Acute General RxAcute management of opportunistic infections is summarized in Table 4 and reviewed elsewhere in this text under specific AIDS-related disorders. For management of AIDS-related malignancies, please refer to the specific malignancy elsewhere in this text.
TABLE 4 Treatments for the Most Common Opportunistic Infections in Critically Ill HIV-Positive Patients
| Opportunistic Infection | First-Line Regimen for Severe Cases | Main Alternatives | Adjunctive Therapies | Timing of cART Introduction |
| PCP pneumonia | - TMP (15-20 mg/kg/d) and SMX (75-100 mg/kg/d) IV q6h or q8h
- Switch to PO after clinical improvement
- Total treatment duration: 3 wk (then switch to secondary prophylaxis dosinga)
- No leucovorin supplementationb
| Pentamidine 4 mg/kg IV once daily (patients with TMP or SMX adverse events such as allergy or hemolysis because of glucose-6-phosphate dehydrogenase deficiency) | - Corticosteroids if PaO2<70 mm Hg (room air)
- Prednisone PO:
- Days 1-5: 40 mg BID
- Days 6-10: 40 mg daily
- Days 11-21: 20 mg daily
- Alternative:
- methylprednisolone IV (75% of prednisone dose)
| Within 2 wk |
| Tuberculosis (drug-susceptible M. tuberculosis) | - •Intensive phase (2 mo): isoniazid + rifampin or rifabutin + pyrazinamide + ethambutol
- •Continuation phase: isoniazid + rifampin or rifabutin
- •Total treatment duration:
- Pulmonary TB: 6-9 mo
- Extrapulmonary TB with CNS involvement: 9-12 mo
- Extrapulmonary TB with bone or joint involvement: 6-9 mo
- Extrapulmonary TB at other sites: 6 mo
| Consult an ID specialist | - •CNS disease: dexamethasone 0.3-0.4 mg/kg/d for 2-4 wk, then taper by 0.1 mg/kg per wk until 0.1 mg/kg, then 4 mg/d and taper by 1 mg/wk; total duration of 12 wk
- •Pericardial disease: prednisone or prednisolone (e.g., 60 mg PO daily with weekly tapering over 6 wk)
| - •Active TB without CNS involvement:
- •Within 2 wk for patients with CD4 cells <50/mL
- •Within 8 wk for patients with CD4 cells ≥50/mL
- •Active TB with CNS involvement: deferred initiation (high risk of severe IRIS)
- •Close collaboration with ID specialists
|
| Toxoplasmosis | - •Pyrimethamine 200 mg PO once, then pyrimethamine 50-75 mg PO daily + sulfadiazine 1000-1500 mg PO q6h + leucovorin 10-25 mg PO daily
- •Total treatment duration: at least 6 wk (then switch to chronic maintenance therapya)
| - •Pyrimethamine (with leucovorin) plus clindamycin 600 mg IV or PO q6h
- •TMP 5 mg/kg and SMX 25 mg/kg IV or PO BID
| - •Corticosteroids if cerebral lesions with mass effect
- •Anticonvulsants only if seizures (no primary prevention)
| - •No recommendation, because of insufficient data (usually within 2-3 wk)
|
| Cryptococcus infections | - •Induction therapy (at least 2 wk): liposomal amphotericin B 3-4 mg/kg IV daily plus flucytosine 25 mg/kg QID
- •Consolidation therapy (at least 8 wk) after clinical improvement and sterilization of CSF cultures: fluconazole 400 mg PO or IV once daily
- •Maintenance therapy (at least 1 yr): fluconazole 200 mg PO
| Induction therapy: fluconazole (400-800 mg/d) may replace either liposomal amphotericin B or flucytosine | Corticosteroids may be deleterious in patients with CNS disease and are not recommended. | - CNS involvement: 2-10 wk after initiation of specific therapy (longer delay if high intracranial pressure)
- Other localizations: 2-4 wk after initiation of specific therapy
|
| Histoplasmosis | - Induction therapy (at least 2 wk):
- liposomal amphotericin B 3 mg/kg/d IV-If confirmed meningitis: increase dosage to 5 mg/kg/d and extend induction to 4-6 wk
- Maintenance therapy: itraconazole 200 mg PO TID for 3 days, then BID for at least 12 mo
| Fluconazole (400 md/d PO) may replace itraconazole for long-term suppressive therapy | - | As soon as possible |
| Disseminated MAC disease | Clarithromycin 500 mg PO twice daily + ethambutol 15 mg/kg PO daily or azithromycin 500-600 mg + ethambutol 15 mg/kg PO daily | Consult an infectious disease specialist | - | After completion of the second week of MAC-directed therapy |
| Addition of a third or fourth drug (rifabutin, amikacin, fluoroquinolone) should be considered for patients with CD41 T cells <50/mL, high mycobacterial loads (>2 log CFU/ml of blood), or in the absence of effective cART | | | |
| CMV infection | - Ganciclovir 5 mg/kg IV q12h
- Role of oral valganciclovir: not established
- Optimal treatment duration: not established
| Foscarnet 60 mg/kg IV q8h or 90 mg/kg IV q12h | - | No recommendation, because of insufficient data (usually within 2 wk) |
| PML | cART | - | - | As soon as possible |
BID, Twice a day; cART, Combination antiretroviral therapy; CFU, colony-forming unit; CMV, cytomegalovirus; CNS, central nervous system; CSF, cerebrospinal fluid; HIV, human immunodeficiency virus; IRIS, immune reconstitution inflammatory syndrome; IV, intravenous, intravenously; MAC, Mycobacterium avium complex; PaO2, arterial partial pressure of oxygen; PCP, Pneumocystis jiroveci; PML, progressive multifocal encephalopathy (caused by JC virus); PO, per os; SMX, sulfamethoxazole; TB, tuberculosis; TID, three times a day; TMP, trimethoprim. Society of America for the management of opportunistic infections in adults with HIV.
Adapted from the guidelines of the Centers for Disease Control and Prevention, the National Institutes of Health, and the Infectious Diseases Society. In Vincent JL et al: Textbook of critical care, ed 8, Philadelphia, 2024, Elsevier.
Chronic RxFor all HIV-infected patients, particularly those meeting the case definition of AIDS:
- •Preventive therapy for Pneumocystis jiroveci pneumonia, Mycobacterium avium complex (MAC) disease, and Toxoplasma gondii encephalitis are summarized in Table 5. With appropriate antiretroviral therapy, many patients experience substantial restoration of cellular immune function. Preventive therapy for Pneumocystis jiroveci can be safely stopped if the CD4 cell count rises above 200 for at least 3 mo.
- •Based on the Department of Health and Human Services (DHHS) Guidelines, active antiretroviral therapy (ART) should be started regardless of CD4 cell count. Individuals with CD4 cell counts <350 and especially CD4 cell counts <200 should be strongly encouraged to start ART in a timely fashion.
- •ART usually includes three-drug combinations of:
- 1.Nucleoside reverse transcriptase inhibitors (NRTI): Tenofovir disoproxil fumarate (TDF), tenofovir alafenamide fumarate (TAF), lamivudine (3TC), emtricitabine (FTC), and abacavir (ABC). Older drugs such as zidovudine (AZT), didanosine (ddI), and stavudine (d4T) are generally not recommended.
- 2.Protease inhibitors (PI): Darunavir (preferred) or atazanavir.
- 3.Nonnucleoside reverse transcriptase inhibitors (NNRTI): Nevirapine, efavirenz (EFV), etravirine, doravirine, and rilpivirine.
- 4.Integrase inhibitors: Raltegravir, elvitegravir, bictegravir, dolutegravir, and cabotegravir.
- 5.Others: Maraviroc, enfuvirtide, ibalizumab, and fostemsavir.
TABLE 5 Prophylaxis to Prevent First Episode of Selected Opportunistic Infections
| Pathogen | Indication | First-Choice Therapy | Alternative |
| Pneumocystis jiroveci pneumonia (PCP) | - •CD4+<200 cells/mL or oropharyngeal candidiasis
- •CD4+<14% or history of AIDS-defining illness
- •CD4+>200 cells/mL but <250 cells/mL if monitoring is not possible every 1-3 mo
| TMP-SMZ | - TMP-SMZ
- Dapsone
- Dapsone + pyrimethamine + leucovorin
- Aerosolized pentamidine
- Atovaquone
- Atovaquone + pyrimethamine + leucovorin
|
| Toxoplasma gondii encephalitis | - •Toxoplasma IgG-positive patients with CD4+ count <100 cells/mL
- •Seronegative patients receiving PCP prophylaxis not active against toxoplasmosis should have Toxoplasma serology retested if CD4+ count declines to <100 cells/mL
- •Initiate prophylaxis if seroconversion occurs.
| TMP-SMZ | - TMP-SMZ
- Dapsone + pyrimethamine + leucovorin
- Dapsone + pyrimethamine + leucovorin
- Atovaquone ± pyrimethamine + leucovorin
|
| Disseminated Mycobacterium avium complex (MAC) disease | - •CD4+ count <50 cells/mL (after active MAC infection is ruled out)
| Azithromycin or Clarithromycin | Rifabutin (adjust dose on basis of ART interactions); rule out active TB before rifabutin is started. |
ART, Antiretroviral therapy; TB, tuberculosis; TMP-SMZ, trimethoprim-sulfamethoxazole.
Adapted from Kaplan JE et al: Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. Available at https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5804a1.htm. In Walls RM et al: Rosen’s emergency medicine, concepts and clinical practice, ed 10, Philadelphia, 2023, Elsevier.
The medications ritonavir or cobicistat are usually used in combination with other protease inhibitors or integrase inhibitors to obtain more sustained drug levels. Usual initial dosing regimens include two NRTIs and an NNRTI or PI or integrase inhibitor. Two-drug regimens with dolutegravir and lamivudine can be considered in certain clinical situations. Currently, integrase inhibitors are recommended as first-line drugs because of tolerability. Examples of initial regimens recommended by the guidelines:
- •Bictegravir/tenofovir alafenamide/emtricitabine
- •Dolutegravir/abacavir/lamivudine (in patients who are HLA-B5701 NEGATIVE)
- •Dolutegravir plus tenofovir/emtricitabine (tenofovir-based formulations can include tenofovir disoproxil fumarate [TDF] or tenofovir alafenamide [TAF])
- •Dolutegravir and lamivudine (two-drug regimen). This regimen should not be used in individuals with HIV RNA >500,000 copies/ml, HBV coinfection, or in whom ART is to be started before the results of HIV genotypic resistance testing for reverse transcriptase or HBV testing are available.
All these drugs have unique and class-specific side effects and require careful and expert follow-up to achieve optimal antiviral effects, ensure compliance, and maintain efficacy. Antiviral response should be monitored by baseline HIV viral load and CD4 count and repeat measurement at 2 wk and 4 wk into treatment and then periodically (3 to 6 mo) to ensure viral suppression.
- •The approach to a patient with CNS signs and symptoms is described in Fig. E3, and Fig. E4 describes the management of CNS mass lesions.
- •Genotypic resistance testing is strongly encouraged for all patients initiating treatment and for any patient failing antiretroviral therapy. Poor adherence to therapy, however, often underlies virologic failure.
Figure E3 Diagnostic Approach and Management Algorithm for Human Immunodeficiency Virus (HIV)-Infected Patients with Central Nervous System (CNS) Symptoms or Signs that Might Potentially Be Toxoplasmic Encephalitis (TE)
AFB, Acid-fast bacilli; CT, computed tomography; IgG, immunoglobulin G; MRI, magnetic resonance imaging; PCR, polymerase chain reaction.
(From Bennett JE et al: Mandell, Douglas, and Bennett’s principles and practice of infectious diseases, ed 9, Philadelphia, 2020, Elsevier.)
Figure E4 Management of the Human Immunodeficiency Virus (HIV) Type 1-Infected Patient with Central Nervous System (CNS) Mass Lesions
The elements in italics represent data that contribute to the decision-making process (see text for details). CSF, Cerebrospinal fluid; CT, computed tomography; LP, lumbar puncture; MRI, magnetic resonance imaging; SPECT, single-photon emission computed tomography; TE, Toxoplasma encephalitis.
(From Bennett JE et al: Mandell, Douglas, and Bennett’s principles and practice of infectious diseases, ed 9, Philadelphia, 2020, Elsevier.)
DispositionThe outlook for HIV has changed radically since the advent of ART from an essentially fatal disease to a chronic medical illness compatible with long-term survival and remarkably good quality of life. Patients should be aggressively treated for severe illnesses as outcomes following ICU admissions remain good. This is accomplished through expert and continuous follow-up, use of ART, and careful detail to compliance to medications and lifestyle modification.
