Prophylaxis against opportunistic infection (OI) is treatment given to HIV-infected individuals to prevent either a first episode of an OI (primary prophylaxis) or the recurrence of infection (secondary prophylaxis). Prophylaxis is recommended to prevent three important OIs: Pneumocystis jiroveci pneumonia (PCP), Mycobacterium avium complex (MAC), and toxoplasmosis. Prophylaxis also is recommended to prevent tuberculosis (TB) in patients with latent Mycobacterium tuberculosis infection (see chapter Latent Tuberculosis). In endemic regions, prophylaxis against Histoplasma capsulatum and Coccidioides species is advised. And in some situations, prophylaxis against other OIs may be reasonable; see the OI prevention recommendations of the U.S. Public Health Service and the Infectious Diseases Society of America (USPHS/IDSA) (reference below) for additional information.
PCP remains the most common life-threatening infection among U.S. residents with advanced HIV disease.
Other options for prophylaxis include the following:
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:
TMP-SMX is the recommended agent for use during pregnancy; dapsone may be used as an alternative. Some experts recommend high dose folate supplementation (e.g., 4 mg daily) for pregnant women receiving TMP-SMX, because TMP-SMX may worsen folate deficiency. Prophylaxis that includes pyrimethamine generally should be deferred until after pregnancy. During the first trimester, aerosolized pentamidine (which is not systemically absorbed) can be used if the potential teratogenicity of oral agents is a concern.
Mycobacterium avium complex (MAC) is common among patients with advanced HIV disease and it 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). Also rule out active TB prior to starting any rifabutin-containing regimen for MAC prophylaxis. Review the current drug regimen for medications that may interact with MAC prophylaxis.
Rifabutin 300 mg once daily (Note: Rifabutin has significant interactions with many drugs; certain nonnucleoside reverse transcriptase inhibitors and protease inhibitors should be avoided or dosage adjustment of rifabutin may be required. See chapter Drug-Drug Interactions with HIV-Related Medications.)
Patients should receive lifelong chronic maintenance therapy, unless immune reconstitution occurs in response to ART. See chapter Mycobacterium avium Complex.
Primary prophylaxis for MAC 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 cells/µL.
Secondary prophylaxis can be discontinued in patients who received at least 12 months of treatment for MAC, are asymptomatic, and have sustained (for at least 6 months) CD4 counts of >100 cells/µL on ART. Secondary prophylaxis should be reintroduced if the CD4 count decreases to <100 cells/µL.
Azithromycin is the prophylactic drug of choice during pregnancy, although evidence for its safety in the first trimester is limited. Clarithromycin is teratogenic in animals
Toxoplasmic encephalitis (TE) 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 recommendations state that all HIV-infected patients should be tested for Toxoplasma immunoglobulin G (IgG) antibody soon after the diagnosis of HIV infection. Toxoplasma 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 Toxoplasma IgG when CD4 counts fall to <100 cells/µL to determine whether they have seroconverted and are therefore at risk of 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.)
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 <100-200 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 on ART. Secondary prophylaxis should be reintroduced if CD4 counts drop to <200 cells/µL.
TMP-SMX may be used as primary prophylaxis during pregnancy. Risks of TMP-SMX in the first trimester must be balanced against the risks of reactivated toxoplasmosis. Some experts recommend high dose folate supplementation (e.g., 4 mg daily) for pregnant women receiving TMP-SMX, because TMP-SMX may worsen folate deficiency. Pyrimethamine has been associated with birth defects in animal studies, but limited data in human studies have not shown an increased risk. Secondary prophylaxis generally should be provided using the same guidelines as for nonpregnant women.
Infection with Histoplasma capsulatum is common in several geographic areas including the Ohio and Mississippi River Valleys, as well as parts of Central and South America, Asia, and Africa. Symptomatic disease can occur via primary infection or reactivation of previously silent infection in the setting of waning cellular immunity. CD4 counts of ≤150 cells/µL, along with positive Histoplasma serology and environmental exposure, are associated with increased risk of symptomatic disease. Histoplasmosis can cause a range of clinical manifestations including respiratory, gastrointestinal, central nervous system (CNS), and cutaneous disease.
Prophylaxis can be considered for HIV-Infected patients with CD4 counts of ≤150 cells/µL who are at high risk because of occupational exposure and for those who live in an area where histoplasmosis is highly endemic. HIV-infected patients with CD4 counts of ≤150 cells/µL should be educated to avoid exposure.
Patients with a history of severe disseminated disease or CNS infection and those who have relapsed despite receiving appropriate therapy should receive long-term suppressive therapy.
Primary prophylaxis can be discontinued once CD4 counts are >150 cells/µL for at least 6 months. CD4 counts should be monitored carefully, and prophylaxis should be restarted for patients whose CD4 counts decrease to ≤150 cells/µL.
Secondary prophylaxis may be discontinued if patients have received at least 1 year of itraconazole, have negative blood cultures, have had CD4 counts ≥150 cells/µL for at least 6 months on ART, and have serum Histoplasma antigen <2 units.
Azoles should not be used during the first trimester of pregnancy because of teratogenicity concerns.
The Coccidioides species fungus is endemic to many arid regions. In the United States, it is found primarily in the Sonoran Desert in Arizona and the San Joaquin "Central" Valley in California, but also in areas of New Mexico, western Texas, Nevada, and Utah. It also is endemic to many arid regions in Central and South America. Immune response to Coccidioides species declines as CD4 counts decrease, and risk of developing symptomatic disease in endemic areas is increased when the CD4 count is ≤250 cells/µL. In HIV-infected patients, six syndromes have been described: focal pneumonia, diffuse pneumonia, cutaneous involvement, meningitis, liver or lymph node involvement, and positive serology without localized infection.
HIV-infected persons from Coccidioides-endemic areas with positive IgM or IgG serologies are at increased risk of developing active infection, especially if their CD4 counts are ≤250 cells/µL. Many experts would recommend primary prophylaxis for such patients. Annual monitoring for seroconversion of HIV-infected patients in endemic areas is prudent. Patients in endemic areas should be educated to avoid exposure.
(Note: Itraconazole has significant interactions with many drugs, including NNRTIs, PIs, and maraviroc. Dosage adjustments may be required, and some combinations may be contraindicated; consult with a pharmacist or other specialist.)
Patients who have completed initial treatment for coccidiomycosis should be considered for lifelong chronic maintenance therapy.
Primary prophylaxis can be discontinued once CD4 counts are ≥250 cells/µL for at least 6 months, but should be restarted if the CD4 count drops to <250 cells/µL.
Suppressive therapy should be continued lifelong for patients with a history of diffuse pulmonary, disseminated, or meningeal disease, as these patients are at high risk of relapse. Patients with focal coccidioidal pneumonia who have had good clinical response to antifungals can discontinue secondary prophylaxis once they have received 12 months of therapy, and have CD4 counts >250 cells/µL on ART. These patients should undergo close radiologic and serologic monitoring for recurrence.
Women who acquire coccidiomycosis in the second or third trimester of pregnancy are at increased risk of dissemination. Azoles should not be used during the first trimester of pregnancy because of teratogenicity concerns.