Drs. Albrecht and Stellbrink have reiterated a common concern about the use of dihydrofolate reductase inhibitors. We do not believe, however, that folate-containing vitamin supplements should be restricted in patients receiving TMP-SMX. Pneumocystis carinii lacks a folate transport system [1-3]; therefore, host folate does not interfere with the action of agents that inhibit tetrahydrofolate synthesis. Folate-containing foods and supplements have not been restricted in the numerous studies documenting the efficacy of TMP-SMX in preventing and treating P. carinii pneumonia, and no evidence suggests that patients receiving such supplements are more likely to experience prophylaxis failure. Restricting dietary or supplemental folate intake would not improve the efficacy of TMP-SMX prophylaxis and could have adverse nutritional consequences.

Although latent infection with Toxoplasma gondii is more common in parts of Europe than in the United States, it remains true that persons without latent infection are much less likely to develop toxoplasmosis, especially if they are counseled on ways to avoid new infection. Further, in patients receiving dapsone because of intolerance to TMP-SMX, the cost of adding pyrimethamine and leucovorin to the regimen to prevent toxoplasmosis is considerable. Therefore, it may be reasonable, even in such highly endemic areas, to offer specific prophylaxis only to those patients with positive antitoxoplasma IgG antibodies. Patients who can receive TMP-SMX would not necessarily need to be tested. A cost-effectiveness analysis would be useful to determine the most appropriate strategy for highly endemic areas.

We agree that room for debate exists about the best time to initiate toxoplasmosis prophylaxis. We chose a CD4 count of 100 cells/mm³ on the basis of studies showing that toxoplasmosis usually develops in patients with lower CD4 counts [4, 5]. Recommendations that P. carinii prophylaxis be given to patients with CD4 counts less than 200 cells/mm³ were based on similar data. However, because most of the data supporting prophylaxis of toxoplasmosis come from trials of P. carinii prophylaxis in which prophylaxis was initiated at CD4 counts less than 200 cells/mm³, little is known about the most appropriate time to initiate toxoplasmosis prophylaxis. This question is irrelevant, however, for patients receiving TMP-SMX for P. carinii prophylaxis because they are already protected against toxoplasmosis.

We agree that sulfadiazine and pyrimethamine are the drugs of choice for maintenance therapy to treat toxoplasmosis. Clindamycin plus pyrimethamine form an alternative regimen, as we indicated in Table 1 of our article.