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Fast Facts
A brief refresher with useful tables, figures, and research summaries
Opportunistic Infections
Opportunistic infection refers to illness caused by a microorganism that does not usually cause disease in immunocompetent individuals but is pathogenic in those with compromised immune systems.
A variety of immunocompromised patients are at risk for opportunistic infections (OIs), including patients with HIV/AIDS, patients who have undergone solid-organ or bone-marrow transplantation, and those taking high-dose glucocorticoids or immune modulators (e.g., for rheumatologic diseases, inflammatory bowel disease, multiple sclerosis, and obstructive airway diseases). Recognizing opportunistic infections early and ensuring adequate prophylaxis are crucial for mitigating their complications. In this section, we will cover:
Common Opportunistic Infections
Immunocompromised patients are at increased risk for common infections in addition to the rarer pathogens. The specific organisms that a patient is susceptible to vary based on the patient’s underlying illness. Common opportunistic infections in immunocompromised patients include:
Pneumocystis jirovecii pneumonia (formerly Pneumocystis carinii pneumonia; PCP)
tuberculosis (TB)
Mycobacterium avium complex (MAC)
Endemic mycoses: histoplasmosis, Coccidioides, Blastomyces, Cryptococcus, Talaromyces marneffei (endemic in Southeast Asia)
other fungal infections: yeast (e.g., Candida) and molds (e.g., Aspergillus or mucormycosis)
cytomegalovirus (CMV)
herpes simplex virus (HSV) and varicella-zoster virus (VZV)
Epstein-Barr virus (EBV)
BK virus
JC virus
hepatitis B reactivation
Prophylaxis for Opportunistic Infections in Adults with HIV
Prophylactic Antibiotics
Antiretroviral agents and prophylactic antibiotics have significantly reduced the frequency of opportunistic infections in patients with HIV/AIDS. A patient’s CD4-cell count correlates with the likelihood of contracting an OI, and those with normal CD4-cell counts are not typically considered to be immunocompromised. The following table provides a simple guide for choosing prophylaxis in patients with HIV/AIDS:
Infection | When to Start Prophylaxis | First-Line Option | Alternatives |
---|---|---|---|
Pneumocystis jirovecii pneumonia (PJP) |
CD4-cell count <200 cells/mm3 or CD4% <14% |
Trimethoprim-sulfamethoxazole (TMP-SMX) single-strength (SS) or double-strength (DS) daily |
Dapsone, aerosolized pentamidine, or atovaquone |
Toxoplasmosis | CD4-cell count <100 cells/mm3 and positive Toxoplasma IgG |
TMP-SMX DS daily | Dapsone + pyrimethamine + leucovorin, or atovaquone |
Mycobacterium avium complex (MAC) |
Primary prophylaxis against disseminated MAC disease is not recommended for adults and adolescents with HIV who immediately initiate antiretroviral therapy (ART), regardless of CD4-cell count. Individuals with CD4-cell count <50 and not on fully suppressive ART should still receive MAC prophylaxis |
Rifabutin | |
Latent tuberculosis infection (LTBI)* | Positive purified protein derivative (PPD) test (≥5 mm) or positive interferon- gamma release assay (IGRA) |
Isoniazid plus rifapentine once weekly for 3 months Or Rifampin once daily for 4 months Or Isoniazid plus rifampin daily for 3 months |
Isoniazid daily for 6 or 9 months |
Vaccinations
In addition to prophylaxis with drugs, vaccination is another vital component for keeping patients with HIV/AIDS healthy. The following table summarizes general immunization recommendations from the Centers for Disease Control (CDC) for patients with HIV. Other vaccines may be indicated based on additional risk factors. The complete National Institutes of Health recommendations for prophylaxis, treatment, and vaccination of patients with HIV/AIDS can be found here.
