nonCCR5tropic

NonCCR5tropic is a term used in HIV research and clinical practice to describe HIV-1 strains that do not rely on the CCR5 co-receptor to enter target cells. Most circulating HIV-1 strains are R5-tropic and use CCR5, but nonCCR5tropic strains use other co-receptors, most commonly CXCR4 (X4-tropic) or express dual-tropism, enabling entry via multiple pathways.

In tropism classification, viruses are commonly categorized as R5-tropic (CCR5-using), X4-tropic (CXCR4-using), or dual/mixed-tropism (can use both CCR5 and CXCR4). The nonCCR5tropic designation therefore covers X4-tropic and dual-tropic viruses. This distinction is clinically important because CCR5 antagonists, such as maraviroc, block only CCR5-using viruses and are ineffective against nonCCR5tropic strains.

Tropism testing to identify nonCCR5tropic viruses can be performed with phenotypic assays or genotypic approaches. Phenotypic tests assess actual co-receptor usage in vitro (e.g., through cell entry assays), while genotypic tests infer tropism from the env gene, particularly the V3 loop. Test results can guide treatment decisions, as the presence of nonCCR5tropic virus may prompt selection of antiretroviral regimens that do not rely on CCR5 blockade.

Clinically, R5-tropism is common in early infection, and some patients may acquire X4-tropic or dual-tropic viruses later, which can influence disease progression and treatment options. The nonCCR5tropic status of a viral population can be dynamic and vary by tissue compartment and time.