sequences in plasma and the three cell populations were identical. CD14⁺ monocytes appear to be one of the potential in vivo sources of HIV-1 in patients receiving HAART.

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