What do these other mutations mean?

Question

Hi,

First of all, thanks for all the helpful advise and information you've given on this site. It's been a great help for someone newly infected.

I just received the results of my resistance test.

The Genotypic Resistance Interpretation Algorithm showed no NRTI or NNRTI Resistance Mutations. It however showed the following "Other Mutations": T39A, D123E, I135T, D177E, R211K

The Genotypic ARV Resistance Report (RT Inhibitor) also showed no NAMs, NRTI or NNRTI Mutations. But did show "RT Other Mutations" such as T35V, K39A, E43K, E122K, S123E, I135T, T173K, K174Q, M178I, I200T, A207Q, R211K, R238K, E245V, A254V, 255N, 256D, 257I, 258Q and 259K

I am treatment naive and the test was taken 6 weeks after seroconversion.

My question is: what do these other mutations mean? Are they still a potential source of complication to treatment or be a cause of concern generally?

Thank you.

Answer

Thank you for this important and detailed question. One detail that might also have helped is your current viral load. I would guess that it is quite high, i.e. in the hundreds of thousands or higher.

It may be less alarming to understand that these "mutations" are better named "polymorphisms". As this name implies, HIV is remarkably heterogeneous, i.e. HIV comes in many shapes (poly morphisms). The process of HIV replication is highly error-prone. There are 10 billion new virions (viral particles) being produced daily, and every 10,000 cycles a "mutation", or rather a "polymorphism" is produced; hence HIV, which has a small genome, produces single mutations at every amino acid locus daily, and many pairs of mutations.

As you can see, rather than being infected with a single virus with uniform genetic composition, a person with HIV is infected with a 'swarm' of viral cousins, and it is somewhat difficult to define the 'normal' genotype in this environment.

More important, then, are the mutations that we know cause reduced susceptibility to currently available drugs. In your case, your genotype interpretation, with which I agree, suggests that you are fully susceptible to all drugs, i.e. you have a 'wild-type' virus. All of the alarming-looking polymorphisms in the list above amount to very little.

Your question is still important, however, because we are still learning about the role of various mutations at sites that have not appeared to be clinically significant.

For the time being, you can rest assured that you have wild type virus that should have excellent responsiveness to ART if and when that time comes.

I urge you to talk to your doctor about your concerns and these comments.