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In general, decisions about prophylaxis of opportunistic infections are based on the CD4 count, other evidence of severe immune suppression (eg, oral candidiasis), and a history of having had the infection in the past In the era prior to HAART, patients who started taking prophylactic regimens were maintained on them indefinitely However, studies have shown that in patients with robust improvements in immune function as measured by increases in CD4 counts above the levels that are used to initiate treatment prophylactic regimens can safely be discontinued Primary prophylaxis for Pneumocystis pneumonia should be offered to patients with CD4 counts below 200 cells/mcL, a CD4 lymphocyte percentage below 14%, or weight loss or oral candidiasis Patients with a history of Pneumocystis pneumonia should receive secondary prophylaxis until they have had a durable virologic response to HAART for at least 3 6 months and maintain a CD4 count of > 250 cells/mcL Regimens for prophylaxis are trimethoprim-sulfamethoxazole, dapsone, atovaquone, and aerosolized pentamidine (Table 31 6) Trimethoprim-sulfamethoxazole is inexpensive, widely available, and the most effective agent for prophylaxis In two studies comparing once-daily double-strength trimethoprim-sulfamethoxazole with aerosolized pentamidine for primary and secondary prophylaxis of Pneumocystis pneumonia,

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Drug Trimethoprim-sulfamethoxazole Dapsone Dose One double-strength tablet three times a week to one tablet daily 50 100 mg daily or 100 mg two or three times per week Side Effects Rash, neutropenia, hepatitis, Stevens-Johnson syndrome Anemia, nausea, methemoglobinemia, hemolytic anemia Limitations Hypersensitivity reaction is common but, if mild, it may be possible to treat through Less effective than above Glucose-6-phosphate dehydrogenase (G6PD) level should be checked prior to therapy Check methemoglobin level at 1 month Less effective than suspension trimethoprimsulfamethoxazole; equal efficacy to dapsone, but more expensive Apical Pneumocystis jiroveci pneumonia, extrapulmonary P jiroveci infections, pneumothorax

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Pneumocystis pneumonia was significantly less likely to develop in patients randomized to receive trimethoprim-sulfamethoxazole Bacterial infections (eg, pneumonia, sinusitis) are also less likely to develop in patients who receive trimethoprim-sulfamethoxazole Common side effects with trimethoprim-sulfamethoxazole are fever, rash, and nausea and vomiting Trimethoprim-sulfamethoxazole is dosed as one double-strength tablet three times a week to once daily Patients in whom mild rashes develop on this regimen may be treated with diphenhydramine (25 50 mg every 4 hours) However, clinicians and patients must watch carefully for signs of Stevens-Johnson syndrome Some clinicians are also using desensitization regimens to overcome allergic reactions Reports suggest that desensitization may be successful in 40% of cases Dapsone is a second-line prophylactic agent with minimal side effects As is the case with trimethoprim-sulfamethoxazole, it is inexpensive and widely available It may be used in patients with an allergic reaction to trimethoprimsulfamethoxazole Before prescribing dapsone, clinicians should make certain that the patient is not glucose-6-phosphate dehydrogenase deficient, since such patients are at high risk for developing hemolytic anemia with dapsone therapy Patients taking dapsone concomitantly with didanosine should take the dapsone at least 2 hours prior to the didanosine since dapsone is not absorbed well in the neutral pH stomach environment created by the didanosine buffering agent Finally, atovaquone may be an option for individuals intolerant of other systemic therapies, but it appears to be less effective It is available only as an oral suspension (1500 mg daily) and must be taken with food to promote absorption Finally, aerosolized pentamidine can be used if no systemic agents can be tolerated Its disadvantages are expense (approximately $100 for one treatment per month) and decreased effectiveness in the apical and peripheral areas of the lung Cases of extrapulmonary Pneumocystis infections in patients receiving aerosolized pentamidine have also been reported Aerosolized pentamidine may also increase the incidence of pneumothorax in patients with a history of Pneumocystis infection, although this complication is rarely seen in the current treatment era.

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