HIV-1 Resistance to CCR5 Inhibitor Without Fitness Loss
Author Information
Author(s): Anastassopoulou Cleo G, Marozsan Andre J, Matet Alexandre, Snyder Amy D, Arts Eric J, Kuhmann Shawn E, Moore John P
Primary Institution: Weill Medical College of Cornell University
Hypothesis
Does the development of resistance to the CCR5 inhibitor AD101 incur a fitness cost for HIV-1?
Conclusion
HIV-1 can develop resistance to the CCR5 inhibitor AD101 without a significant loss in its ability to replicate.
Supporting Evidence
- AD101 resistance was not associated with a fitness loss in head-to-head competition assays.
- The resistant phenotype remained stable after 20 passages without the selecting compound.
- Amino acid substitutions in the V3 region of gp120 that confer resistance do not impair fitness in the resistant isolate.
Takeaway
This study found that when HIV-1 becomes resistant to a drug called AD101, it doesn't get weaker and can still grow well.
Methodology
The study used a growth-competition assay with dual infections of molecularly cloned viruses to assess the fitness of HIV-1 strains.
Limitations
The study primarily focused on in vitro conditions, which may not fully represent in vivo scenarios.
Digital Object Identifier (DOI)
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