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Accuracy of resistance tests?
Jun 14, 2007

Is it possible for two people who were infected by the same strain to have different drug resistances? I was infected in 2003 and my partner was unfortunately infected by me in 2006 (I was the only person HIV+ person with whom he had any kind of intimate contact within the 6 months prior to him being infected). I am resistant to certain drugs (those within the same category Sustiva falls under) but my partner is not resistant to anything.

Does resistance change over time? Could our resistance tests possibly be wrong? Does this make us candidates for super-infection?

Thank you for your help.

Response from Dr. Sherer

My first suggestion is that you and your partner take your clinic records, and particularly the results of your resistance tests, to your physician(s) for a better informed approach to the questions you are asking. I lack some information that might be useful, so I suggest that you take these comments for that discussion.

For example, on what basis are you certain of being infected in 2003? Was a resistance test done when you were first found to be HIV positive, and, if so, what were the results? Also of use in your case would be the various treatment regimens that you have received, and the results of all of the resistance tests done during the course of your care.

Regarding your partner, I gather that he or she has a genotype that shows 'wild type', i.e. without significant resistant baseline mutations. Still, the actual genotype report might be useful for anwering this question to review the polymorphisms, if any, that were present, and to compare them to your most recent and past genotype reports.

Also, in order to address these questions, I would apologize for any implication of mistrust that might result, and then I would explore the possibility that your partner might have acquired the virus from another source, in spite of the history that you provide. In general, it is often difficult to be certain as to the source of HIV.

And now to your questions. As you are aware, an individual is infected with a viral 'swarm' rather than with a single clone of HIV. This swarm evolves over time with a variety of mutations known as polymorphisms. One of the weaknesses of our current genotype tests is that they show the results for the dominant HIV clone, i.e. that is present in >20% of cells. However, they will miss minority clones that are present in <20% of cells. This fact alone may explain the discrepancy in the resistant tests that you are describing. That is, if you were the source of your partner's virus in 2006, as you suggest, and you were resistant to the NNRTIs, your partner may have acquired that virus along with the wild type, but it may not have been detected by the genotype assay because it was overgrown by the more 'fit' wild type virus that was also acquired at the same time.

Resistance test results will change over time, depending on the pressure being exerted on the virus by the current regimen of antiretroviral drugs, but once resistance mutations have been acquired, they are not 'lost'. This is why HIV doctors describe the virus as unforgiving - it does not let us forget our mistakes, and it does not loose the ability to circumvent the actions of ART drugs once resistance mutations have developed.

However, resistance test results change in response to changing drug treatments, which is why its so important for patients to understand the concept of 'archived resistance'. For example, you are now resistant to Sustiva, but if your current drug treatment does not include Sustiva or another NNRTI, then your current resistance test may not show that you have NNRTI resistance, because only a minority of clones will have the mutation that is associated with NNRTI resistance. If you obtain an resistance test now, while you are on a PI-based regimen, it may not show the NNRTI mutation. However, if your were to try taking a Sustiva-based regimen again, those NNRTI reistant clones would rapily emerge as the dominant species, the regimen would fail, and your next resistance test would show NNRTI resistance. Hence we speak of 'archived resistance', in which a minority of clones retain NNRTI resistance. This is why accurate interpretation of resistance test results requires a complete history of past ART treatments, and treatment responses.

The facts that you present do not make you and your partner greater candidates for super infection than other people with HIV, but super infection, i.e. the acquisition of a second strain of HIV, is real and clearly well documented. Given what you say, it is a potential problem for you and your partner, so you should continue to use barrier protection to prevent super-infection.

So, to summarize:

- your partner could have acquired the virus from you, in spite of the differences in the genotype, and closer scrutiny of the exact test results could help to make that more or less likely;

- it is difficult to establish with certainty when HIV infection occured, and the exact source of the infection, and so the possibility of an alternate source of HIV in your partner should be considered'

- HIV is unforgiving and does not 'forget' or relinquish resistance mutations once they have occurred, BUT resistance tests do change and may mislead a clinician by failing to show the presence of one or more mutations that have been 'archived' in a minority population of virus

- HIV superinfection is well-documented and is a potential threat to you and your partner. I advise using latex barrier protection while your seek answers to these questions.

- and finally, talk to your doctors about these questions.


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