CD4+ T Cell Kinetics and Activation in Human Immunodeficiency Virus—Infected Patients Who Remain Viremic Despite Long-Term Treatment with Protease Inhibitor—Based Therapy

• Published in: The Journal of infectious diseases 2002-02, Vol.185 (3), p.315-323
• Main Authors: Deeks, Steven G., Hoh, Rebecca, Grant, Robert M., Wrin, Terri, Barbour, Jason D., Narvaez, Amy, Cesar, Denise, Abe, Ken, Hanley, Mary Beth, Hellmann, Nicholas S., Petropoulos, Christos J., McCune, Joseph M., Hellerstein, Marc K.
• Format: Article
• Language: English
• Subjects: Adult; Biological and medical sciences; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - physiology; CD8-Positive T-Lymphocytes - immunology; Cell Cycle; Cross-Sectional Studies; Drug Resistance, Viral; HIV Infections - drug therapy; HIV Infections - immunology; HIV Infections - virology; HIV Protease Inhibitors - therapeutic use; Human viral diseases; Humans; Immunophenotyping; Infectious diseases; Lymphocyte Activation; Medical sciences; RNA, Viral - blood; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Viremia - immunology
• ISSN: 0022-1899; 1573-6613; 1537-6613
• DOI: 10.1086/338467

T cell dynamics were studied in human immunodeficiency virus-infected patients who continued using antiretroviral therapy despite detectable plasma viremia (RNA copies > 2500 /mL). CD4+ cell fractional replacement rates, measured by the deuterated glucose technique, were lower in treated patients with detectable viremia than in untreated patients and were similar to those in patients with undetectable viremia. Cell cycle and activation markers exhibited similar trends. For any level of viremia, CD4+ cell fractional replacement rates were lower in patients with drug-resistant virus than in patients with wild-type virus, which suggests that the resistant variant was less virulent. Interruption of treatment in patients with drug-resistant viremia resulted in increased CD4+ cell activation, increased CD4+ cell turnover, and decreased CD4+ cell counts. These data indicate that partial virus suppression reduces CD4+ cell turnover and activation, thereby resulting in sustained CD4+ cell gains, and that measurements of T cell dynamics may provide an in vivo marker of viral virulence.