What is a tropism test for in Human Immunodeficiency Virus (HIV) treatment?

HIV Tropism Testing: Purpose and Clinical Application

A tropism test is essential before prescribing CCR5 antagonist medications like maraviroc in HIV treatment, as these drugs are only effective against CCR5-tropic HIV variants and ineffective against CXCR4-using or dual/mixed-tropic viral strains. 1

What is Viral Tropism?

Viral tropism refers to the ability of HIV to enter and infect specific host cells based on which coreceptors the virus can bind to:

• CCR5-tropic (R5): HIV variants that use the CCR5 coreceptor to enter cells
• CXCR4-tropic (X4): HIV variants that use the CXCR4 coreceptor
• Dual/mixed-tropic (D/M): HIV variants that can use both coreceptors

Clinical Importance of Tropism Testing

Tropism testing is recommended for the following patient groups:

• Drug-naïve patients in whom toxic effects are anticipated or who have limited treatment options
• Patients with poor tolerability to current treatment or with CNS pathology
• Patients with treatment failure for whom CCR5 antagonist therapy is being considered 1

Testing Methods

Two primary approaches are used to determine HIV tropism:

1. Phenotypic Testing

• Enhanced Sensitivity Trofile Assay: Considered the gold standard
• Uses patient-derived env sequences to create pseudoviruses that are tested for their ability to infect cells expressing either CCR5 or CXCR4 coreceptors
• Can detect minority CXCR4-using variants when present at 5-10% of the viral population 2
• Requires a viral load of at least 1,000 copies/mL 2

2. Genotypic Testing

• Based on sequencing the V3 loop of the HIV envelope gene
• Methods include:
  • V3 population genotyping
  • Ultradeep sequencing for detecting minority variants
  • Bioinformatic algorithms like geno2pheno and PSSM to predict tropism 1
• Advantages: Greater accessibility, lower cost, and faster turnaround time 1
• Limitations: Lower sensitivity but good specificity for detecting CXCR4-using variants 3

Clinical Application

The European Consensus Group recommends:

1. When to test: Before initiating CCR5 antagonist therapy
2. Preferred methods: Enhanced sensitivity Trofile assay or V3 population genotyping
3. Laboratory requirements: Adequate quality assurance measures
4. Clinical collaboration: Close partnership between HIV clinicians and virologists 1

Impact on Treatment Decisions

• Maraviroc is FDA-approved for treatment-experienced adults with only CCR5-tropic virus detected 4
• Patients with CXCR4-using or dual/mixed-tropic virus should not receive CCR5 antagonists, as these drugs would be ineffective and could lead to treatment failure 1
• In clinical trials, patients with CCR5-tropic virus showed significantly better virologic response to maraviroc (median viral load reduction of -2.4 log10) compared to those with non-R5 virus (reduction of -1.0 to -1.2 log10) 5

Epidemiological Considerations

• Most patients in early HIV disease have R5 variants
• The prevalence of CXCR4-using variants increases as disease progresses
• Higher CD4 cell counts and lower viral loads are associated with CCR5 usage 6
• Viral clade does not significantly influence coreceptor usage 6

Common Pitfalls and Caveats

1. Minority variants: Standard genotypic methods may miss minority CXCR4-using variants that could lead to treatment failure
2. Sample quality: Inadequate viral load (<1,000 copies/mL) may lead to amplification failure
3. Tropism shifts: Patients may experience a shift in viral tropism during treatment
4. Resistance mechanisms: Treatment failure can occur through either outgrowth of pre-existing X4 variants or through resistance mutations in R5 variants 7

Laboratories performing HIV tropism tests should implement appropriate quality assurance measures to ensure accurate results that will guide proper treatment decisions.