Opportunistic Infection Prophylaxis

PCP remains the most common life-threatening infection among U.S. residents with advanced HIV disease.

Other options for prophylaxis include the following:

	Dapsone 100 mg orally daily or 50 mg orally twice daily. (Note: These regimens do not prevent toxoplasmosis.)
	Dapsone 50 mg orally daily + pyrimethamine 50 mg orally once per week + leucovorin 25 mg orally once per week. (Note: This regimen also is effective in reducing the risk of toxoplasmosis.)
	Dapsone 200 mg orally + pyrimethamine 75 mg + leucovorin 25 mg, all once per week. (Note: This regimen also is effective in reducing the risk of toxoplasmosis.) Warning: Glucose-6-phosphate dehydrogenase (G6PD) deficiency can increase the risk of hemolytic anemia or methemoglobinemia in patients receiving dapsone. Screen for G6PD deficiency before starting dapsone. (G6PD deficiency is found in approximately 10% of African American males, and in 1-2% of males of Mediterranean, Indian, and Asian descent.)
	Aerosolized pentamidine 300 mg once per month, via Respirgard II nebulizer. (Note: This regimen does not prevent toxoplasmosis.) Warning: Aerosolized pentamidine may increase the risk of extrapulmonary pneumocystosis, pneumothorax, and bronchospasm. It increases the risk of TB transmission to others if the patient has active pulmonary tubercular disease, unless ventilation (negative pressurized facility with outside venting) is adequate. Do not use in patients in whom TB is suspected. The availability of treatment facilities offering aerosolized pentamidine may be limited.
	Atovaquone suspension 1,500 mg daily. (Note: This is also effective in reducing the risk of toxoplasmosis.) Atovaquone is more expensive than dapsone. It should be taken with high-fat meals for optimal absorption.
	TMP-SMX 1 double-strength tablet orally 3 times per week (eg, Monday, Wednesday, Friday).

Prophylaxis should be given to all patients with a history of PCP.

Primary or secondary prophylaxis can be discontinued if the CD4 count has increased to >200 cells/µL for at least 3 months in response to effective antiretroviral therapy (ART), with the following cautions:

	If the patient had PCP in the past and the episode of PCP occurred at a CD4 count of >200 cells/µL, it may be prudent to continue PCP prophylaxis for life, regardless of how high the CD4 count rises as a consequence of ART.
	If PCP prophylaxis is discontinued, the patient's clinical status and CD4 count must be observed closely to determine when to resume prophylaxis.
	PCP prophylaxis should be reinitiated if the CD4 count decreases to <200 cells/µL or the patient meets other criteria as indicated above.

TMP-SMX is the recommended agent for use during pregnancy; dapsone may be used as an alternative. Prophylaxis that includes pyrimethamine generally should be deferred until after pregnancy. During the first trimester, aerosolized pentamidine can be used, if the potential teratogenicity of oral agents is a concern.

Disseminated MAC (DMAC) is common in patients with advanced HIV disease and occurs in people with CD4 counts of <50 cells/µL.

Prophylaxis should be administered to all HIV-infected patients with CD4 counts of <50 cells/µL. Before starting prophylaxis, rule out active MAC infection by clinical assessment and, if warranted, by acid-fast bacilli (AFB) blood cultures (see chapter Mycobacterium avium Complex). Review the current drug regimen for medications that may interact with DMAC prophylaxis.

Patients should receive lifelong chronic maintenance therapy, unless immune reconstitution occurs in response to ART. See chapter Mycobacterium avium Complex.

Primary prophylaxis for DMAC can be discontinued in persons who have responded to effective ART with sustained increases in CD4 counts to >100 cells/µL for at least 3 months. Careful observation and monitoring are required, and prophylaxis should be restarted if the patient's CD4 count decreases to <50-100 cells/µL.

Secondary prophylaxis can be discontinued in patients who received at least 12 months of treatment for DMAC, are asymptomatic, and have sustained (for at least 6 months) CD4 counts of >100 cells/µL during ART.

Azithromycin is the prophylactic drug of choice during pregnancy, although some providers withhold it during the first trimester. Clarithromycin is teratogenic in animals.

Toxoplasmic encephalitis (TE) is usually is caused by reactivation of latent Toxoplasma gondii infection in patients with advanced immunosuppression (especially those with CD4 counts of <100 cells/µL). The USPHS/IDSA guidelines recommend that all HIV-infected patients be tested for toxoplasmosis immunoglobulin G (IgG) antibody soon after the diagnosis of HIV infection. Toxoplasmosis IgG-negative patients should be counseled to avoid sources of infection (see chapter Preventing Exposure to Opportunistic and Other Infections), and should be retested for toxoplasmosis IgG when CD4 counts fall to <100 cells/µL to determine whether they have seroconverted and are therefore at risk for TE. (See chapter Toxoplasmosis for more information on active disease and secondary prophylaxis.)

Prophylaxis should be administered to all HIV-infected patients with CD4 counts of <100 cells/µL who are seropositive for Toxoplasma. IgG-negative patients should avoid exposure to Toxoplasma; see "Patient Education" below.

(Note: The following options also are effective in preventing PCP.)

	TMP-SMX, 1 single-strength tablet daily.
	Dapsone 50 mg daily + pyrimethamine 50 mg weekly + folinic acid 25 mg weekly.
	Dapsone 200 mg weekly + pyrimethamine 75 mg weekly + folinic acid 25 mg orally weekly. Warning: G6PD deficiency can increase the risk of hemolytic anemia or methemoglobinemia in patients receiving dapsone. Screen for G6PD deficiency before starting dapsone. (G6PD deficiency is found in approximately 10% of African American males, and in 1-2% of males of Mediterranean, Indian, and Asian descent.)
	Atovaquone 1,500 mg orally daily, with or without pyrimethamine 25 mg daily + folinic acid 10 mg daily; however, this alternative is quite expensive.
	Neither aerosolized pentamidine nor dapsone alone provides protection against TE.

Patients should receive lifelong chronic maintenance therapy, unless immune reconstitution occurs in response to ART (see chapter Toxoplasmosis).

Primary prophylaxis for TE can be discontinued in patients who have responded to effective ART with sustained CD4 counts of >200 cells/µL for at least 3 months. CD4 counts should be monitored carefully, and prophylaxis should be restarted in patients whose CD4 counts decrease to <200 cells/µL.

Secondary prophylaxis may be discontinued if TE signs and symptoms have resolved with treatment and if patients have sustained (for at least 6 months) CD4 counts of >200 cells/µL during ART.

TMP-SMX may be used as primary prophylaxis during pregnancy. Prophylaxis that includes pyrimethamine generally should be deferred until after pregnancy, although pyrimethamine may be used with caution to treat active toxoplasmosis during pregnancy in sulfa-allergic patients.