Recommended Vaccination for Patients with HIV | ||
---|---|---|
Influenza | 1 dose annually (live attenuated influenza vaccine [LAIV] not recommended) | |
Pneumococcal disease | Either 1 dose of 15-valent pneumococcal conjugate vaccine (PCV15) followed by a dose of 23-valent pneumococcal polysaccharide vaccine (PPSV23), OR a single dose of PCV20* | |
Tetanus-diphtheria-acellular pertussis (Tdap) | 1 dose Tdap, Td booster every 10 years | |
Measles-mumps-rubella (MMR) | Not recommended if CD4-cell count <200 cells/mm3 | 1 or 2 doses if CD4-cell count ≥200 cells/mm3 |
Varicella-zoster virus | Not recommended if CD4-cell count <200 cells/mm3 | 2 doses if CD4-cell count ≥200 cells/mm3 |
Shingles (herpes zoster) | 2 doses at age ≥19 years | |
Human papillomavirus (HPV) | 3 doses through age 26 years | |
Hepatitis B Hepatitis A |
2 or 3 doses depending on vaccine | |
Meningococcal ACWY vaccines | 2 doses, booster every 5 years | |
Covid-19 | See CDC Guidance |
Prophylaxis for Opportunistic Infections After Solid-Organ Transplantation
Initial considerations for infection and prophylaxis should be started at the time of transplantation. The following table summarizes recommendations for the prevention of opportunistic infections in solid-organ transplant recipients with HIV.
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(Source: Infections in Solid Organ Transplant HIV-Infected Patients. Clin Microbiol Infect 2014.)
The following are prophylaxis recommendations from the American Society of Transplantation Infectious Diseases Community of Practice for solid-organ transplant recipients from the American Society of Transplantation infectious diseases guidelines.
Valganciclovir is recommended for CMV prophylaxis in the following patients (“D” denotes donor serologic status and “R” denotes recipient serologic status): D+/R−, D+/R+, and D−/R+. Duration of prophylaxis varies by organ transplantation center and risk of developing CMV infection and is usually a minimum of 3 months (but often closer to 6 or 12 months) after transplantation and is restarted for a few months after postrejection treatment with antithymocyte globulin.
TMP-SMX is typically administered for 6 to 12 months after transplantation, to prevent PJP pneumonia as well toxoplasmosis. Alternative PJP prophylaxis agents include dapsone, atovaquone, or inhaled pentamidine.
Oral clotrimazole lozenges, nystatin, or fluconazole are given as needed after transplantation or a month after antithymocyte globulin.
Research
Landmark clinical trials and other important studies
Limaye AP et al. JAMA 2023.
This randomized, phase 3, noninferiority trial compared letermovir to standard-of-care valganciclovir for cytomegalovirus prophylaxis in CMV-negative transplant recipients from CMV-positive donors. Letermovir was noninferior to valganciclovir and was associated with lower rates of leukopenia.
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Van Delden C et al. Clin Infect Dis 2020.
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Swindells S et al. N Engl J Med 2019.
This randomized, open-label, phase 3, noninferiority trial compared the efficacy and safety of a one-month regimen of daily rifapentine plus isoniazid (one-month group) versus 9 months of isoniazid alone (9-month group) in HIV-infected patients. The one-month regimen of rifapentine plus isoniazid was noninferior to 9 months of isoniazid alone for preventing tuberculosis in HIV-infected patients.
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Martinson NA et al. N Engl J Med 2011.
This randomized, controlled trial looking at three new regimens for latent TB compared to standard 6-month isoniazid therapy found these regimens to be effective and nonsuperior to standard therapy with a potential advantage in ease of adherence.
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Reviews
The best overviews of the literature on this topic
Karuthu S and Blumberg EA. Clin J Am Soc Nephrol 2012.
![[Image]](content_item_thumbnails/CJN.04410512.jpg)
Hirsch HH and Snydman DR. Clin Infect Dis 2005.
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Thomas CF and Limper AH. N Engl J Med 2004.
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Guidelines
The current guidelines from the major specialty associations in the field
National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association, and Infectious Diseases Society of America Panel on Opportunistic Infections in Adults and Adolescents with HIV 2023. Accessed September 20, 2023.
![[Image]](content_item_thumbnails/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections.jpg)
Smith DJ et al. Clin Infect Dis 2023.
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Sterling TR et al. MMWR Morb Mortal Wkly Rep 2020.
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Blumberg EA et al. Clin Transplant 2019.
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Nation HIV Curriculum 2023.
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