Primary prevention

Pneumocystis jirovecii pneumonia (PCP)

  • People living with HIV (PLWH) should receive chemoprophylaxis against PCP if they have a CD4 count below 200 cells/microliter. Prophylaxis should also be considered if CD4 cell percentage is less than 14% or if CD4 count is 200-250 cells/microliter, antiretroviral treatment (ART) is delayed, and frequent CD4 count monitoring (e.g., every 3 months) is not possible.[1]

  • Trimethoprim/sulfamethoxazole (TMP/SMX) is the recommended prophylactic agent.[1][58][59]​ Alternatives include dapsone, dapsone plus pyrimethamine plus leucovorin, aerosolized pentamidine, and atovaquone. Atovaquone, aerosolized pentamidine, and dapsone are considered to be equally effective.[1]​​ Primary PCP prophylaxis should be discontinued for patients who have responded to ART with an increase in CD4 to above 200 cells/microliter for 3 months or longer.[60][61]

  • Patients who are receiving pyrimethamine/sulfadiazine for treatment or suppression of toxoplasmosis do not require additional prophylaxis for PCP.[1]

Toxoplasmosis

  • PLWH should be tested for the immunoglobulin G antibody to Toxoplasma gondii soon after the diagnosis of HIV infection to detect latent infection, and should be counseled not to eat raw or undercooked meat and to avoid direct contact with cat feces. Seropositive patients with a CD4 count below 100 cells/microliter should be prescribed prophylaxis against T gondii. TMP/SMX is preferred, and dapsone plus pyrimethamine or atovaquone are the recommended alternatives. Prophylaxis against Toxoplasma should be discontinued among patients who have responded to ART with an increase in CD4 to above 200 cells/microliter for 3 months or longer.[1][62]

Tuberculosis (TB)

  • Testing for latent TB infection (LTBI) is recommended when HIV infection is first recognized.[1] Either a tuberculin skin test (TST) or an interferon gamma release assay (IGRA) can be used, though the diagnostic accuracy of both are limited and the sensitivity of both declines with progressive immunodeficiency.[63][64]​​​​​​ Decisions should not be based on TST or IGRA results alone; epidemiologic, historic, and clinical information should also be considered.[1] A positive TST in an HIV-infected person is defined as ≥5 mm of induration at 48-72 hours. All PLWH with a positive TST or IGRA should undergo chest x-ray and clinical evaluation to rule out active TB. Since the risk of progression to active disease is significantly higher, all PLWH, regardless of age, who have a positive TST or IGRA result but no evidence of active TB and no history of treatment for active or latent TB should be treated for latent TB infection (in the absence of other medical contraindications).[1] TB antigen-based skin tests (TBSTs) are a new class of tests that have been developed to measure the cell-mediated immunological response to M tuberculosis-specific antigens. The World Health Organization recommends that TBSTs may be used to test for latent TB infection, including in PLWH, reporting that the diagnostic accuracy of TBSTs is similar to that of IGRAs and greater than that of the TST.[64]​ Local guidelines should be consulted for specific regimens.[1][65][66][67]​​​​​ Preferred treatment options for LTBI in the US include the short-course, rifamycin-based regimens: rifapentine plus isoniazid once weekly for 12 weeks, daily rifampin for 4 months, or daily isoniazid plus rifampin for 3 months.[65][68]​​​ Potential rifamycin-induced drug-drug interactions must be carefully considered prior to treatment initiation. Daily isoniazid monotherapy for 6-9 months is an efficacious regimen recommended by the World Health Organization guidelines; however, it is associated with a higher risk of hepatotoxicity and lower treatment completion rates.[67][69]​ Regimens for those exposed to drug-resistant TB should be selected after consultation with experts or public health authorities.[1]

Mycobacterium avium complex (MAC)

  • Routine primary prophylaxis against disseminated MAC disease is no longer recommended for PLWH who immediately start ART, regardless of CD4 count.[1] Prophylaxis is only recommended for PLWH who are not on fully suppressive ART and who have a CD4 count <50 cells/microliter. The preferred prophylactic agents are either azithromycin or clarithromycin. Rifabutin may be used as an alternative if the patient cannot tolerate azithromycin or clarithromycin, but drug interactions may complicate its use. Disseminated MAC disease should be ruled out before starting prophylaxis, and active tuberculosis infection should be ruled out before starting rifabutin. 

