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Risks Associated with PEP and Resistance
Jan 23, 2006

Dr. Sherer, I have recently finished a 30 day course of PEP (combivir 2X day with strict adherence), and I was discussing with my boyfriend (HIV+) the risks of resistance without adherence.

In a situation such as mine, where I had an exposure and started PEP within the recommended time frame, there is still a small chance that I could seroconvert and become positive.

If this were the case, would the original 30 days of PEP have any associated risks of resistance developing? Or if seroconversion were to happen after PEP was discontinued, would there be no risk of developing resistance?

Also, if I were to become positive, would there be any benefit to starting treatment within weeks of seroconversion, or would it be more beneficial to wait for my CD4 count to drop below 350 (as seems to be the case with most people who aren't diagnosed until later)?

Response from Dr. Sherer

The chance that you would experience such a double negative, i.e. a PEP failure AND the development of drug resistance due to the use of a PEP regimen like combivir is extremely small. This is particularly true for the NRTIs, for which resistance develops after multiple steps over a period of weeks to months. Resistance to 3TC can occur more rapidly, i.e. in days, so the possibility of the development of resistance can't be eliminated entirely. Still, the available evidence to date suggests that you are less likely to develop HIV infection following exposure if, as you have done, you take PEP faithfully.

Whether there is benefit to treatment shortly after seroconversion, as compared to waiting until the CD4 cell count is 350, is unknown, and thus an important matter for research. I would encourage you to consider entering a research trial that is addressing this question - but there is no good answer at present. (For research trials in acute HIV infection, you can call the NIH/NIAID hotline, 1-800-trialsA).


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