HIV AIDS opportunistic infections

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alejandro Lemor, M.D. [2]

Overview

Before the widespread use of potent combination antiretroviral therapy (ART), opportunistic infections (OIs), which have been defined as infections that are more frequent or more severe because of immunosuppression in HIV-infected persons, were the principal cause of morbidity and mortality in this population. In the early 1990s, the use of chemoprophylaxis, immunization, and better strategies for managing acute OIs contributed to improved quality of life and improved survival. However, the widespread use of ART starting in the mid-1990s has had the most profound influence on reducing OI-related mortality in HIV-infected persons in those countries in which these therapies are accessible and affordable.

HIV Opportunistic Infections

Bacteria

Disease	Description	Clinical Findings	Diagnosis	Prevention / Prophylaxis	Treatment
Mycobacterium avium complex (MAC)	M.avium is the etiologic agent in 95% of patients with MAC disease The greatest risk of disease occurs among patients with a CD4+ <50 cells/µL	Fever, night sweats, weight loss, fatigue, diarrhea, and abdominal pain.	Isolation of MAC from cultures of blood, lymph node or bone marrow.	Prophylaxis is indicated when CD4 < 50 cells/µL Azithromycin 1200 mg PO once weekly, OR Clarithromycin 500 mg PO BID	Clarithromycin 500 mg PO twice daily + ethambutol 15 mg/kg PO daily , OR Azithromycin 500–600 mg + ethambutol 15 mg/kg PO daily (Testing of susceptibility to clarithromycin or azithromycin is recommended)
Respiratory Disease
Enteric Infections	The most common routinely cultured enteric bacteria among HIV-infected adults in the United States are Salmonella, Shigella, and Campylobacter. Other pathogens include E. coli and C. difficile.	Severe and prolonged diarrheal disease, potentially associated with fever, bloody diarrhea, and weight loss.	The diagnosis of Gram-negative bacterial enteric infection is established through cultures of stool and blood. Stool sample for C. difficile toxin or polymerase chain reaction assay (if recent antibiotic use)	Antimicrobial prophylaxis to prevent bacterial enteric illness usually is not recommended.	Treatment should be pathogen specific. Empiric therapy: Ciprofloxacin 500–750 mg PO q12h Oral or IV hydration therapy as appropriate.
Bacillary Angiomatosis	B. henselae and B. quintana infections have been identified in HIV- infected patients The greatest risk of disease occurs among patients with a CD4+ <50 cells/µL	Cutaneous lesions (red, globular and non-blanching, with a vascular appearance), sub-cutaneous nodules.	Histopathologic examination of biopsied tissue	Primary chemoprophylaxis for Bartonella-associated disease is not recommended	Doxycycline 100 mg PO or IV q12h, OR Erythromycin 500 mg PO or IV q6h
Syphilis	Treponema pallidum is the causative pathogen.	Single painless nodule	Serologic tests: VDRL, RPR, FTA-ABS, TP-PA Darkfield microscopy and tests to detect T. pallidum in lesion exudates or tissue (biopsy with silver stain) are definitive for diagnosing early syphilis
Table adapted from Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents

Virus

Disease	Description	Clinical Findings	Diagnosis	Prevention / Prophylaxis	Treatment
Cytomegalovirus Disease	The greatest risk of disease occurs among patients with a CD4+ <50 cells/µL	Retinitis is the most common clinical manifestation of CMV end-organ disease Colitis occurs in 5% to 10% of patients with AIDS and CMV end-organ disease, clinical manifestations include weight loss, anorexia, abdominal pain, diarrhea, and malaise. Esophagitis occurs in a small percentage of patients	CMV viremia can be detected by PCR, antigen assays, or culture	CMV end-organ disease is best prevented by using ART to maintain CD4 count >100 cells/uL Ganciclovir or valganciclovir primary prophylaxis is not recommended. Some specialists recommend yearly funduscopic examination in patients with CD4 < 50 cells/uL	Preferred Regimen: Valganciclovir 900 mg PO daily For sight threatening lesions: Add intravitreal injections of ganciclovir or foscarnet to normal regimen.
Herpes Simplex Virus Disease
Varicella-Zoster Virus Diseases
Human Herpesvirus-8 Disease
Human Papillomavirus Disease
JC Virus Infection
Table adapted from Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents

