• Antiretroviral therapy: suppresses viral replication results in immune reconstitution
• Prophylaxis of opportunistic infections
• Prevent exposure to opportunistic pathogens
by slow intravenous infusion with careful monitoring. In patients with moderate or mild PCP a combination of clindamycin and primaquine has proven clinical efficacy and is an alternative first choice for those patients who have a previous history of severe co-trimoxazole hypersensitivity. Side-effects of rash and diarrhoea are frequent.
In patients presenting with severe hypoxaemia high-dose adjunctive corticosteroid therapy is indicated and has been shown in clinical studies to reduce both mortality and morbidity
Alternative second-line therapies include dapsone with trimethoprim, trimetrexate with folinic acid or Atovaquone, a hydroxy-naphthoquinone. The efficacy of atovaquone has only been established in mild to moderate P. carinii infection. Like trimetrexate it is probably less effective than co-trimoxazole but it is less toxic. New formulations have improved atovaquone's bioavailability but it still should not be given to patients with malabsorbtion conditions, previous severe diarrhoea or those not taking oral nutrition. Due to acquired resistance, where possible atovaquone should not be given as single-agent therapy. It is commonly combined with intravenous pentamidine as an effective second-line treatment.
Prophylaxis for PCP pneumonia is essential after a first attack (secondary prophylaxis) but is also recommended for all patients once their CD4 cell counts falls below 200 X 106/l (primary prophylaxis). The risk of a first episode PCP below this CD4 count level in patients not on antiretroviral therapy is estimated to be 18% at 12 months for those who are asymptomatic, rising to 44% for those who have early symptomatic disease (for example, oral candida, fever). Co-trimoxazole 960mg given by mouth daily or three times per week is the most effective agent. In patients who are intolerant, alternative regimens include oral dapsone 100 mg with pyrimethamine 25mg daily or three times per week, atovaquone 1500mg daily or nebulised pentamidine. Dose of the latter depends on the nebuliser system: with a Respirgard II nebuliser the recommended regimen is 300mg every four weeks. In patients with more advanced disease and CD4 counts less than 100 X 106/l, 300mg given every two weeks should be considered in view of the high failure rate of the monthly regimen.
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