during primary HIV-1 infection and impact on disease progression.

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

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). The authors determined HIV-1 tropism in both these compartments during primary infection and evaluated the impact of CXCR4-using viruses on disease progression. 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. HIV-1 coreceptor usage was determined using a recombinant virus phenotypic entry assay and V3-based genotypic algorithms. They also monitored CD4 T-cell count, clinical events and therapeutic intervention. 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/μl and by a reduced delay in initiating a first antiretroviral treatment. 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.

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Editors’ note: When HIV gp120 binds to the CD4 cell, a chemokine receptor site on the cell becomes exposed for the virus to dock. CCR5 viruses, called R5-tropic viruses, then use the CCR5 chemokine receptor on the cell surface to get entry into the cell while CXCR4 viruses, called X4-tropic viruses, use the CXCR4 receptor. Yet other viruses are dual tropic, using either receptor. Which coreceptor HIV has a predilection for can influence clinical evolution. Fortunately, most people appear to have predominantly CCR5 virus until late in infection when CXCR4 viruses emerge and are associated with accelerated declines in CD4 counts and progression to AIDS. What causes this transition is not clear. This study found that people who inject drugs were more likely to have a dual tropic virus R5X4 in primary infection that was associated with a faster disease progression, measured as time to CD4 count 350 cells/mm³ or initiation of first antiretroviral treatment. This may be because R4 CD4 cells are more abundant in blood than in genital and rectal mucosa. This is an area for further exploration in larger studies – CCR5 antagonists have been developed but we have no drugs to block HIV binding to CXCR4 receptors.