Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

Mycobacterium tuberculosis infection

1st line – intensive phase: directly observed therapy

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ACUTE
|
Mycobacterium tuberculosis infection
|
drug-susceptible
1st line – 

intensive phase: directly observed therapy

Early diagnosis and treatment of tuberculosis (TB) are critical and should follow the general principles developed for TB treatment in people not living with HIV. Directly observed therapy (DOT) is strongly encouraged to provide effective therapy, prevent resistance, and allow cure with a relatively short course of treatment (6-9 months). The treatment plan should be based on completion of the total number of recommended doses ingested rather than the duration of treatment administration.

Treatment of TB is provided in two phases: an initial intensive phase followed immediately by a continuation phase. Empiric antituberculous drug therapy should be started while susceptibility tests are pending. Potential drug-drug interactions should be carefully assessed and antiretroviral treatment (ART) and TB regimens should be adjusted accordingly.

Intensive phase: isoniazid, rifampin or rifabutin, pyrazinamide, and ethambutol in combination are given daily (5-7 days per week) for 2 months (8 weeks).[1][217][218]​ Ethambutol should be stopped if isolate is sensitive to isoniazid, rifampin, or rifabutin.

All people living with HIV treated with isoniazid should receive pyridoxine supplementation to help prevent isoniazid-associated neuropathy.[1]

Rifabutin has less effect on the serum concentrations of protease inhibitors than rifampin. Individuals on protease-inhibitor-based ART regimens should receive rifabutin instead of rifampin in their TB-treatment regimen. Specialist consultation is recommended when considering use of rifabutin while the individual is on a protease inhibitor.

For people living with HIV who are ART-naïve and diagnosed with active TB, US guidelines recommend that ART should be started within 2 weeks after initiation of anti-TB treatment when the CD4 count is <50 cells/microliter and within 8 weeks of starting anti-TB treatment in individuals with higher CD4 counts.[1][217]​​​ Guidelines also recommend that in those with TB involving the central nervous system, initiation of ART should be delayed until 8 weeks of TB treatment has been completed, regardless of CD4 count.[1][217]​​​ World Health Organization guidelines recommend that ART be started as soon as possible within two weeks of starting TB treatment, regardless of CD4 count, unless the individual has TB meningitis (when ART is delayed for 4-8 weeks).[218] If TB occurs in individuals already on ART, anti-TB treatment should be started immediately and ART might need to be modified to reduce the risk for drug interactions while maintaining virologic suppression.[1]

Consultation with an experienced specialist should be considered when starting TB treatment in people living with HIV taking antiretrovirals, as the drug interactions are complex and important.

Primary options

isoniazid: 5 mg/kg orally once daily, maximum 300 mg/day

-- AND --

rifampin: 10 mg/kg orally once daily, maximum 600 mg/day

or

rifabutin: 5 mg/kg orally once daily, maximum 300 mg/day

-- AND --

pyrazinamide: body weight 40-55 kg: 1000 mg orally once daily; body weight 56-75 kg: 1500 mg orally once daily; body weight ≥76 kg: 2000 mg orally once daily

-- AND --

ethambutol: body weight 40-55 kg: 800 mg orally once daily; body weight 56-75 kg: 1200 mg orally once daily; body weight ≥76 kg: 1600 mg orally once daily

-- AND --

pyridoxine (vitamin B6): 25-50 mg orally once daily

Plus – consider corticosteroid

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ACUTE
|
Mycobacterium tuberculosis infection
|
drug-susceptible
Plus – 

consider corticosteroid

Treatment recommended for ALL patients in selected patient group

Adjunctive corticosteroid therapy should be considered in people living with HIV with tuberculosis (TB) involving the central nervous system, since corticosteroids given concomitantly with antituberculosis therapy have been shown to improve clinical outcomes and mortality in persons with TB meningitis.[1][220]

Primary options

dexamethasone: consult specialist for guidance on dose

Plus – continuation phase: directly observed therapy

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ACUTE
|
Mycobacterium tuberculosis infection
|
drug-susceptible
Plus – 

continuation phase: directly observed therapy

Treatment recommended for ALL patients in selected patient group

The optimal duration of treatment is not known. For the majority of individuals, 4 months of continuation-phase therapy is probably adequate, but prolonged therapy is recommended for some.[1][217][218]​ A total duration of therapy of 6 months is recommended for drug-susceptible pulmonary tuberculosis (TB), and for extrapulmonary TB other than disseminated extrapulmonary TB or TB of the central nervous system (CNS) or bone/joint. A total of 9 months is recommended for pulmonary TB with positive culture at 2 months of treatment, severe cavitary disease or disseminated TB, 9-12 months for extrapulmonary TB with CNS involvement, and 6-9 months for extrapulmonary TB with bone or joint involvement.[1][217][218]

All people living with HIV treated with isoniazid should receive pyridoxine supplementation to help prevent isoniazid-associated neuropathy.[1]

For individuals with a low risk of exposure and transmission of TB infection, chronic suppressive treatment after successful completion of initiation and continuation phases of treatment for latent or active TB infection is not necessary.

The regimen is given 5-7 times per week by directly observed therapy.

Primary options

isoniazid: 5 mg/kg orally once daily, maximum 300 mg/day

-- AND --

rifampin: 10 mg/kg orally once daily, maximum 600 mg/day

or

rifabutin: 5 mg/kg orally once daily, maximum 300 mg

-- AND --

pyridoxine (vitamin B6): 25-50 mg orally once daily

2nd line – intensive phase: directly observed therapy (4-month regimen)

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ACUTE
|
Mycobacterium tuberculosis infection
|
drug-susceptible
2nd line – 

intensive phase: directly observed therapy (4-month regimen)

An alternative treatment option for active pulmonary tuberculosis (TB) is a 4-month regimen of daily isoniazid, rifapentine, moxifloxacin, and pyrazinamide. However, this alternative regimen is only recommended in individuals receiving efavirenz-based antiretroviral therapy who have CD4 counts ≥100 cells/microliter and no other known drug-drug interactions.[1][218]

An international, randomized, controlled, open-label phase 3 noninferiority clinical trial found that a 4-month daily treatment regimen containing high-dose (optimized) rifapentine with moxifloxacin is as effective as the standard daily 6-month regimen in the treatment of pulmonary TB.[219]

People living with HIV treated with isoniazid should receive pyridoxine supplementation to help prevent isoniazid-associated neuropathy.[1]

Systemic fluoroquinolone antibiotics, such as moxifloxacin, are a key part of some TB treatment regimens, but it is important to note that they may cause serious, disabling, and potentially long-lasting or irreversible adverse events. This includes, but is not limited to: tendinopathy/tendon rupture; peripheral neuropathy; arthropathy/arthralgia; aortic aneurysm and dissection; heart valve regurgitation; dysglycemia; and central nervous system effects including seizures, depression, psychosis, and suicidal thoughts and behavior.[225]​ Prescribing restrictions apply to the use of fluoroquinolones, and these restrictions may vary between countries. In general, fluoroquinolones should be restricted for use in serious, life-threatening bacterial infections only. Some regulatory agencies may also recommend that they must only be used in situations where other antibiotics, that are commonly recommended for the infection, are inappropriate (e.g., resistance, contraindications, treatment failure, unavailability). Consult your local guidelines and drug information source for more information on suitability, contraindications, and precautions.

