CXCR4-using viruses in plasma and peripheral blood mononuclear cells during primary HIV-1 infection and impact on disease progression.

Abstract

OBJECTIVE:

Cysteine-cysteine receptor 5 (CCR5)-using viruses classically predominate during HIV-1 primary infection but the frequency of cysteine-X-cysteine receptor 4 (CXCR4)-using viruses varies between studies and could be different between plasma and peripheral blood mononuclear cells (PBMCs). Thus, we determined HIV-1 tropism in both these compartments during primary infection and evaluated the impact of CXCR4-using viruses on disease progression.

DESIGN:

One hundred and thirty-three patients with primary HIV-1 infection were screened for HIV-1 coreceptor usage in plasma and PBMCs using both genotypic and phenotypic methods. The impact of CXCR4-using viruses' transmission on subsequent disease progression was assessed in a case-control study.

METHODS:

HIV-1 coreceptor usage was determined using a recombinant virus phenotypic entry assay and V3-based genotypic algorithms. We also monitored CD4(+) T-cell count, clinical events and therapeutic intervention.

RESULTS:

There was 6.4% of CXCR4-using HIV-1 in plasma during primary infection as measured by a phenotypic assay and combined criteria from the 11/25 and net charge genotypic rules. Geno2pheno10 overestimated the prevalence of CXCR4-using viruses (12%). HIV-1 tropism in plasma and PBMCs was 98% concordant. The HIV-1 RNA load and CD4(+) T-cell count during primary infection were not related to virus tropism. Primary infection with CXCR4-using viruses was associated with an accelerated rate of disease progression, estimated by a faster decline of CD4 T-cell count under 350 cells/microl and by a reduced delay in initiating a first antiretroviral treatment.

CONCLUSIONS:

Plasma or PBMC samples can be used for determining HIV-1 tropism during primary infection. CXCR4-using viruses are rare during primary infection but increase the risk of disease progression.

• Authors: Stéphanie Raymond, Pierre Delobel, Maud Mavigner, Michelle Cazabat, Stéphanie Encinas, Corinne Souyris, Patrick Bruel, Karine Sandres-Sauné, Bruno Marchou, Patrice Massip, Jacques Izopet
• Journal: AIDS (London, England) (AIDS) Vol. 24 Issue 15 Pg. 2305-12 (Sep 24 2010) ISSN: 1473-5571 [Electronic] England
• PMID: 20808203 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Receptors, CCR5
• Receptors, CXCR4

Topics

• Adult
• CD4 Lymphocyte Count
• Case-Control Studies
• Disease Progression
• Female
• Genotype
• HIV Infections (genetics, immunology)
• HIV-1 (physiology)
• Humans
• Male
• Phenotype
• Receptors, CCR5 (genetics, immunology)
• Receptors, CXCR4 (genetics, immunology)
• Viral Tropism (physiology)