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Concern of NNRTI transmission during chronic infection
Aug 8, 2007

(Sorry to resubmit this question Doc, but I mispoke earlier. His doctor recommended taking him off tx. altogether 18 months ago.) Previous - I have a relatively complex question regarding potential reinfection with a NNRTI resistant mutation. I am HIV chronically infected for well over 5 years. I'm doing well on HAART (Epzicom and Viramune) with undetectable viral load and CD4 counts over 800. I have been abstinent for many years, as to not spread the virus or put myself at risk for additional STIs. I recently, however, met a positive partner and began dating. I am well informed on the data suggesting chronic infection confers some protection against reinfection. In a moment of impulsivity, however, my new date and I had UAI. He informed me that he was on Sustiva and two nukes for three years with complete viriologic suppression and CD4 counts over 1200. However, his doctor recommended treatment interruption approximately 18 months ago. Since then his viral load climbed very slowly to its current 20,000 level. His CD4 cells remain over 500. The problems lies in his doctor stopping his regimen at once, disregarding the caution about the extended half-life of Sustiva. He was completely unaware of the risks for developing a NNRTI mutation following such a protocol. He is Caucasian and maintained a relatively low viral load for some time after discontinuation of HAART. My question is, in the chance that he did develop the NNRTI mutation, am I now at risk for its transimission to me on my current Epzicom/Viramune regimen. This episode represented a single encounter, but it was UAI. I realize this was entirely irresponsbile, but self-recrimination will serve no purpose now. My ID follow-up is not for 3 months. Should I take any preventive steps or wait that long to see what happens with my numbers?



Response from Dr. Sherer

Yes, you should take preventive measures...whatever it will take to discourage you from further doing UAI, which I am guessing stands for unprotected anal intercourse. You obviously know that, but it is the first lesson from this episode, and a hard one.

On the bright side are the long odds that all the events that worry you have all happened at the same time to conspire to result in your acquisition of an NNRTI-resistant strain, and the relative infrequency of "super-infection" of a second HIV strain in a person already infected with one, and the fact that you are undetectable on a regimen that might be expected to suppress a potentially transmitted virus. Still, you will help yourself to avoid this terrible uncertainty in future by playing with latex. So rather than self recrimination, just some sober resolve will do fine. Don't beat yourself up, just deal with it and find alternatives that work for you.

What you suggest is possible - an NNRTI mutant virus might have arisen because of the way in which his regimen was stopped, but that was 18 months ago, and while some NNRTI mutations are persistent, more commonly they become minority species after 1 year of discontinuation.

And even if they did persist in a minority species in your partner, that variant may not necessarily have joined the swarm infecting his gonads. There is some variation between plasma virus and genital secretion virus.

However, since what you suggest is POSSIBLE, you can certainly return to your doctor's sooner than three months and request repeat viral load and CD4 cell count testing, as well as a genotype if the value is above 1,000, in order to find out whether any such thing happened from a single UAI encounter, from which the likelihood of transmission is estimated to be in the range of 1:300. You can report to him or her whether you have had any signs or symptoms of acute HIV infection. And you can measure your viral load for any sudden unexpected increases, and see if your past genotype persists, or new ones have suddenly emerged unexpectedly, suggesting recent super-infection.

Finally, as above, super-infection is remarkably uncommon, and some would say rare. It appears that HIV has some immunologic properties that decrease the likelihood of super-infection. Researchers in North America with the predominant B viral strain have struggled to prove cases of super-infection, even in the setting of multiple high risk partners. The literature is full of stories of discordant couples who had unprotected sex for a decade or more without transmitting the virus, and of couples in which both individuals are HIV infected, but no super-infection occurs after years of unprotected sex.

The highest 'rate' that I have seen is an observational cohort from Kenya in which superinfection occured to 8 individuals in 54 discordant couples over a two year period, and we have to be careful about making too many comparisons between HIV transmission in Africa and in the north, as there are many additional cofactors in HIV transmission that may vary in these different settings.

My advise to you is to talk to your doctor about these events, repeat your viral load and genotype, and discuss this email with him or her.

Finally, you asked also whether other preventive measures might be useful. There is some evidence to suggest that post-exposure prophylaxis with ART might decrease the risk of transmission following exposure if instituted promptly, eg within 4 hours, and not longer than 72 hours following exposure in a person who is not HIV infected. There is much less data concerning the possiblity of PEP in people who have HIV infection in order to prevent a superinfection. Your current therapy is suppressing your virus well. It is reasonable to think that it would have a similar action against a transmitted virus, even one with a single mutation, because of the presence of three active drugs in your regimen.

Resistance from clinical trial?
Will a blip in viral load cause a drop in CD4??

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