I was recently released from the hospital and am being treated for toxoplasmsosis. I am HIV-positive, but I have a CD4 count of 340, and my viral load has been undetectable for several years. I just ask, how could this happen? I've done everything right, take my meds religiously, and still get an OI. Any response would be greatly appreciated.

We are used to a threshold of 200 CD4 cells/ml for the development of the most severe opportunistic infections (OIs), but in fact there is a range of CD4 cell counts at which OIs such as toxoplasmosis (toxo) occur, and it can exceed 200 cells, and, even less commonly, 300 cells.

There are several possible explanations. First, you can look at the percent of your CD4 cells in addition to the absolute number. The value of 200 cells/ml usually corresponds to a percentage of 14%; you may find that, although the absolute number of CD4 cells was high, the percent may be closer to 14% or below, in which case your risk of an OI like toxo would have been higher.

Secondly, the immune reconstitution that occurs with ART is incomplete. Jay Levy of UCSF likened HIV-related immune deficiency to losing various letter tiles over time in a Scrabble game; when ART is started, the remaining tiles may be replenished, but the lost tiles may not be replenished, in which case, again using that analogy, if the "Z" is lost, you can never spell 'zebra' again, though you can spell "white horse with black stripes".

In other words, the immune deficiency caused by HIV is not fully repaired by ART, and their may be selective immune deficits, even in the presence of a good response to ART, as you have had. This may cause you to be susceptible to individual OIs, such as toxo.

One other possibility is that these events constitute an 'immune reconstitution syndrome', in which the immune improvement resulting from your ART actually caused the clinical syndrome of toxo to manifest itself. In this scenario, you had a small focus of CNS toxo when you were diagnosed with AIDS, but it was sub-clinical, and only when ART was instituted and an inflammatory response to the toxo developed did the clinical syndrome occur.

I suggest that you talk to your doctor about each of these possibilities, as only he or she is close enough to your whole clinical history to know which might have contributed to your specific situation.

The good news about having toxo is that it is treatable and further events can be prevented, once the acute episode has been treated, with suppressive therapy. Again, you and your doctor should discuss the way in which you will manage this.