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

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;...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of clinical investigation 2001-02, Vol.107 (4), p.431-438
Main Authors: Philpott, S, Weiser, B, Anastos, K, Kitchen, C M, Robison, E, Meyer, 3rd, W A, Sacks, H S, Mathur-Wagh, U, Brunner, C, Burger, H
Format: Article
Language:English
Subjects:
Anti-HIV Agents - pharmacology
Antiretroviral Therapy, Highly Active
CD4 antigen
CD4 Lymphocyte Count
CXCR4 protein
Female
HIV-1 - drug effects
HIV-1 - physiology
Human immunodeficiency virus 1
Humans
Receptors, CXCR4 - physiology
RNA, Viral - chemistry
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0021-9738
DOI:10.1172/JCI11526