Preferential suppression of CXCR4-specific strains of HIV-1 by antiviral therapy

S. Philpott, Barbara Weiser, K. Anastos, C. M. Ramirez Kitchen, E. Robison, W. A. Meyer, H. S. Sacks, U. Mathur-Wagh, C. Brunner, Harold Burger

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

To initiate infection, HIV-1 requires a primary receptor, CD4, and a secondary receptor, principally the chemokine receptor CCR5 or CXCR4. Coreceptor usage plays a critical role in HIV-1 disease progression. HIV-1 transmitted in vivo generally uses CCR5 (R5), but later CXCR4 (X4) strains may emerge; this shift heralds CD4+ cell depletion and clinical deterioration. We asked whether antiretroviral therapy can shift HIV-1 populations back to R5 viruses after X4 strains have emerged, in part because treatment has been successful in slowing disease progression without uniformly suppressing plasma viremia. We analyzed the coreceptor usage of serial primary isolates from 15 women with advanced disease who demonstrated X4 viruses. Coreceptor usage was determined by using a HOS-CD4+ cell system, biological and molecular cloning, and sequencing the envelope gene V3 region. By constructing a mathematical model to measure the proportion of virus in a specimen using each coreceptor, we demonstrated that the predominant viral population shifted from X4 at baseline to R5 strains after treatment. Multivariate analyses showed that the shift was independent of changes in plasma HIV-1 RNA level and CD4+ cell count. Hence, combination therapy may lead to a change in phenotypic character as well as in the quantity of HIV-1. Shifts in coreceptor usage may thereby contribute to the clinical efficacy of anti-HIV drugs.

Original languageEnglish (US)
Pages (from-to)431-438
Number of pages8
JournalJournal of Clinical Investigation
Volume107
Issue number4
StatePublished - 2001
Externally publishedYes

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Antiviral Agents
HIV-1
Viruses
Disease Progression
Therapeutics
Anti-HIV Agents
CD4 Antigens
Chemokine Receptors
Viremia
Molecular Cloning
CD4 Lymphocyte Count
Population
Theoretical Models
Multivariate Analysis
RNA
Infection
Genes

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Philpott, S., Weiser, B., Anastos, K., Ramirez Kitchen, C. M., Robison, E., Meyer, W. A., ... Burger, H. (2001). Preferential suppression of CXCR4-specific strains of HIV-1 by antiviral therapy. Journal of Clinical Investigation, 107(4), 431-438.

Preferential suppression of CXCR4-specific strains of HIV-1 by antiviral therapy. / Philpott, S.; Weiser, Barbara; Anastos, K.; Ramirez Kitchen, C. M.; Robison, E.; Meyer, W. A.; Sacks, H. S.; Mathur-Wagh, U.; Brunner, C.; Burger, Harold.

In: Journal of Clinical Investigation, Vol. 107, No. 4, 2001, p. 431-438.

Research output: Contribution to journalArticle

Philpott, S, Weiser, B, Anastos, K, Ramirez Kitchen, CM, Robison, E, Meyer, WA, Sacks, HS, Mathur-Wagh, U, Brunner, C & Burger, H 2001, 'Preferential suppression of CXCR4-specific strains of HIV-1 by antiviral therapy', Journal of Clinical Investigation, vol. 107, no. 4, pp. 431-438.
Philpott S, Weiser B, Anastos K, Ramirez Kitchen CM, Robison E, Meyer WA et al. Preferential suppression of CXCR4-specific strains of HIV-1 by antiviral therapy. Journal of Clinical Investigation. 2001;107(4):431-438.
Philpott, S. ; Weiser, Barbara ; Anastos, K. ; Ramirez Kitchen, C. M. ; Robison, E. ; Meyer, W. A. ; Sacks, H. S. ; Mathur-Wagh, U. ; Brunner, C. ; Burger, Harold. / Preferential suppression of CXCR4-specific strains of HIV-1 by antiviral therapy. In: Journal of Clinical Investigation. 2001 ; Vol. 107, No. 4. pp. 431-438.
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