Consult with an experienced specialist should be considered when starting TB treatment in people living with HIV taking antiretrovirals, as the drug interactions are complex and important.

Primary options

isoniazid: 5 mg/kg orally once daily, maximum 300 mg/day

and

rifapentine: body weight ≥40 kg: 1200 mg orally once daily

and

moxifloxacin: body weight ≥40 kg: 400 mg orally once daily

and

pyrazinamide: body weight 40-55 kg: 1000 mg orally once daily; body weight 56-75 kg: 1500 mg orally once daily; body weight ≥76 kg: 2000 mg orally once daily

and

pyridoxine (vitamin B6): 25-50 mg orally once daily

Plus – consider corticosteroid

Back
ACUTE
|
Mycobacterium tuberculosis infection
|
drug-susceptible
Plus – 

consider corticosteroid

Treatment recommended for ALL patients in selected patient group

Adjunctive corticosteroid therapy should be considered in people living with HIV with tuberculossi (TB) involving the central nervous system, since corticosteroids given concomitantly with antituberculosis therapy have been shown to improve clinical outcomes and mortality in persons with TB meningitis.[1][220]

Primary options

dexamethasone: consult specialist for guidance on dose

Plus – continuation phase: directly observed therapy (4-month regimen)

Back
ACUTE
|
Mycobacterium tuberculosis infection
|
drug-susceptible
Plus – 

continuation phase: directly observed therapy (4-month regimen)

Treatment recommended for ALL patients in selected patient group

The continuation phase for the alternative regimen consists of isoniazid, rifapentine, and moxifloxacin for 9 weeks. The alternative regimen is only recommended in individuals receiving efavirenz-based antiretroviral therapy who have CD4 counts ≥100 cells/microliter and no other known drug-drug interactions.[1][218]

All people living with HIV treated with isoniazid should receive pyridoxine supplementation to help prevent isoniazid-associated neuropathy.[1]

Primary options

isoniazid: 5 mg/kg orally once daily, maximum 300 mg/day

and

rifapentine: body weight ≥40 kg: 1200 mg orally once daily

and

moxifloxacin: body weight ≥40 kg: 400 mg orally once daily

and

pyridoxine (vitamin B6): 25-50 mg orally once daily

1st line – antituberculous treatment: directly observed therapy

Back
ACUTE
|
Mycobacterium tuberculosis infection
|
isoniazid-resistant
1st line – 

antituberculous treatment: directly observed therapy

Individuals with isoniazid resistance should receive a regimen consisting of rifabutin or rifampin, pyrazinamide, and ethambutol, with a fluoroquinolone (moxifloxacin or levofloxacin) for 6 months.[1][221]

Systemic fluoroquinolone antibiotics are a key part of some tuberculosis treatment regimens, but it is important to note that they may cause serious, disabling, and potentially long-lasting or irreversible adverse events. This includes, but is not limited to: tendinopathy/tendon rupture; peripheral neuropathy; arthropathy/arthralgia; aortic aneurysm and dissection; heart valve regurgitation; dysglycemia; and central nervous system effects including seizures, depression, psychosis, and suicidal thoughts and behavior.[225]​ Prescribing restrictions apply to the use of fluoroquinolones, and these restrictions may vary between countries. In general, fluoroquinolones should be restricted for use in serious, life-threatening bacterial infections only. Some regulatory agencies may also recommend that they must only be used in situations where other antibiotics, that are commonly recommended for the infection, are inappropriate (e.g., resistance, contraindications, treatment failure, unavailability). Consult your local guidelines and drug information source for more information on suitability, contraindications, and precautions.

Primary options

rifampin: 10 mg/kg orally once daily, maximum 600 mg/day

or

rifabutin: 5 mg/kg orally once daily, maximum 300 mg/day

-- AND --

pyrazinamide: body weight 40-55 kg: 1000 mg orally once daily; body weight 56-75 kg: 1500 mg orally once daily; body weight ≥76 kg: 2000 mg orally once daily

-- AND --

ethambutol: body weight 40-55 kg: 800 mg orally once daily; body weight 56-75 kg: 1200 mg orally once daily; body weight ≥76 kg: 1600 mg orally once daily

-- AND --

moxifloxacin: 400 mg orally/intravenously once daily

or

levofloxacin: 500-750 mg orally/intravenously once daily

1st line – consultation and individualized therapy

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ACUTE
|
Mycobacterium tuberculosis infection
|
multidrug-resistant
1st line – 

consultation and individualized therapy

For tuberculosis (TB) resistant to other TB drugs, therapy depends on individual resistance pattern, and consultation with an experienced specialist is needed for multidrug resistant tuberculosis (MDR-TB). A history of treatment for TB has been the only predictor for MDR-TB in a cohort of people living with HIV and TB.[222] Individuals with MDR-TB are at high risk for treatment failure and relapse. Treatment regimens for MDR-TB should be individualized.[1][221]

disseminated M avium complex

1st line – combination antimycobacterial therapy

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ACUTE
|
disseminated M avium complex
|
without advanced immunosuppression
1st line – 

combination antimycobacterial therapy

All isolates should be tested for drug susceptibility, since rates of drug resistance are high.[226]​ Treatment should include a macrolide (either azithromycin or clarithromycin) plus ethambutol.[1][228] 

It is imperative that people living with HIV with disseminated Mycobacterium avium complex (MAC) receive suppressive antiretroviral treatment (ART), since concurrent treatment with ART and drugs for the treatment of MAC are associated with improved outcomes and lower rates of relapse. Since disseminated MAC may lead to impaired gastrointestinal absorption, monitoring therapeutic drug levels may be considered.[227]

For individuals already on ART, close monitoring for any drug interactions between ART and antimycobacterial drugs is important.

ART should be initiated as soon as possible after the diagnosis of disseminated MAC and preferably at the same time, if the individual is not already on ART.[1]

Lifelong secondary prophylaxis is recommended for individuals with disseminated MAC infection, unless immune reconstitution occurs as a result of antiretroviral treatment.[230] The chronic maintenance therapy (secondary prophylaxis) is the same as the initial treatment regimens.

Treatment should be continued for at least 12 months; maintenance therapy can be discontinued after this time if the individual has no MAC signs or symptoms and has a sustained (>6 months) CD4 count >100 cells/microliter in response to ART.[1] Chronic maintenance therapy/secondary prophylaxis may be reintroduced if CD4 count decreases to levels consistently <100 cells/microliter and a fully suppressive ART regimen is not possible.[1]

Primary options

azithromycin: 500-600 mg orally once daily

or

clarithromycin: 500 mg (immediate-release) orally twice daily

-- AND --

ethambutol: 15 mg/kg orally once daily

Plus – addition of third or fourth drug to combination regimen

Back
ACUTE
|
disseminated M avium complex
|
with advanced immunosuppression, high mycobacterial loads, or the absence of effective ART
Plus – 

addition of third or fourth drug to combination regimen

Treatment recommended for ALL patients in selected patient group

A third or fourth drug may be added to the initial combination regimen in individuals with advanced immunosuppression (CD4 count <50 cells/microliter) or high mycobacterial load, or in the absence of effective antiretroviral therapy.

