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Pre-natal HART Induced-Resistance and Ethnicity Issues
Nov 20, 2004

Hello, Doctor:

I have several questions, the answers to which I can't seem to find elsewhere.

By way of introduction, I am a 38 y.o. Caucasian male, and my wife is a 32 y.o. Asian. She was diagnosed HIV+ late-2002 during a prenatal STD scan and was prescribed a 2-drug regimen. At time of delivery, her v.l. was undetectable. I was diagnosed later in May '03 and believe that I was infected in 2001. After our sons birth, our infectious diseases specialist in Bangkok advised her to suspend treatments and allow the disease to progress to the CDC's current recommended HART trigger points. He advised that I adopt a similar treatment strategy. Our numbers are good but seem to me to oscillate significantly quarter-to-quarter: my wife's mean(st.dev) numbers are CD4 658(113) and VL 6k(3.7k), with current values of 820 and 9.8k; my mean/(st.dev) numbers are 677(134) and 21.3k(4.6K), with current values of 660 and 21.8k.

Now to my questions: (1) Should we be concerned that my wifes short-term therapy might have produced a drug resistant strain of the virus? How might that limit future drug therapies/ combinations, given that AZT seems to figure prominently in most combinations? (2) If viral mutation is likely, what are the risks that our viruses have mixed through intercourse to create a third more lethal strain? Assume that we have been monogamous but continue to have unprotected sex. (3) In reference to my likely date of infection and our above numbers, how soon would you expect us to commence HART treatments? Ive read elsewhere in this forum that one can roughly assume a 100-count drop in CD4 per yearwhich would place us at about 3 years. (4) If (3) above is reasonable, then Im looking at a total of 6 years to commencement of HART (shorter for my wife if I infected her). Does this mean we are likely fast-progressors? If so, how do fast-progressors fare under HART relative to the overall population of patients? (5) Finally, all other factors held constant, how does ethnicity affect one's ability to withstand drug toxicity and emergence of drug resistant strains? I have heard that Asians, particularly Asian women, tend to be most susceptible to both complications..

Best wishes, FactFinder

Response from Dr. Sherer

I will address these questions in order. I would ask that you take both the questions and my answers to your doctor, so that you and your wife and he or she can discuss them at length.

I will also assume that your wife's two drug regimen was AZT + 3TC; you allude to it, but didn't say as much.

1) The good news is that resistance following pMTCT with AZT and 3TC is uncommon, in the range of 5-10%, and usually with the M184V mutation that is associated with 3TC resistance. As she was undetectable at delivery, the risk is even lower. (You may recall that 5-10% of patients on AZT+3TC as treatment were well-suppressed, i.e. those whose initial viral loads were < 10,000 copies. You didn't mention here initial viral load - if it were in that range, again the risk of mutations would be lower.)

2) As above, the chances are good that your wife did not acquire a resistance mutation during pregnancy. There is also the possibility that either or both of you acquired a resistant virus, though that also would be a low probability and would depend on where each of you were likely to have been infected, and, obviously, by whom. These are very difficult estimates to make with any precision. Superinfection appears to be an uncommon event, according to those researchers who have gone looking for it. Since it has been documented, clinicians continue to recommend using latex barrier protection for HIV+ couples. From surveys of such couples, as many as one third choose to have unprotected sex, as you have.

3&4) Your estimates are in general correct, but the best estimate will be made with your doctor after a review of all of your CD4 and viral load trends over time. I can't tell at present that you are a 'fast-progressor' from the information you have given me.

4)We are still learning about this issue. At present, there are no differences in dosing recommendations for Asians, though some are based on weight, and no striking evidence of differences in resistance patterns with non-B HIV sub-types - but the data are limited. You and your doctor will be well advised to watch the increasing number of clinical trials in Thailand and elsewhere in Asia for any evidence of altered toxicity, pharmacology, and resistance patterns.


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