Primary prevention
Pneumocystis jirovecii pneumonia (PCP)
Chemoprophylaxis against PCP is recommended for people living with HIV who have CD4 counts <100 cells/microliter regardless of plasma HIV levels, and those with CD4 counts between 100 and 200 cells/microliter 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 leucovorin; or atovaquone. Alternatives for adults who are seronegative for T gondii include: dapsone; aerosolized 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 above 200 cells/microliter 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/microliter 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/microliter, should be counseled not to eat raw or undercooked meat or raw shellfish. Cat owners with HIV whose CD4 counts are <200 cells/microliter and who are seronegative are advised to avoid direct contact with cat feces. Seropositive individuals with a CD4 count below 100 cells/microliter should be prescribed prophylaxis against T gondii. Trimethoprim/sulfamethoxazole is preferred. Alternatives include: dapsone plus pyrimethamine plus leucovorin; or atovaquone. Prophylaxis against Toxoplasma should be discontinued among individuals who have responded to ART with an increase in CD4 to above 200 cells/microliter 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 recognized.[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; epidemiologic, historic, 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 rifampin for 4 months, or daily isoniazid plus rifampin 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/microliter 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/microliter 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. 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 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/microliter.[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] Serologic testing for coccidioidomycosis is advised in people living with HIV 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 people living with HIV currently living in endemic areas who have a CD4 <250 cells/microliter.[1] Primary prophylaxis with fluconazole is indicated for asymptomatic people living with HIV 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 count is ≥250 cells/microliter.[1] Individuals 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]
Histoplasmosis
For people living with HIV, with CD4 count <150 cells/microliter, 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/microliter for 6 months.[1] If the CD4 count falls to <150 cells/microliter, prophylaxis should be restarted.[1]
The table that follows summarizes recommendations for primary prevention of HIV-related opportunistic infections taken from National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association, and Infectious Diseases Society of America guidance on adult and adolescent opportunistic infections.[1]
Note that an individual patient may fall into more than one group, and so interventions might be additive; please review all population and subpopulation groups to assess all that apply.
Adults living with HIV
All
Intervention
Effective antiretroviral therapy (ART), education on early manifestations of disease and prevention of opportunistic infections
Durable viral suppression eliminates most but not all opportunistic infections.
For information on recommended ART regimens, see HIV in adults.
For the prevention of exposure to toxoplasmosis, advise people living with HIV, especially those with CD4 counts <200 cells/microliter:
not to eat raw or undercooked meat (including lamb, beef, pork or venison)
not to eat raw shellfish (including oysters, clams and mussels)
to wash their hands after contact with raw meat and after gardening or other contact with soil
to wash fruits and vegetables well before eating them raw, and
to avoid direct contact with cat feces.
Advise people living with HIV that cytomegalovirus (CMV) is shed in semen, cervical secretions and saliva. Advise them to use latex condoms during sexual contact to reduce the risk of exposure to CMV, as well as other sexually transmitted pathogens.
Advise people living with HIV who are living in or visiting areas in which Coccidioides spp. are endemic to avoid extensive exposure to disturbed native soil, such as at building excavation sites, and to stay inside during dust storms. No evidence indicates that gardening in cultivated soil in the coccidioidal endemic region increases the risk of acquiring coccidioidomycosis.
Consider advising people that limited epidemiologic evidence suggests that exposure to dried bird droppings, including those from chickens and pet birds, may increase the risk of infection with Cryptococcus.
Goal
Ongoing viral suppression; prevention or reduction of HIV-related opportunistic infections
With latent tuberculosis (TB), or a close contact of person with infectious TB
Intervention
Treatment for latent TB infection
Latent TB: Treat all people living with HIV for latent TB infection who have all of the following:
A positive screening test for latent TB infection (e.g., tuberculin skin test [TST] or interferon gamma release assay [IGRA] regardless of Bacillus Calmette-Guérin (BCG) vaccination status.
No evidence of active TB.
No history of treatment for active or latent TB.
Close contacts of infectious TB: Treat for latent TB all people living with HIV who are a close contact of a person with infectious TB (including someone who has shared air space, such as in a household or close congregate setting, with a person with active pulmonary TB). Treatment is recommended regardless of screening test result and CD4 count for this group.
For all people living with HIV requiring treatment for latent TB, selection of the treatment regimen is individualized, and may depend on the potential for drug interactions, toxicity concerns, as well as medication availability and/or cost.
Seek expert and public health authority advice for people exposed to drug-resistant TB.
Treatment of latent TB and ART act independently to decrease the risk of active TB; therefore, use both interventions for people with HIV and latent TB; deferring ART until after treatment for latent TB is not recommended.
