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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:

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:

Prophylaxis for the Prevention of Opportunistic Infections 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.

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

Research

Letermovir vs Valganciclovir for Prophylaxis of Cytomegalovirus in High-Risk Kidney Transplant Recipients

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.

Read the NEJM Journal Watch Summary

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One Month of Rifapentine plus Isoniazid to Prevent HIV-Related Tuberculosis

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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New Regimens to Prevent Tuberculosis in Adults with HIV Infection

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

Reviews

Common Infections in Kidney Transplant Recipients

Karuthu S and Blumberg EA. Clin J Am Soc Nephrol 2012.

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BK Virus: Opportunity Makes a Pathogen

Hirsch HH and Snydman DR. Clin Infect Dis 2005.

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Medical Progress: Pneumocystis Pneumonia

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

Guidelines

Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV

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.

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National HIV Curriculum

Nation HIV Curriculum 2023.

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