Primary prevention
Pneumocystis jirovecii pneumonia (PCP)
Chemoprophylaxis against PCP is recommended for people living with HIV who have CD4 counts <100 cells/microlitre regardless of plasma HIV levels, and those with CD4 counts between 100 and 200 cells/microlitre with plasma HIV ribonucleic acid (RNA) levels above detection limits.[1]
Trimethoprim/sulfamethoxazole is the recommended prophylactic agent.[1][65][66] Alternatives, regardless of Toxoplasma gondii serostatus, include: dapsone plus pyrimethamine plus folinic acid; or atovaquone. Alternatives for adults who are seronegative for T gondii include: dapsone; aerosolised pentamidine; or intravenous pentamidine.[1] Primary PCP prophylaxis should be discontinued for individuals who have responded to antiretroviral treatment (ART) with an increase in CD4 to more than 200 cells/microlitre for 3 months or longer.[67][68]
Individuals who are receiving pyrimethamine/sulfadiazine for treatment or suppression of toxoplasmosis do not require additional prophylaxis for PCP.[1]
Toxoplasmosis
People living with HIV with CD4 counts <200 cells/microlitre should be tested for the immunoglobulin G antibody to Toxoplasma gondii soon after the diagnosis of HIV infection to detect latent infection. All people living with HIV, especially those with CD4 counts <200 cells/microlitre, should be counselled not to eat raw or under-cooked meat or raw shellfish. Cat owners with HIV whose CD4 counts are <200 cells/microlitre and who are seronegative are advised to avoid direct contact with cat faeces. Seropositive individuals with a CD4 count below 100 cells/microlitre should be prescribed prophylaxis against T gondii. Trimethoprim/sulfamethoxazole is preferred. Alternatives include: dapsone plus pyrimethamine plus folinic acid; or atovaquone. Prophylaxis against Toxoplasma should be discontinued among individuals who have responded to ART with an increase in CD4 to more than 200 cells/microlitre for more than 3 months and sustained HIV RNA below limits of detection.[1][69]
Tuberculosis (TB)
Testing for latent TB infection (LTBI) is recommended when HIV infection is first recognised.[1] Tests include:[70][71]
A tuberculin skin test (TST)
An interferon gamma release assay (IGRA)
A TB antigen-based skin test (TBST)
The diagnostic accuracy of TSTs and IGRAs are limited and the sensitivity of both declines with progressive immunodeficiency.[70][71] Decisions should not be based on TST or IGRA results alone; epidemiological, historical, and clinical information should also be considered.[1] A positive TST in a person with HIV is defined as ≥5 mm of induration at 48-72 hours. All people living with HIV 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 people living with HIV, 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]
TBSTs 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 people living with HIV, reporting that the diagnostic accuracy of TBSTs is similar to that of IGRAs and greater than that of the TST.[71]
Local guidelines should be consulted for specific regimens.[1][72][73] Preferred treatment options for LTBI in the US include the short-course, rifamycin-based regimens: rifapentine plus isoniazid once weekly for 12 weeks, daily rifampicin for 4 months, or daily isoniazid plus rifampicin for 3 months.[72][74] 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.[75] 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 people living with HIV who immediately start ART, regardless of CD4 count.[1] People with HIV who have CD4 counts <50 cells/microlitre and are not receiving ART, or have not responded to ART, or have no options for a fully suppressive ART regimen should receive prophylaxis. The preferred prophylactic agents are either azithromycin or clarithromycin. Rifabutin may be used as an alternative if the individual cannot tolerate azithromycin or clarithromycin, but drug interactions may complicate its use (and active TB should be ruled out before starting rifabutin). Before starting prophylaxis, MAC disease should be ruled out by clinical assessment and, if appropriate, by obtaining a blood culture for MAC. If blood culture is obtained, prophylaxis should be delayed until results are available to avoid the risk of drug resistance.[1] Once initiated, primary prophylaxis can be discontinued when the individual is placed on a fully suppressive ART regimen.[1]
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/microlitre is the best strategy for preventing CMV end-organ disease, in conjunction with 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. Pre-emptive therapy with either fluconazole or amphotericin-B is only recommended for those with a CD4 count <100 cells/microlitre who have a positive screening serum cryptococcal antigen test. These individuals should be carefully evaluated for cryptococcal meningitis.[1][76] 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 people living with HIV who have a CD4 count <100 cells/microlitre.[76]