Options for a third or fourth drug may include rifabutin, a fluoroquinolone (e.g., levofloxacin, moxifloxacin), or an injectable aminoglycoside (e.g., amikacin, streptomycin).[1][228][229]

Systemic fluoroquinolone antibiotics may cause serious, disabling, and potentially long-lasting or irreversible adverse events. This includes, but is not limited to: tendinopathy/tendon rupture; peripheral neuropathy; arthropathy/arthralgia; aortic aneurysm and dissection; heart valve regurgitation; dysglycemia; and central nervous system effects including seizures, depression, psychosis, and suicidal thoughts and behavior.[225]​ Prescribing restrictions apply to the use of fluoroquinolones, and these restrictions may vary between countries. In general, fluoroquinolones should be restricted for use in serious, life-threatening bacterial infections only. Some regulatory agencies may also recommend that they must only be used in situations where other antibiotics, that are commonly recommended for the infection, are inappropriate (e.g., resistance, contraindications, treatment failure, unavailability). Consult your local guidelines and drug information source for more information on suitability, contraindications, and precautions.

Primary options

rifabutin: 300 mg orally once daily

OR

amikacin: 10-15 mg/kg intravenously every 24 hours

OR

streptomycin: 1 g intravenously/intramuscularly every 24 hours

OR

levofloxacin: 500 mg orally once daily

OR

moxifloxacin: 400 mg orally once daily

Pneumocystis jirovecii pneumonia

1st line – initial antimicrobial therapy

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ACUTE
|
Pneumocystis jirovecii pneumonia
|
mild-to-moderate disease
1st line – 

initial antimicrobial therapy

Mild-to-moderate disease is defined as arterial blood gas room air pO₂ ≥70 mmHg or an alveolar-arterial (A-a) gradient ≤35 mmHg.

Trimethoprim/sulfamethoxazole is the treatment of choice and should be given orally to those with mild disease who do not have gastrointestinal dysfunction; it should be given intravenously for individuals who are unable to receive or absorb drugs.[1][231]​​ Oral outpatient therapy with trimethoprim/sulfamethoxazole is highly effective for stable individuals with mild-to-moderate disease.[1] Individuals who develop P jirovecii pneumonia (PCP) while on trimethoprim/sulfamethoxazole for prophylaxis are usually effectively treated with standard doses of trimethoprim/sulfamethoxazole.

Alternative treatments include dapsone plus trimethoprim, primaquine plus clindamycin, and atovaquone suspension.[1]

Duration of therapy is 21 days.[1]

Antiretroviral treatment should be initiated in individuals not already prescribed it within 2 weeks of diagnosis of PCP when possible.[1]

Primary options

sulfamethoxazole/trimethoprim: 15-20 mg/kg/day orally/intravenously given in 3-4 divided doses; or 320 mg orally three times daily

More

Secondary options

dapsone: 100 mg orally once daily

and

trimethoprim: 5 mg/kg orally three times daily

OR

primaquine phosphate: 30 mg orally once daily

More

and

clindamycin: 450 mg orally four times daily; or 600 mg orally three times daily

OR

atovaquone: 750 mg orally twice daily

Plus – maintenance prophylaxis

Back
ACUTE
|
Pneumocystis jirovecii pneumonia
|
mild-to-moderate disease
Plus – 

maintenance prophylaxis

Treatment recommended for ALL patients in selected patient group

Lifelong secondary prophylaxis should be considered for all individuals who have a history of P jirovecii pneumonia (PCP) unless immune reconstitution occurs as a result of antiretroviral treatment.[1] Secondary prophylaxis should be restarted if CD4 count decreases to <100 cells/microliter regardless of HIV RNA, or CD4 count 100-200 cells/microliter and HIV RNA above detection limit of the assay used.[1]

Secondary prophylaxis options are based around those regimens used to treat initial disease.

These include trimethoprim/sulfamethoxazole, dapsone, dapsone plus pyrimethamine and leucovorin, atovaquone, atovaquone plus pyrimethamine and leucovorin, and aerosolized pentamidine.

Primary options

sulfamethoxazole/trimethoprim: 80-160 mg orally once daily

More

Secondary options

sulfamethoxazole/trimethoprim: 160 mg orally three times weekly

More

OR

dapsone: 100 mg orally once daily; or 50 mg orally twice daily

OR

dapsone: 50 mg orally once daily

and

pyrimethamine: 50 mg orally once weekly

and

leucovorin: 25 mg orally once weekly

OR

dapsone: 200 mg orally once weekly

and

pyrimethamine: 75 mg orally once weekly

and

leucovorin: 25 mg orally once weekly

OR

pentamidine inhaled: 300 mg nebulized once monthly

OR

atovaquone: 1500 mg orally once daily

Tertiary options

atovaquone: 1500 mg orally once daily

and

pyrimethamine: 25 mg orally once daily

and

leucovorin: 10 mg orally once daily

1st line – initial antimicrobial therapy

Back
ACUTE
|
Pneumocystis jirovecii pneumonia
|
moderate-to-severe disease
1st line – 

initial antimicrobial therapy

Moderate-to-severe disease is defined as pO₂ <70 mmHg or arterial-alveolar O₂ gradient >35 mmHg on room air. For individuals with respiratory compromise, intensive care unit admission and ventilator support should be offered when appropriate.[232]

Trimethoprim/sulfamethoxazole is the treatment of choice.[1] Intravenous treatment is initiated, switching to oral therapy after clinical improvement.[1]​ Individuals generally improve clinically within 4-8 days.[233]

Alternative regimens may be considered if there is no clinical improvement after 4-5 days or if the individual is intolerant of trimethoprim/sulfamethoxazole. These include intravenous pentamidine, or clindamycin plus primaquine.[1]

While it has been shown to be effective, pentamidine is associated with potentially life-threatening toxicities, including severe renal dysfunction and QT interval prolongation.[234]

Duration of therapy is 21 days.[1]

Antiretroviral treatment should be initiated in individuals not already on it within 2 weeks of diagnosis of P jirovecii pneumonia where possible.[1]

Primary options

sulfamethoxazole/trimethoprim: 15-20 mg/kg/day intravenously given in divided doses every 6-8 hours, may switch to oral dosing after clinical improvement

More

Secondary options

pentamidine: 4 mg/kg intravenously once daily, can reduce dose to 3 mg/kg once daily if necessary due to toxicities

OR

primaquine phosphate: 30 mg orally once daily

More

and

clindamycin: 600 mg intravenously every 6 hours, or 900 mg intravenously every 8 hours; or 450 mg orally four times daily, or 600 mg orally three times daily

Plus – corticosteroid

Back
ACUTE
|
Pneumocystis jirovecii pneumonia
|
moderate-to-severe disease
Plus – 

corticosteroid

Treatment recommended for ALL patients in selected patient group

Corticosteroids should be given to all individuals with moderate-to-severe disease, i.e., those with a partial pressure of oxygen of <70 mmHg on room air or an A-a oxygen gradient of >35 mmHg. If an arterial blood glass is not obtained, an oxygen saturation of <92% on room air can be used as a surrogate marker for moderate-to-severe disease.[1][235]​​​ Corticosteroids should also be considered for individuals who develop worsening respiratory symptoms after initiation of treatment.

