However, in later stages, HIV can evolve to use CX

However, in later stages, HIV can evolve to use CXCR4, making Leronlimab ineffective. Please explain


ChatGPT said:

Yes! Over time, HIV can evolve to switch from CCR5-tropic (R5) to CXCR4-tropic (X4) or dual/mixed tropic (using both receptors). This shift can make Leronlimab ineffective. Here's why:

1. Natural Evolution of HIV Tropism
Early Infection: The majority of new HIV infections (~60-70%) involve CCR5-tropic (R5) HIV, meaning the virus primarily uses the CCR5 co-receptor to enter CD4+ T cells.
Later Stages of HIV: As the infection progresses, mutations in the virus can cause a shift toward CXCR4-tropic (X4) HIV or a dual/mixed tropic (D/M) strain that can use both CCR5 and CXCR4.
2. Why Does This Happen?
Selective Pressure: HIV is highly adaptable. If a patient receives CCR5-targeting treatments (like Leronlimab or Maraviroc), R5-tropic HIV is suppressed, but any pre-existing CXCR4-tropic virus may continue to replicate and become dominant.
Immune System Decline: Over time, as CD4+ T cell counts drop and the immune system weakens, the virus may adapt to use CXCR4, which allows it to infect a broader range of T cells and potentially accelerate disease progression.
3. How Does This Impact Treatment?
Tropism Testing: Before using Leronlimab, doctors perform an HIV tropism test to check whether the patient’s virus is R5-tropic, X4-tropic, or dual/mixed tropic.
If Tropism Changes: If a patient starts with R5-tropic HIV but later shifts to X4 or dual/mixed tropic HIV, Leronlimab will no longer be effective.