Cytomegalovirus (CMV)

  • Prophylactic therapy is not recommended for the prevention of CMV infection. The use of effective ART to maintain the CD4 count >100 cells/microliter is the best strategy for preventing CMV end-organ disease, in conjunction with patient education about the early manifestations of disease and initiation of therapy when indicated.[1]

Cryptococcal meningitis

  • Administration of effective ART without routine antifungal prophylaxis remains the preferred strategy for preventing HIV-associated cryptococcal disease. Preemptive therapy with either fluconazole or amphotericin B is only recommended for those with a CD4 count <100 cells/microliter who have a positive screening serum cryptococcal antigen test. These patients should be carefully evaluated for cryptococcal meningitis.[1][70] In settings where antigen screening is not available, or where there may be long delays in receiving the result, the World Health Organization recommends initiating fluconazole primary prophylaxis in PLWH who have a CD4 count <100 cells/mm³.[70]

Candidiasis

  • Primary prophylaxis against mucocutaneous candidiasis is not routinely recommended, since the risks associated with the disease are relatively low and the potential benefits of antifungal prophylaxis are outweighed by drug costs, drug-drug interactions, and the risk of promoting drug resistance.[1]

Coccidioidomycosis

  • PLWH living in or visiting areas where Coccidioides are endemic are advised to avoid exposure to disturbed native soil (e.g., at building excavation sites) and to remain inside during dust storms.[1] Serologic testing for coccidioidomycosis is advised in PLWH who have previously traveled to or lived in endemic areas.[1] Annual to biannual screening with IgG and IgM serologies should be considered for asymptomatic PLWH currently living in endemic areas who have a CD4 <250 cells/microliter.[1] Primary prophylaxis with fluconazole is indicated for asymptomatic PLWH who have a positive serologic test for coccidioidomycosis and should be continued until the HIV viral load is suppressed to an undetectable level and the CD4 counts exceed 250 cells/microliter for at least 3 months.[1] Patients with CD4 counts ≥250/microliter who are virologically suppressed and live in endemic areas should be closely monitored for signs and symptoms of coccidioidomycosis while off prophylactic antifungal therapy.[1]

Secondary prevention

Tuberculosis (TB)

  • Identifying and treating TB promptly is the most effective TB control measure. Patients with known or presumed TB should remain physically separated from other patients and especially those with HIV infection. Crucial preventive activities include intensified case finding such as active identification of TB among patients with HIV, screening their household members for active TB, and reporting TB.[42][265]

Disseminated Mycobacterium avium complex (MAC)

  • Patients who remain asymptomatic after completing more than 12 months of treatment for MAC and have a sustained increase (>6 months) in their CD4 counts to greater than 100 cells/microliter after ART can discontinue secondary prophylaxis. Chronic maintenance therapy/secondary prophylaxis may be reintroduced if CD4 count decreases to levels consistently below 100 cells/microliter and a fully suppressive ART regimen is not possible.[1]​​

Pneumocystis jirovecii pneumonia (PCP)

  • Secondary prophylaxis is recommended after completion of treatment. It can be discontinued if the CD4 count has increased from below 200 cells/microliter to above 200 cells/microliter for more than 3 months as a result of ART. Prophylaxis should be reintroduced if the CD4 count decreases to below 200 cells/microliter.

  • If PCP recurrence occurs at a CD4 above 200 cells/microliter while the patient is on ART, lifelong prophylaxis should be considered.

Toxoplasmosis

  • After completion of treatment, secondary prophylaxis should be initiated.

  • Patients who remain asymptomatic have a low risk of recurrence of toxoplasmic encephalitis and, if their CD4 count remains above 200 cells/microliter after ART (for >6 months), can discontinue secondary prophylaxis. However, secondary prophylaxis should be reintroduced if the CD4 count decreases to below 200 cells/microliter.[266]

Cryptococcal meningitis

  • Chronic maintenance therapy for cryptococcosis may be discontinued in patients who have received therapy for a minimum of 1 year after successful treatment of cryptococcosis, have CD4 counts ≥100 cells/microliter, and have undetectable viral loads on ART for >3 months. Maintenance therapy should be resumed if the CD4 count decreases to below 100 cells/microliter.​[1]

Cytomegalovirus (CMV)

  • For patients with a sustained increase (3-6 months) in the CD4 count to >100 cells/microliter in response to ART, secondary prophylaxis can be discontinued. Chronic maintenance therapy is not routinely recommended for gastrointestinal or pulmonary disease.[1][267]

Mucocutaneous candidiasis

  • Secondary prophylaxis is not recommended because of the potential for resistance, cost, possibility of drug interactions, and the effectiveness of therapy for acute disease. However, it might be considered for frequent or severe recurrent episodes.[268]

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