Intravenous methylprednisolone can be given as 75% of prednisone dose.[1]

Primary options

prednisone: 40 mg orally twice daily for 5 days, followed by 40 mg once daily for 5 days, followed by 20 mg once daily for 11 days

OR

methylprednisolone sodium succinate: 30 mg intravenously twice daily for 5 days, then 30 mg once daily for 5 days, then 15 mg once daily for 11 days

Plus – maintenance prophylaxis

Back
ACUTE
|
Pneumocystis jirovecii pneumonia
|
moderate-to-severe disease
Plus – 

maintenance prophylaxis

Treatment recommended for ALL patients in selected patient group

Lifelong secondary prophylaxis should be considered for all the individuals who have a history of P jirovecii pneumonia unless immune reconstitution occurs as a result of antiretroviral treatment.[1] Secondary prophylaxis should be restarted if CD4 count decreases to <100 cells/microliter regardless of HIV RNA, or CD4 count 100-200 cells/microliter and HIV RNA above detection limit of the assay used.[1]

Secondary prophylaxis options are based around those regimens used to treat initial disease.

These include trimethoprim/sulfamethoxazole, dapsone, dapsone plus pyrimethamine and leucovorin, atovaquone, atovaquone plus pyrimethamine and leucovorin, and aerosolized pentamidine.

Primary options

sulfamethoxazole/trimethoprim: 80-160 mg orally once daily

More

Secondary options

sulfamethoxazole/trimethoprim: 160 mg orally three times weekly

More

OR

dapsone: 100 mg orally once daily; or 50 mg orally twice daily

OR

dapsone: 50 mg orally once daily

and

pyrimethamine: 50 mg orally once weekly

and

leucovorin: 25 mg orally once weekly

OR

dapsone: 200 mg orally once weekly

and

pyrimethamine: 75 mg orally once weekly

and

leucovorin: 25 mg orally once weekly

OR

pentamidine inhaled: 300 mg nebulized once monthly

OR

atovaquone: 1500 mg orally once daily

Tertiary options

atovaquone: 1500 mg orally once daily

and

pyrimethamine: 25 mg orally once daily

and

leucovorin: 10 mg orally once daily

Toxoplasma gondii infection encephalitis

1st line – initial anti-Toxoplasma regimen

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ACUTE
|
Toxoplasma gondii infection encephalitis
1st line – 

initial anti-Toxoplasma regimen

Initial therapy should consist of the combination of pyrimethamine plus sulfadiazine plus leucovorin, all administered orally.[1] Leucovorin is used to protect against the hematologic toxicities associated with pyrimethamine.[237]

Although this is the preferred regimen, the high cost and limited availability have become a major barrier to its use in the US. Trimethoprim/sulfamethoxazole has become an alternative, and can be given orally or intravenously.[238] While the clinical trial data in support of trimethoprim/sulfamethoxazole are not as robust, several trials have demonstrated that it has comparable efficacy and safety.[238][239]​​​ For individuals with a sulfa allergy history, desensitization should be considered.[1]​​

Other alternative regimens include pyrimethamine plus leucovorin plus either clindamycin or atovaquone, atovaquone plus sulfadiazine, or atovaquone alone.[1]

Clinical and radiographic improvement should be expected within 10-21 days of therapy.[122]​​​ Treatment should be continued for at least 6 weeks after resolution of symptoms.

Individuals with T gondii infection encephalitis should be routinely monitored for adverse events and clinical and radiologic improvement. Changes in the antibody titers are not useful for monitoring responses to therapy.

Individuals who show clinical or radiographic deterioration during the first week despite adequate therapy, or who lack clinical improvement within 2 weeks, should undergo brain biopsy. A switch to an alternative regimen should be considered if there is histopathologic evidence of T gondii infection encephalitis from the brain biopsy.[1]

Primary options

pyrimethamine: body weight <60 kg: 200 mg orally as a single dose, followed by 50 mg once daily; body weight ≥60 kg: 200 mg orally as a single dose, followed by 75 mg once daily

and

sulfadiazine: body weight <60 kg: 1000 mg orally four times daily; body weight ≥60 kg: 1500 mg orally four times daily

and

leucovorin: 10-25 mg orally once daily

More

OR

sulfamethoxazole/trimethoprim: 5 mg/kg orally/intravenously twice daily

More

Secondary options

pyrimethamine: body weight <60 kg: 200 mg orally as a single dose, followed by 50 mg once daily; body weight ≥60 kg: 200 mg orally as a single dose, followed by 75 mg once daily

-- AND --

clindamycin: 600 mg orally/intravenously four times daily

or

atovaquone: 1500 mg orally twice daily

-- AND --

leucovorin: 10-25 mg orally once daily

More

OR

atovaquone: 1500 mg orally twice daily

and

sulfadiazine: body weight <60 kg: 1000 mg orally four times daily; body weight ≥60 kg: 1500 mg orally four times daily

OR

atovaquone: 1500 mg orally twice daily

Consider – corticosteroids and anticonvulsants

Back
ACUTE
|
Toxoplasma gondii infection encephalitis
Consider – 

corticosteroids and anticonvulsants

Treatment recommended for SOME patients in selected patient group

Adjunctive corticosteroids are not routinely recommended but should be considered if there are clinical signs of increased intracranial pressure or evidence of mass effect due to focal lesions or edema.[1]

Anticonvulsants should be administered to individuals with T gondii infection encephalitis who have a history of seizures, but should not be administered as prophylactics to all individuals.[1]

Plus – maintenance prophylaxis

Back
ACUTE
|
Toxoplasma gondii infection encephalitis
Plus – 

maintenance prophylaxis

Treatment recommended for ALL patients in selected patient group

Individuals who have completed initial therapy for toxoplasmic encephalitis should be given suppressive therapy with maintenance prophylaxis.

The recommended regimen for secondary prophylaxis is pyrimethamine plus sulfadiazine plus leucovorin.

Alternative regimens include clindamycin plus pyrimethamine plus leucovorin, trimethoprim/sulfamethoxazole, atovaquone plus sulfadiazine, or atovaquone with or without pyrimethamine and leucovorin.[1]

Chronic maintenance may be discontinued in individuals who have successfully completed initial therapy for toxoplasmic encephalitis, remain asymptomatic, and have an increase in their CD4 counts to >200 cells/microliter after antiretroviral treatment sustained for more than 6 months.[1] Secondary prophylaxis should be reintroduced if the CD4 count decreases to <200 cells/microliter.