Fungus

Disease	Description	Clinical Findings	Diagnosis	Prevention / Prophylaxis	Treatment
Pneumocystis Pneumonia (Click here for more information)	Caused by the fungus Pneumocystis jirovecii. 90% of cases occurred among patients with CD4+ <200 Incidence among HIV patients: 2-3 cases per 100 person-year	Subacute onset of progressive dyspnea, fever, nonproductive cough, and chest discomfort that worsens within days to weeks. Tachypnea, tachycardia, and diffuse dry rales are found in the physical examination.	Clinical presentation, blood tests, or chest x-rays are not pathognomonic for PCP. BAL or induced sputum samples are required for a definite diagnosis.	Start TMP-SMX prophylaxis when CD4+ <200 cells/µL or history of oropharyngeal candidiasis. Discontinue prophylaxis when CD4+ is >200 cells/µL for >3 month.	TMP-SMX Administer adjunctive corticosteroids in patients with pO2 <70 mm Hg or arterial-alveolar O2 gradient >35 mm Hg In patients not on ART, ART should be initiated, when possible, within 2 weeks of diagnosis of PCP
Mucocutaneous Candidiasis
Cryptococcosis
Histoplasmosis
Coccidioidomycosis
Aspergillosis
Table adapted from Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents

Parasite

Disease	Description	Clinical Findings	Diagnosis	Prevention / Prophylaxis	Treatment
Toxoplasma gondii Encephalitis (Click here for more information)	Caused by the protozoan Toxoplasma gondii The greatest risk of disease occurs among patients with a CD4+ <50 cells/µL Primary infection occurs after eating undercooked meat containing tissue cysts or ingesting oocysts that have been shed in cat feces and have sporulated in the environment	Focal encephalitis with headache, confusion, or motor weakness and fever	Diagnosis is done with IgG antibodies. CT scan or MRI of the brain will typically show multiple contrast-enhancing lesions, often with associated edema. Definite diagnosis requires a brain biopsy. PET is helpful to distinguish between toxoplasmosis and primary CNS lymphoma.	Start TMP-SMX prophylaxis when CD4+ <100 cells/µL Discontinue prophylaxis when CD4+ is >200 cells/µL for >3 month.	Administer: Pyrimethamine, PLUS Sulfadiazine, PLUS Leucovorin
Cryptosporidiosis (Click here for more information)	Caused by the protozoan Cryptosporidium (C. hominis, C. parvum, and C. meleagridis) The greatest risk of disease occurs among patients with a CD4+ <100 cells/µL	Acute or subacute onset of watery diarrhea, nausea, vomiting, lower abdominal pain. Fever is seen in 1/3 of patients.	Microscopic examination of oocysts in stool with direct immunofluorescence.	Initiate ART Education of possibles ways of transmission (infected patients, diapers, animals) Avoid direct contact of pet stool Scrupulous handwashing is recommended.	Initiate or optimize ART for immune restoration to CD4 count >100 cells/mm3 Aggressive oral and/or IV rehydration and replacement of electrolyte loss, and symptomatic treatment of diarrhea with anti- motility agent.
Microsporidiosis	The microsporidia reported as pathogens in humans include Encephalitozoon cuniculi, Encephalitozoon hellem, Encephalitozoon intestinalis, Enterocytozoon bieneusi, Trachipleistophora hominis, Trachipleistophora anthropophthera, Pleistophora species, P. ronneafiei, Vittaforma corneae, Microsporidium sp, Nosema ocularum, Anncaliia connori, Anncaliia vesicularum, and Anncaliia algerae. The greatest risk of disease occurs among patients with a CD4+ <100 cells/µL	Clinical syndromes can vary by infecting species. The most common manifestation is diarrhea. E. bieneusi is associated with malabsorption, diarrhea, and cholangitis. E. cuniculi is associated with hepatitis, encephalitis, and disseminated disease. E. intestinalis is associated with diarrhea, disseminated infection, and superficial keratoconjunctivitis. E. hellem is associated with superficial keratoconjunctivitis, sinusitis, respiratory disease, prostatic abscesses, and disseminated infection. Anncaliia and Trachipleistophora are associated with keratoconjunctivitis. Nosema, Vittaforma, and Microsporidium are associated with stromal keratitis following trauma in immunocompetent hosts. Pleistophora, Anncaliia, and Trachipleistophora are associated with myositis. Trachipleistophora is associated with encephalitis and disseminated disease.	Examination of 3 stool samples with chromotrope and chemofluorescent stains	Patients who have CD4 counts <200 cells/µL should avoid untreated water sources. No specific chemoprophylactic regimens are known to be effective in preventing microsporidiosis.	Initiate or optimize ART with immune restoration to CD4 count >100 cells/mm3 Severe dehydration, malnutrition, and wasting should be managed by fluid support and nutritional supplements
Table adapted from Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents