HIV-1 Tropism Test Evaluation: Assessment and Clinical Implications

Abstract

CCR5 and CXCR4 chemokines receptors are critical coreceptors for the binding of HIV to specific host cells. Guidelines recommend its assessment in case of virological failure or before prescription of CCR5 inhibitors. Strategies to assess viral tropism may be divided into phenotypic and genotypic assays; registrative trials of CCR5 inhibitors used phenotypic assay, but recently genotypic ones have been used in clinical practice. The presence of CXCR4 is increasing in naïve patients, with both acute and chronic HIV-1 infections; this coreceptor usage is associated with CD4 depletion. The assessment of viral tropism should be considered in every stage of HIV-1 infection.

Mechanisms of HIV-1 cell-to-cell transfer to myeloid cells

“…The viral envelope also determines the cellular tropism of the HIV‐1 strains that can be classified in 3 types: CXCR4‐using T cell‐tropic, CCR5‐using T cell‐tropic (also called non‐macrophage‐tropic), and macrophage‐tropic strains using either CCR5 or CXCR4, or both, as coreceptors 16 . Although CCR5‐using viruses, including sexually transmitted/founder (T/F) viruses, 17,18 predominate during early, acute, and asymptomatic phases of infection, CXCR4‐using variants can emerge at later stage of infection and are mostly associated with advanced disease progression 19–21 …”

“…16 Although CCR5-using viruses, including sexually transmitted/founder (T/F) viruses, 17,18 predominate during early, acute, and asymptomatic phases of infection, CXCR4using variants can emerge at later stage of infection and are mostly associated with advanced disease progression. [19][20][21] The first block to efficient macrophage infection is related to virus entry and specific cellular tropism of the different HIV-1 variants found in infected individuals and characterized as non-M-tropic using cellfree in vitro infection assays. Poor virus replication in these myeloid cells is also largely related to the high expression and/or efficiency of host cell restriction factors that inhibit postentry replication steps of the viral life cycle, such as SAMHD1 (SAM domain and HD domaincontaining protein 1), an enzyme that inhibits the reverse transcription process through depletion of the pool of intracellular nucleotides necessary for efficient synthesis of the viral DNA, but also members of the APOBEC3 (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3), TRIM (TRIpartite Motif protein), and IFITM (InterFeron-Induced TransMembrane protein) families.…”