Primary options

pyrimethamine: 25-50 mg orally once daily

and

sulfadiazine: 2-4 g/day orally given in 2-4 divided doses

and

leucovorin: 10-25 mg orally once daily

Secondary options

pyrimethamine: 25-50 mg orally once daily

and

clindamycin: 600 mg orally three times daily

and

leucovorin: 10-25 mg orally once daily

OR

sulfamethoxazole/trimethoprim: 160 mg orally once or twice daily

More

OR

atovaquone: 750-1500 mg orally twice daily

and

sulfadiazine: 2-4 g/day orally given in 2-4 divided doses

OR

atovaquone: 750-1500 mg orally twice daily

and

pyrimethamine: 25 mg orally once daily

and

leucovorin: 10 mg orally once daily

OR

atovaquone: 750-1500 mg orally twice daily

cryptococcal meningitis

1st line – antifungal induction therapy

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ACUTE
|
cryptococcal meningitis
1st line – 

antifungal induction therapy

The preferred regimen recommended by US guidelines for induction therapy is at least 2 weeks of intravenous liposomal amphotericin-B plus oral flucytosine.[1] Lipid or liposomal formulations of amphotericin-B are preferred to amphotericin-B deoxycholate, where available, because they are effective for cryptococcosis and have lower toxicity.[1]​ Amphotericin-B deoxycholate is associated with renal impairment, renal tubular acidosis, hypokalemia, hypomagnesemia, and anemia.[240]​ However, amphotericin-B deoxycholate can be used as an alternative formulation if risk of renal dysfunction is low or if cost is prohibitive.[1]​

Alternative induction regimens recommended by the US guidelines are 2 weeks of intravenous amphotericin-B lipid complex plus oral flucytosine, or 1 week of amphotericin-B deoxycholate plus oral flucytosine followed by 1 week of oral fluconazole.[1]

The World Health Organization (WHO) recommends an induction regimen that consists of a single high dose of liposomal amphotericin-B combined plus 14 days of flucytosine and fluconazole, especially in resource-limited settings.[76] An alternative regimen recommended by WHO (where liposomal amphotericin-B is not available) is 1 week of amphotericin-B deoxycholate and flucytosine followed by 1 week of fluconazole.[76]

The addition of flucytosine during acute treatment is associated with more rapid sterilization of the cerebrospinal fluid, fewer relapses, and improved survival.[1][241]​​[242]​​​ Flucytosine is contraindicated in individuals with known complete dihydropyrimidine dehydrogenase deficiency due to the risk of life-threatening toxicity.[243][244]

Renal function should be monitored if >2-week course of amphotericin-B and flucytosine with appropriate dose adjustment (monitor serum flucytosine 2 hours postdose after 3-5 doses have been administered, optimal levels: 25-100 mg/mL). If flucytosine levels are not available, frequent (i.e., at least twice weekly) blood counts can be performed to detect cytopenia. Hepatotoxicity and gastrointestinal toxicities should also be monitored in patients receiving flucytosine.[1]

The optimal time to begin antiretroviral therapy (ART) in individuals with cryptococcal meningitis remains unclear.[1] Initiation of ART is generally delayed for 4-6 weeks after starting antifungal therapy; however, the exact timing should be individualized, based on circumstances and local experience.[1][76]​ Individuals should be monitored for immune reconstitution inflammatory syndrome. Caution should be applied when using azole antifungal drugs together with antiretroviral drugs as there is a risk for significant drug interactions through the CYP450 enzyme system.[1]

Primary options

amphotericin B liposomal: 3-4 mg/kg intravenously once daily for 2 weeks

and

flucytosine: 25 mg/kg orally four times daily for 2 weeks

OR

amphotericin B liposomal: 10 mg/kg intravenously as a single dose

More

-- AND --

flucytosine: 25 mg/kg orally four times daily for 2 weeks

and

fluconazole: 1200 mg orally once daily for 2 weeks

Secondary options

amphotericin B lipid complex: 5 mg/kg intravenously once daily for 2 weeks

and

flucytosine: 25 mg/kg orally four times daily for 2 weeks

OR

amphotericin B deoxycholate: 1 mg/kg intravenously once daily for 1 week

and

flucytosine: 25 mg/kg orally four times daily for 1 week

and

fluconazole: 1200 mg orally once daily for 1 week (after 1-week course of amphotericin B deoxycholate and flucytosine)

Tertiary options

amphotericin B deoxycholate: 0.7 to 1 mg/kg intravenously once daily for 2 weeks

and

flucytosine: 25 mg/kg orally four times daily for 2 weeks

OR

amphotericin B liposomal: 3-4 mg/kg intravenously once daily for 2 weeks

and

fluconazole: 800-1200 mg orally once daily for 2 weeks

OR

amphotericin B deoxycholate: 0.7 to 1 mg/kg intravenously once daily for 2 weeks

and

fluconazole: 800-1200 mg orally once daily for 2 weeks

OR

fluconazole: 1200 mg orally/intravenously once daily for 2 weeks

and

flucytosine: 25 mg/kg orally four times daily for 2 weeks

Plus – antifungal consolidation therapy

Back
ACUTE
|
cryptococcal meningitis
Plus – 

antifungal consolidation therapy

Treatment recommended for ALL patients in selected patient group

After successful induction therapy, consolidation therapy with fluconazole can be started and should be continued for at least 8 weeks and at least until after antiretroviral therapy has been initiated and cerebrospinal fluid (CSF) cultures have sterilized.[1][76]

Itraconazole is an alternative option for patients who cannot tolerate fluconazole, or if fluconazole is unavailable.[1]

The US guidelines advise that individuals with positive CSF cultures but who have clinically improved after 2 weeks of induction therapy should receive a higher dose (1200 mg/day) of fluconazole for consolidation therapy, and have repeat lumbar puncture in another 2 weeks.[1] Alternatively, nonhospitalized individuals can receive flucytosine plus fluconazole for an additional 2 weeks before starting single-drug consolidation therapy.[1] The duration of consolidation therapy should be 8 weeks from the point at which CSF cultures are negative.[1][76]

Primary options

fluconazole: clinically stable and positive CSF cultures: 800 mg orally once daily; clinically stable and negative CSF cultures: 400 mg orally once daily

More

Secondary options

fluconazole: 1200 mg orally once daily

and

flucytosine: 25 mg/kg orally four times daily

OR

itraconazole: 200 mg orally twice daily

Plus – antifungal maintenance therapy

Back
ACUTE
|
cryptococcal meningitis
Plus – 

antifungal maintenance therapy

Treatment recommended for ALL patients in selected patient group

After the consolidation phase, the individual should be switched to low-dose fluconazole for long-term maintenance therapy.[1][76]

Treatment should continue for at least 1 year following initiation of antifungal therapy.

