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Journal of Virology, November 2003, p. 12105-12112, Vol. 77, No. 22
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.22.12105-12112.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Relationship between In Vitro Human Immunodeficiency Virus Type 1 Replication Rate and Virus Load in Plasma

Thomas B. Campbell,1 Kristina Schneider,1,{dagger} Terri Wrin,2 Christos J. Petropoulos,2 and Elizabeth Connick1*

Division of Infectious Diseases, University of Colorado Health Sciences Center, Denver, Colorado 80262,1 ViroLogic, Inc., South San Francisco, California 940802

Received 19 May 2003/ Accepted 13 August 2003

Although plasma human immunodeficiency virus type 1 (HIV-1) RNA concentration is a major determinant of the rate of HIV-1 disease progression, the reasons for variability in plasma virus loads among infected individuals are not fully understood. We conducted investigations with 15 HIV-1-infected individuals who were not receiving antiretroviral therapy to evaluate the hypothesis that HIV-1 replication rate in vitro is a significant determinant of plasma virus load. Virus could not be isolated from one subject. Two subjects were excluded because they had features previously associated with distinct plasma virus loads and altered rates of disease progression; one harbored a syncytium-inducing virus and the second was heterozygous for a 32-bp deletion from the CCR5 gene. HIV-1 replication rates were determined by culturing autologous virus isolates in phytohemagglutinin-treated peripheral blood mononuclear cells (PBMC) and determining the rate of p24 antigen production during the logarithmic phase of viral replication. The contribution of HIV-1 reverse transcriptase (RT) and protease (PR) alleles to replication capacity was assessed using recombinant viruses in a single-cycle infection assay. HIV-1 replication rates ranged from 0.15 to 0.76 log10 pg/ml/day and were reproducible within the same donor PBMC (coefficient of variation ± 4%). RT-PR replication capacity ranged from 14 to 95% of that of control virus and was linearly related to replication rate (r2 = 0.53; P = 0.007). Plasma HIV-1 RNA concentration was linearly related to replication rate (r2 = 0.71; P < 0.001) and RT-PR replication capacity (r2 = 0.44; P = 0.019). These data suggest that different RT-PR alleles are important determinants of HIV-1 replication rates and that HIV-1 replication rate explains much of the variability in plasma virus load in chronic HIV-1 infection.

* Corresponding author. Mailing address: Division of Infectious Diseases, University of Colorado Health Sciences Center, Box B168, 4200 E. Ninth Ave., Denver, CO 80262. Phone: (303) 315-0906. Fax: (303) 315-8681. E-mail: liz.connick{at}uchsc.edu.

{dagger} Present address: Children's Hospital, Denver, CO 80218.

Journal of Virology, November 2003, p. 12105-12112, Vol. 77, No. 22
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.22.12105-12112.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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