Goal
Prevention of active TB
The goal is successful completion of the treatment regimen for latent TB.
People with HIV who have been treated successfully for latent TB do not require repeat testing with TST or IGRA; a previously positive test result generally will not revert to negative.
With a new positive serological immunoglobulin M (IgM) and/or immunoglobulin G (IgG) test for Coccidioides, and CD4 count <250 cells/microliter, and no evidence of active coccidioidomycosis
Intervention
Prophylaxis against coccidioidomycosis
Offer primary prophylaxis with fluconazole for asymptomatic people living with HIV who have a positive serologic test for coccidioidomycosis with a CD4 count <250 cells/microliter.
Goal
Prevention of active coccidioidomycosis infection
Continue prophylaxis with fluconazole until:
CD4 count ≥250 cells/microliter, and
the patient achieves virologic suppression.
Following treatment discontinuation, close follow up to assess for signs and symptoms of coccidioidomycosis is recommended.
With CD4 count <100 cells/microliter regardless of plasma HIV levels, or with CD4 count between 100 and 200 cells/microliter with plasma HIV ribonucleic acid (RNA) levels above detection limits
Intervention
Prophylaxis against Pneumocystis jirovecii pneumonia (PCP)
Offer prophylaxis against PCP to all adults with HIV with a CD4 count <100 cells/microliter regardless of plasma HIV levels, or with a CD4 count between 100 and 200 cells/microliter with plasma HIV ribonucleic acid (RNA) levels above detection limits.
Trimethoprim/sulfamethoxazole (TMP/SMX) is the recommended prophylactic agent for PCP.
Alternatives include dapsone, dapsone plus pyrimethamine plus leucovorin, aerosolized pentamidine, intravenous pentamidine, and atovaquone.
People who are receiving pyrimethamine/sulfadiazine for treatment or suppression of toxoplasmosis do not require additional prophylaxis for PCP.
Goal
Prevention of PCP
Continue prophylaxis against PCP pneumonia indefinitely unless CD4 increases to >200 cells/microliter for 3 months or longer.
Reintroduce prophylaxis if the patient’s CD4 count decreases to <200 cells/microliter.
Seropositive for Toxoplasmosis gondii, and CD4 count <100 cells/microliter
Intervention
Prophylaxis against Toxoplasmosis gondii
Offer prophylaxis against Toxoplasmosis gondii to Toxoplasma-seropositive patients with CD4 counts <100 cells/microliter.
Trimethoprim/sulfamethoxazole (TMP/SMX) is the preferred prophylactic agent.
Alternatives include dapsone plus pyrimethamine plus leucovorin; or atovaquone.
Goal
Prevention of toxoplasmosis
Continue indefinitely unless CD4 increases to >200 cells/microliter for 3 months or longer.
With positive screening serum cryptococcal antigen test and CD4 count <100 cells/microliter
Intervention
Prophylaxis against cryptococcal meningitis
Antifungal prophylaxis to reduce the frequency of primary cryptococcal disease is recommended for:
patients with HIV who have CD4 counts <100 cells/microliter, and
a positive serum cryptococcal antigen (CrAg) test.
In the US, prophylaxis against cryptococcal meningitis is not recommended for those without a positive serum CrAg because of the relative infrequency of cryptococcal disease, lack of survival benefit associated with prophylaxis, possibility of drug-drug interactions, and potential development of antifungal drug resistance.
Goal
Prevention of cryptococcal meningitis
Not on fully suppressive antiretroviral therapy (ART), and CD4 count <50 cells/microliter
Intervention
Prophylaxis against Mycobacterium avium complex (MAC)
Offer prophylaxis against disseminated MAC disease to people with HIV who have a CD4 count <50 cells/microliter, and who are not receiving ART or who remain viremic on ART, or who have no options for a fully suppressive ART regimen.
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.
Rule out disseminated MAC disease before starting prophylaxis, and active TB infection before starting rifabutin.
Goal
Prevention of MAC
Continue prophylaxis indefinitely in the absence of ART.
Discontinue primary MAC prophylaxis in those receiving a fully suppressive ART regimen.
With a CD4 count <150 cells/mm³, with occupational histoplasmosis exposure or living in areas with an incidence of Histoplasma >10 cases per 100 patient-years
Intervention
Prophylaxis against histoplasmosis
Prophylaxis with itraconazole is recommended.
Goal
Prevention of histoplasmosis
Continue prophylaxis until all of the following occur:
Stable ART
CD4 count ≥150 cells/mm³ for at least 6 months
Undetectable HIV-1 viral load
Restart prophylaxis if the CD4 count falls to <150 cells/mm³.
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][291]
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 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 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/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.[292]
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/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 individuals 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][293]
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.[294]
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/microliter 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/microliter 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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