Itraconazole is an alternative option for patients who cannot tolerate fluconazole, or if fluconazole is unavailable.[1]

Maintenance therapy can be discontinued once the CD4 count is ≥100 cells/microliter, HIV RNA level is undetectable and symptoms have resolved. Maintenance therapy should be reinstituted if the CD4 count decreases to <100 cells/microliter.[1][242]​​[245]​​​[246][247]

Primary options

fluconazole: 200 mg orally once daily

More

Secondary options

itraconazole: 200 mg orally twice daily

Consider – therapeutic drainage of cerebrospinal fluid

Back
ACUTE
|
cryptococcal meningitis
Consider – 

therapeutic drainage of cerebrospinal fluid

Treatment recommended for SOME patients in selected patient group

Daily lumbar punctures may be needed for individuals with ongoing neurologic symptoms and increased intracranial pressure (≥25 cm of cerebrospinal fluid [CSF]). For individuals not responding to or tolerating daily lumbar punctures, CSF shunting should be considered.[1]

A repeat lumbar puncture should be performed after the first 2 weeks of treatment to ensure clearance of the organism from the CSF. If CSF cultures remain positive after 2 weeks of treatment, future relapse and generally less favorable outcomes are likely.[1]

cytomegalovirus

1st line – initial antiviral therapy

Back
ACUTE
|
cytomegalovirus
|
retinitis (immediate sight-threatening lesions)
1st line – 

initial antiviral therapy

Initial therapy should be individualized based on level of immunosuppression, location and severity of the lesion, adherence to treatment, and concomitant drugs.[1] Ganciclovir is usually the first choice for cytomegalovirus (CMV) infection or disease.

Systemic therapy reduces morbidity in the contralateral eye; this should be taken into consideration when making a decision regarding route of administration.[1]

Intravenous ganciclovir or oral valganciclovir with or without intravitreal ganciclovir or foscarnet is the preferred initial therapy for individuals with immediate sight-threatening lesions. Alternative options include intravitreal ganciclovir or foscarnet in combination with intravenous foscarnet or cidofovir (with probenecid and saline hydration therapy before and after cidofovir therapy).

An ophthalmologist familiar with cytomegalovirus retinitis should ideally be involved in management.[1]

Primary options

ganciclovir: 2 mg intravitreally weekly until lesion inactivity achieved

or

foscarnet: 2.4 mg intravitreally weekly until lesion inactivity achieved

-- AND --

ganciclovir: 5 mg/kg intravenously every 12 hours for 14-21 days

or

valganciclovir: 900 mg orally twice daily for 14-21 days

OR

ganciclovir: 5 mg/kg intravenously every 12 hours for 14-21 days

OR

valganciclovir: 900 mg orally twice daily for 14-21 days

Secondary options

ganciclovir: 2 mg intravitreally weekly until lesion inactivity achieved

or

foscarnet: 2.4 mg intravitreally weekly until lesion inactivity achieved

-- AND --

foscarnet: 60 mg/kg intravenously every 8 hours for 14-21 days; or 90 mg/kg intravenously every 12 hours for 14-21 days

OR

ganciclovir: 2 mg intravitreally weekly until lesion inactivity achieved

or

foscarnet: 2.4 mg intravitreally weekly until lesion inactivity achieved

-- AND --

cidofovir: 5 mg/kg intravenously once weekly for 2 weeks

-- AND --

probenecid: 2 g orally 3 hours before cidofovir dose, followed by 1 g given 2 hours and 8 hours after the dose

Plus – antiviral maintenance therapy

Back
ACUTE
|
cytomegalovirus
|
retinitis (immediate sight-threatening lesions)
Plus – 

antiviral maintenance therapy

Treatment recommended for ALL patients in selected patient group

Initial therapy should be followed by chronic maintenance therapy. Maintenance therapy can be safely discontinued in individuals with inactive disease and sustained CD4 count (>100 cells/microliter for ≥3-6 months); consultation with an ophthalmologist is recommended. Regular eye exams should be performed every 3 months in individuals who have discontinued maintenance therapy, for early detection of relapse, or immune recovery uveitis.[1]

Early relapse is most often caused by the limited intraocular penetration of systemically administered drugs.[248]

If individuals relapse while receiving maintenance therapy, reinduction with the same drug followed by reinstitution of maintenance therapy is recommended. Changing to an alternative drug at the time of first relapse should be considered if drug resistance is suspected or if side effects or toxicities interfere with optimal courses of the initial agent.

Primary options

valganciclovir: 900 mg orally once daily

Secondary options

ganciclovir: 5 mg/kg intravenously once daily

OR

foscarnet: 90-120 mg/kg intravenously once daily

OR

cidofovir: 5 mg/kg intravenously every 2 weeks

and

probenecid: 2 g orally 3 hours before cidofovir dose, followed by 1 g given 2 hours and 8 hours after the dose

1st line – antiviral therapy

Back
ACUTE
|
cytomegalovirus
|
retinitis (small peripheral lesions)
1st line – 

antiviral therapy

For small peripheral lesions, oral valganciclovir alone may be adequate.[1]

Systemic antiviral therapy is administered for the 3-6 months until antiretroviral treatment-induced immune recovery.[1]

Primary options

valganciclovir: 900 mg orally twice daily for 14-21 days, followed by 900 mg once daily

1st line – antiviral therapy

Back
ACUTE
|
cytomegalovirus
|
esophagitis or colitis
1st line – 

antiviral therapy

For gastrointestinal disease, oral valganciclovir, intravenous ganciclovir, or foscarnet for 21-42 days is recommended (or until signs and symptoms have resolved).

Intravenous ganciclovir is preferred with a transition to oral valganciclovir if tolerating and absorbing drugs. Oral valganciclovir is a first-line treatment if symptoms are not severe enough to interfere with oral absorption.

Foscarnet is an alternative agent for those with ganciclovir resistance or intolerance.

Maintenance therapy is usually not needed for cytomegalovirus esophagitis or colitis, but should be considered following relapses.[1]

Primary options

valganciclovir: 900 mg orally twice daily

OR

ganciclovir: 5 mg/kg intravenously every 12 hours, may switch to oral valganciclovir once patient can tolerate oral therapy

Secondary options

foscarnet: 60 mg/kg intravenously every 8 hours; or 90 mg/kg intravenously every 12 hours

1st line – antiviral therapy

Back
ACUTE
|
cytomegalovirus
|
neurologic disease
1st line – 

antiviral therapy

Combination regimen is used to stabilize disease and maximize response.

The optimal duration of therapy has not been established.[1]

Maintenance therapy should be continued for life unless there is evidence of immune recovery.

Primary options

ganciclovir: 5 mg/kg intravenously every 12 hours

and

foscarnet: 60 mg/kg intravenously every 8 hours; or 90 mg/kg intravenously every 12 hours

mucocutaneous candidiasis

1st line – azole antifungal or nystatin

Back
ACUTE
|
mucocutaneous candidiasis
|
oropharyngeal (initial episode)
1st line – 

azole antifungal or nystatin

Oral fluconazole is considered the drug of choice. Although itraconazole and posaconazole are as effective as fluconazole, they should only be used as second-line therapy.[249] Posaconazole is generally better tolerated than itraconazole.

Initial episodes of oropharyngeal candidiasis should be treated for 7-14 days. Chronic or prolonged use of azoles may promote development of resistance and also hepatotoxicity.

