It was gratifying to find such a complete overview of the prophylaxis and treatment of opportunistic infections in Annals [1, 2]. I would like to add a few comments about the treatment and prophylaxis of toxoplasmosis and pneumocystosis.

Trimethoprim-sulfamethoxazole (TMP-SMX) has proved to be the most efficacious drug for the prevention of both pneumocystosis and toxoplasmosis. Sulfamethoxazole and trimethoprim act by sequential and synergistic blockage of folic acid metabolism. Accordingly, folic acid can reverse the action of TMP-SMX. In my experience, high to excessive doses of multivitamins are a popular adjuvant therapy among persons with human immunodeficiency virus (HIV) infection. It should be remembered that many of the best-selling vitamin supplements in the United States (compared with many of the European products) contain substantial amounts of folic acid that will probably interfere with the action of TMP-SMX. Patients receiving TMP-SMX should be questioned about their use of vitamins and should be advised not to use supplements containing folic acid.

Because overt toxoplasmosis is almost always the result of reactivation of latent disease, not of primary infection, the risk in a given population correlates directly with the antibody prevalence in that population. In Europe, the seroprevalence is considerably higher than that in the United States and actually approaches 90% in such cities as Paris and Berlin. Accordingly, toxoplasmosis is a much greater problem in France and Germany than in the United States. Primary toxoplasmosis prophylaxis should be routinely administered in these countries. Neither the Centers for Disease Control and Prevention nor the U.S. Public Health Service has yet recommended routine use of primary prophylaxis against toxoplasmosis. Gallant and colleagues [1], however, after reviewing the current literature, concluded that primary prophylaxis for toxoplasmosis should also be recommended to U.S. patients with CD4 counts of less than 100 cells/mm³ who have a positive test result for antitoxoplasma IgG [1]. I am not sure how the authors determined the cutoff value of 100 cells/mm³. Although most patients at the time of diagnosis of toxoplasmosis have fewer than 100 cells/mm³, prophylaxis must begin when patients are at greatest risk for disease development and not after disease is already present. Three months before diagnosis, patients often have much higher CD4 counts. A French study found a mean CD4 count of 87 ±78 cells/mm³ in patients tested 3 months before a diagnosis of toxoplasmosis (Eliaszewics M, Lecomte I, de Sa M. International Conference on AIDS, 1990). We also found that patients with fewer than 150 cells/mm³ have the greatest risk for developing toxoplasmosis and have a risk equal to that of patients with fewer than 50 cells/mm³ [3]. We therefore recommend starting primary prophylaxis in seropositive patients who have CD4 counts less than 150 cells/mm³.

In his essay on therapeutic options for toxoplasmosis, Dr. Kovacs [2] concluded that clindamycin "is clearly an effective alternative, but whether it is as safe or effective as pyrimethamine plus sulfadiazine has not been determined." A European trial that included 342 patients randomly assigned to receive either clindamycin plus pyrimethamine or sulfadiazine plus pyrimethamine has undoubtedly proved that clindamycin plus pyrimethamine is as effective (and produces as many side effects) as sulfadiazine plus pyrimethamine for the short-term treatment of toxoplasmosis [4]. Four trials, however, have shown that clindamycin is much less effective than sulfadiazine for secondary prophylaxis [5]. This apparent discrepancy is probably best explained by the fact that clindamycin does not cross the blood-brain barrier in sufficient amounts unless this barrier is severely damaged. In patients with acute toxoplasmosis, the blood-brain barrier is altered sufficiently to allow adequate amounts of clindamycin to enter the cerebrospinal fluid and to reach the brain. After the infection is controlled, the blood-brain barrier heals and subsequently prevents clindamycin from reaching the cerebrospinal fluid. Accordingly, I believe clindamycin is an excellent drug for the treatment of toxoplasmosis, but it should not be the first choice for primary or secondary prophylaxis.