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
People living with HIV residing 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] Serological testing for coccidioidomycosis is advised in people living with HIV who have previously travelled to or lived in endemic areas.[1] Annual to biannual screening with IgG and IgM serologies should be considered for asymptomatic people living with HIV currently living in endemic areas who have a CD4 <250 cells/microlitre.[1] Primary prophylaxis with fluconazole is indicated for asymptomatic people living with HIV who have a positive serological test for coccidioidomycosis and should be continued until the HIV viral load is suppressed to an undetectable level and the CD4 count is ≥250 cells/microlitre.[1] Individuals with CD4 counts ≥250/microlitre 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]
Histoplasmosis
For people living with HIV, with CD4 count <150 cells/microlitre, and residing in areas with a hyperendemic rate of histoplasmosis (>10 cases per 100 patient-years), primary prophylaxis with itraconazole is recommended.[1] In people receiving ART, primary prophylaxis with itraconazole can safely be discontinued when the individual’s HIV viral load is undetectable and the CD4 count has been ≥150 cells/microlitre for 6 months.[1] If the CD4 count falls to <150 cells/microlitre, prophylaxis should be restarted.[1]
Secondary prevention
Tuberculosis (TB)
Identifying and treating TB promptly is the most effective TB control measure. Individuals with known or presumed TB should remain physically separated from other individuals and especially those with HIV infection. Crucial preventive activities include intensified case finding such as active identification of TB among people with HIV, screening their household members for active TB, and reporting TB.[46][285]
Disseminated Mycobacterium avium complex (MAC)
Individuals 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 more than 100 cells/microlitre after ART can discontinue secondary prophylaxis. Chronic maintenance therapy/secondary prophylaxis may be reintroduced if CD4 count decreases to levels consistently below 100 cells/microlitre 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/microlitre to greater than 200 cells/microlitre for more than 3 months as a result of ART. Prophylaxis should be reintroduced if the CD4 count decreases to below 200 cells/microlitre.
If PCP recurrence occurs at a CD4 greater than 200 cells/microlitre while the individual is on ART, lifelong prophylaxis should be considered.
Toxoplasmosis
After completion of treatment, secondary prophylaxis should be initiated.
Individuals who remain asymptomatic have a low risk of recurrence of toxoplasmic encephalitis and, if their CD4 count remains above 200 cells/microlitre after ART (for >6 months), can discontinue secondary prophylaxis. However, secondary prophylaxis should be reintroduced if the CD4 count decreases to below 200 cells/microlitre.[286]
Cryptococcal meningitis
Chronic maintenance therapy for cryptococcosis may be discontinued in individuals who have received therapy for a minimum of 1 year after successful treatment of cryptococcosis, have CD4 counts ≥100 cells/microlitre, and have undetectable viral loads on ART for >3 months. Maintenance therapy should be resumed if the CD4 count decreases to below 100 cells/microlitre.[1]
Cytomegalovirus (CMV)
For individuals with a sustained increase (3-6 months) in the CD4 count to >100 cells/microlitre in response to ART, secondary prophylaxis can be discontinued. Chronic maintenance therapy is not routinely recommended for gastrointestinal or pulmonary disease.[1][287]
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.[288]
Secondary prophylaxis with oral itraconazole is recommended for individuals with a history of severe disseminated histoplasmosis or CNS involvement to prevent relapse.
Secondary prophylaxis with itraconazole can be discontinued in individuals who have completed at least one year of antifungal therapy, are on effective ART, have sustained CD4 counts >150 cells/microlitre for at least 6 months, have undetectable or very low Histoplasma antigen levels (<2 ng/mL) in urine and serum, and have negative blood cultures for Histoplasma capsulatum.
If the individual’s CD4 count falls below 150 cells/microlitre or ART is no longer effective, secondary prophylaxis should be resumed.
Lifelong suppressive therapy with itraconazole may be required in individuals with irreversible immunosuppression.
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