A single-dose fluconazole regimen has been proposed, but further studies are required to establish its efficacy.[260]

Primary options

fluconazole: 100 mg orally once daily

Secondary options

clotrimazole oropharyngeal: 10 mg orally (troche) five times daily

OR

miconazole oropharyngeal: 50 mg buccally once daily

OR

itraconazole: 200 mg orally (oral solution) once daily

OR

posaconazole: 400 mg orally (oral suspension) twice daily on day 1, followed by 400 mg once daily

OR

nystatin: 400,000 to 600,000 units (4-6 mL) orally four times daily

1st line – alternative azole antifungal

Back
ACUTE
|
mucocutaneous candidiasis
|
oropharyngeal (treatment-refractory)
1st line – 

alternative azole antifungal

Fluconazole-refractory oropharyngeal candidiasis may respond to itraconazole suspension or posaconazole. Voriconazole can also be used. In severe refractory cases, an intravenous echinocandin or amphotericin-B can be used.[249][250]

Patients may experience hepatotoxicity with more than 7-10 days of systemic azole treatment.

Primary options

posaconazole: 400 mg orally (oral suspension) twice daily

OR

itraconazole: 200 mg orally (oral solution) once daily

OR

voriconazole: 200 mg orally twice daily

Secondary options

caspofungin: 70 mg intravenously as a loading dose on day 1, followed by 50 mg every 24 hours

OR

micafungin: 100 mg intravenously every 24 hours

OR

anidulafungin: 200 mg intravenously as a loading dose on day 1, followed by 100 mg every 24 hours

OR

amphotericin B deoxycholate: 0.3 mg/kg intravenously every 24 hours

1st line – systemic antifungal

Back
ACUTE
|
mucocutaneous candidiasis
|
esophageal (initial episode)
1st line – 

systemic antifungal

For esophageal candidiasis, systemic antifungals are required for effective treatment. Oral or intravenous fluconazole is considered to be first-line therapy. For fluconazole-refractory disease, or oral itraconazole is considered second-line. Alternative options include voriconazole, isavuconazonium, anidulafungin, caspofungin, micafungin, and amphotericin.[1][249] 

A higher relapse rate of esophageal candidiasis with echinocandins (caspofungin, micafungin, anidulafungin) than with fluconazole has been reported.

The duration of treatment is 14-21 days.

Primary options

fluconazole: 100-400 mg orally/intravenously once daily

Secondary options

itraconazole: 200 mg orally (oral solution) once daily

OR

voriconazole: 200 mg orally/intravenously twice daily

OR

isavuconazonium sulfate: 200 mg orally as a loading dose, followed by 50 mg orally once daily; or 400 mg orally as a loading dose, followed by 100 mg orally once daily; or 400 mg orally once weekly

More

OR

caspofungin: 50 mg intravenously once daily

OR

micafungin: 150 mg intravenously once daily

OR

anidulafungin: 100 mg intravenously on day 1, followed by 50 mg once daily

OR

amphotericin B liposomal: 3-4 mg/kg intravenously once daily

1st line – alternative systemic antifungal

Back
ACUTE
|
mucocutaneous candidiasis
|
esophageal (treatment-refractory)
1st line – 

alternative systemic antifungal

Fluconazole-refractory disease may respond to itraconazole or posaconazole.[1]

Amphotericin-B deoxycholate or lipid formulation may also be effective. Echinocandin treatment (anidulafungin, caspofungin, or micafungin) may also be used.[1]

The duration of treatment is 14-21 days (28 days for posaconazole). Chronic or prolonged use of azoles may promote development of resistance and also hepatotoxicity.

Primary options

posaconazole: 400 mg orally (oral suspension) twice daily

OR

itraconazole: 200 mg orally (oral solution) once daily

Secondary options

anidulafungin: 100 mg intravenously on day 1, followed by 50 mg intravenously once daily

OR

caspofungin: 50 mg intravenously once daily

OR

micafungin: 150 mg intravenously once daily

OR

voriconazole: 200 mg orally/intravenously twice daily

OR

amphotericin B deoxycholate: 0.6 mg/kg intravenously once daily

OR

amphotericin B liposomal: 3-4 mg/kg intravenously once daily

1st line – systemic azole or topical antifungal or ibrexafungerp

Back
ACUTE
|
mucocutaneous candidiasis
|
vulvovaginal (uncomplicated)
1st line – 

systemic azole or topical antifungal or ibrexafungerp

Uncomplicated vulvovaginal candidiasis in women living with HIV usually responds to short-course oral fluconazole (a single dose) or itraconazole, or topical treatment with azoles for 3-7 days.

Ibrexafungerp (a triterpenoid antifungal) is a newer alternative that can be used where available for azole-resistant organisms or for individuals who cannot tolerate azole therapy.[1]

Primary options

fluconazole: 150 mg orally as a single dose

OR

clotrimazole vaginal: (1% cream) insert 5 g (one applicatorful) into the vagina once daily at night

OR

butoconazole vaginal: (2% cream) insert 5 g (one applicatorful) into the vagina once daily at night

OR

miconazole vaginal: (2% cream) insert 5 g (one applicatorful) into the vagina once daily at night

OR

tioconazole vaginal: (6.5% ointment) insert 5 g (one applicatorful) into the vagina once daily at night

OR

terconazole vaginal: (0.4% or 0.8% cream) insert 5 g (one applicatorful) into the vagina once daily at night

Secondary options

itraconazole: 200 mg orally (oral solution) once daily

OR

ibrexafungerp: 300 mg orally twice daily for 1 day

1st line – systemic azole or topical antifungal or ibrexafungerp

Back
ACUTE
|
mucocutaneous candidiasis
|
vulvovaginal (severe or recurrent disease)
1st line – 

systemic azole or topical antifungal or ibrexafungerp

Severe or recurrent episodes of vaginitis in women living with HIV require oral fluconazole or topical antifungal therapy for at least 7 days.[1]

For those with recurrent vulvovaginal candidiasis, oteseconazole (a newer tetrazole azole antifungal) and ibrexafungerp (a triterpenoid antifungal) are alternative options. These drugs are used as part of regimens (potentially with fluconazole) which aim to treat the acute episode plus treatment to reduce the incidence of recurrent episodes.[1]

Primary options

fluconazole: 100-200 mg orally once daily

OR

clotrimazole vaginal: (1% cream) insert 5 g (one applicatorful) into the vagina once daily at night

OR

butoconazole vaginal: (2% cream) insert 5 g (one applicatorful) into the vagina once daily at night

OR

miconazole vaginal: (2% cream) insert 5 g (one applicatorful) into the vagina once daily at night

OR

tioconazole vaginal: (6.5% ointment) insert 5 g (one applicatorful) into the vagina once daily at night

OR

terconazole vaginal: (0.4% or 0.8% cream) insert 5 g (one applicatorful) into the vagina once daily at night

Secondary options

itraconazole: 200 mg orally (oral solution) once daily

OR

oteseconazole: 600 mg orally once daily on day 1, followed by 450 mg once daily on day 2, then 150 mg once weekly for 11 weeks starting on day 14

OR

fluconazole: induction: 150 mg orally once daily on days 1, 4, and 7

and

oteseconazole: following fluconazole induction: 150 mg orally once daily on days 14-20, followed by 150 mg once weekly for 11 weeks starting on day 28

OR

fluconazole: induction: 150 mg orally every 72 hours for 3 doses

and

ibrexafungerp: following fluconazole induction: 300 mg orally twice daily for 1 day per month for 6 months (take on the same day of each month)

coccidioidomycosis

1st line – azole antifungal

Back
ACUTE
|
coccidioidomycosis
|
mild-moderate pulmonary disease
1st line – 

azole antifungal

For clinically mild-to-moderate pulmonary coccidioidomycosis (e.g., focal coccidioidal pneumonia), oral fluconazole or itraconazole are the preferred agents for immunocompetent and immunocompromised individuals.[1][251]

Alternative azoles include isavuconazonium, voriconazole, and posaconazole, although data are limited.[1][252]

Relapse is common in all individuals with coccidioidomycosis, regardless of immune status, and all individuals should be managed with an experienced infectious diseases physician.

Primary options

fluconazole: 400 mg orally once daily

OR

itraconazole: 200 mg orally three times daily for 3 days, followed by 200 mg twice daily

Secondary options

voriconazole: 400 mg orally twice daily on day 1, followed by 200 mg twice daily

OR

posaconazole: 300 mg orally (delayed-release) twice daily on day 1, followed by 300 mg once daily

OR

isavuconazonium sulfate: 372 mg orally three times daily for 6 doses, followed by 372 mg once daily

1st line – amphotericin-B or azole antifungal

Back
ACUTE
|
coccidioidomycosis
|
severe pulmonary disease or extrapulmonary nonmeningeal coccidioidomycosis
1st line – 

amphotericin-B or azole antifungal

For severe pulmonary coccidioidomycosis (e.g., diffuse pulmonary infiltrates) or for extrapulmonary nonmeningeal coccidioidomycosis and for those with a CD4 count less than 50 cells/microliter, intravenous amphotericin-B deoxycholate or liposomal amphotericin-B should be promptly administered. Therapy can be switched to an oral azole after clinical improvement and should be continued long term, regardless of the CD4 count.[1]

Primary options

amphotericin B deoxycholate: 0.7 to 1 mg/kg intravenously every 24 hours

OR

amphotericin B liposomal: 3-5 mg/kg intravenously every 24 hours

1st line – azole antifungal or intrathecal amphotericin-B

Back
ACUTE
|
coccidioidomycosis
|
meningeal coccidioidomycosis
1st line – 

azole antifungal or intrathecal amphotericin-B

For meningeal coccidioidomycosis, high-dose intravenous or oral fluconazole is preferred. Other azoles, such as itraconazole, can be given as alternatives, although there is less data and less clinical experience.[1][253]

For refractory cases, intrathecal amphotericin-B may be required. Consultation with an experienced specialist is recommended. Intrathecal therapy should be administered by a clinician very experienced in this drug delivery technique. Consult a specialist for guidance on intrathecal dose.

Primary options

fluconazole: 800-1200 mg intravenously every 24 hours

Secondary options

itraconazole: 200 mg orally two to three times daily

OR

voriconazole: 200-400 mg orally twice daily

OR

posaconazole: 300 mg orally (delayed-release) twice daily on day 1, followed by 300 mg once daily

OR

isavuconazonium sulfate: 372 mg orally three times daily for 6 doses, followed by 372 mg once daily

disseminated histoplasmosis

1st line – azole antifungal

Back
ACUTE
|
disseminated histoplasmosis
|
mild-moderate
1st line – 

azole antifungal

Disseminated disease is defined as clinical illness that fails to improve after 3 weeks of observation and is accompanied by signs and symptoms of extrapulmonary involvement. Progressive disseminated histoplasmosis has a high fatality rate without therapy. Treatment is the same for immunocompetent and immunocompromised patients.[1][203]

Oral itraconazole is the preferred treatment for patients with mild to moderate disseminated disease, and is given for at least 12 months.[1][203]

Voriconazole and posaconazole have been successfully used to treat immunocompromised individuals with histoplasmosis, and these drugs can be considered as alternative agents for those individuals unable to tolerate itraconazole.[1][203]

Fluconazole demonstrates lower activity against the fungus and is less effective than itraconazole, and there have been reports of resistance emerging among patients receiving fluconazole therapy.[1][27]​ Fluconazole is therefore reserved for patients who are intolerant of or refractory to other azoles.

Therapeutic drug monitoring is recommended with azole antifungals.[1][203]

Primary options

itraconazole: 200 mg orally three times daily for 3 days, followed by 200 mg orally twice daily

Secondary options

voriconazole: 400 mg orally twice daily on day 1, followed by 200 mg twice daily

OR

posaconazole: 300 mg orally (delayed-release tablet) twice daily on day 1, followed by 300 mg once daily

Tertiary options

fluconazole: 800 mg orally once daily

1st line – amphotericin-B

Back
ACUTE
|
disseminated histoplasmosis
|
severe
1st line – 

amphotericin-B

Disseminated disease is defined as clinical illness that fails to improve after 3 weeks of observation and is accompanied by signs and symptoms of extrapulmonary involvement. Progressive disseminated histoplasmosis has a high fatality rate without therapy. Treatment is the same for immunocompetent and immunocompromised patients.[1][203]

For individuals with severe disseminated histoplasmosis, including those who are hypoxemic or require ventilatory support, liposomal amphotericin-B is the preferred initial treatment. Other formulations of amphotericin-B may be used if liposomal amphotericin-B is unavailable or not tolerated. Therapy should be initiated with amphotericin-B for 1-2 weeks and transitioned to oral itraconazole (or an alternative azole antifungal) after clinical stabilization to complete a 12-month course.[1][203]

Primary options

amphotericin B liposomal: 3 mg/kg/day intravenously

Secondary options

amphotericin B lipid complex: 5 mg/kg/day intravenously

OR

amphotericin B deoxycholate: 0.7 to 1 mg/kg/day intravenously

Plus – azole antifungal

Back
ACUTE
|
disseminated histoplasmosis
|
severe
Plus – 

azole antifungal

Treatment recommended for ALL patients in selected patient group

Following antifungal induction therapy, individuals should be transitioned to oral itraconazole (or an alternative azole antifungal) after clinical stabilization to complete a 12-month course.

In people living with HIV, itraconazole can safely be discontinued after at least 1 year if they are receiving highly active antiretroviral therapy, CD4 count is >150 cells/mL, blood culture results are negative, and Histoplasma capsulatum serum and urine antigen levels are <2 nanograms/mL.[254][258][259]

Urine H capsulatum antigen levels should be taken monthly to monitor response to therapy and followed for 12 months to detect disease relapse. Up to 10% to 15% of individuals experience relapse despite treatment, which is an indication for long-term maintenance therapy with itraconazole.[256][257]

Primary options

itraconazole: 200 mg orally three times daily for 3 days, followed by 200 mg orally twice daily

Secondary options

voriconazole: 400 mg orally twice daily on day 1, followed by 200 mg orally twice daily

OR

posaconazole: 300 mg orally (delayed-release tablet) twice daily on day 1, followed by 300 mg once daily

Tertiary options

fluconazole: 800 mg orally once daily

Consider – ventilatory support

Back
ACUTE
|
disseminated histoplasmosis
|
severe
Consider – 

ventilatory support

Treatment recommended for SOME patients in selected patient group

Individuals may become hypoxemic and require ventilatory support.

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