Common Manifestations Associated With HIV Infection by Organ System

Common Manifestations Associated With HIV Infection by Organ System
Syndrome	Cause	Diagnostic Evaluation	Treatment*	Symptoms/Comments
Cardiac
Cardiomyopathy	Direct viral damage to cardiac myocytes	Echocardiography	ART	Symptoms of heart failure
Gastrointestinal
Esophagitis	Candidiasis, CMV, or HSV	Upper endoscopy (esophagoscopy) with biopsy of ulcers	Treatment of underlying cause with antimicrobials	Dysphagia, anorexia
Gastroenteritis or colitis	Nontyphoidal Salmonella infections, MAC, Cryptosporidium (cryptosporidiosis), Cyclospora (cyclosporiasis), CMV, microsporidia, Cystoisospora (Isospora) belli (cystoisosporiasis), or Clostridioides difficile	Stool culture Stool staining Lower gastrointestinal endoscopy with biopsy	Treatment of cause: Antibiotics for Salmonella, MAC, and C. difficile Antimicrobials for Cystoisospora, Cyclospora, and microsporidia Antiviral medications for CMV	Diarrhea, weight loss, abdominal cramping
Cholecystitis or cholangitis	CMV, Cryptosporidium, Cyclospora, or microsporidia	Ultrasonography Hepatobiliary iminodiacetic acid scan (HIDA) Magnetic resonance cholangiopancreatography (MRCP) Endoscopy	Antiviral medications for CMV Antimicrobials for Cryptosporidium, Cyclospora, and microsporidia	Possibly pain or obstruction
Rectal and perirectal lesions	Proctitis caused by Neisseria gonorrhoeae or Chlamydia trachomatis (particularly LGV), HSV, syphilis	Physical examination Biopsy Gram staining and culture of rectal discharge or tissue NAAT of rectal discharge Rapid plasma reagin (RPR)/treponemal antibody test measured in serum	Treatment of underlying cause	High incidence in women and men who have sex with men via anal receptive sexual intercourse†
Hepatocellular damage due to hepatitis viruses, opportunistic infections, or antiviral drug toxicity	TB, MAC, CMV, or peliosis hepatis (bartonellosis) Chronic hepatitis B or chronic hepatitis C, which may be worsened by HIV infection	Differentiation from hepatitis due to ART or other medications Liver biopsy sometimes necessary	Treatment of underlying cause	Symptoms of hepatitis (eg, anorexia, nausea, vomiting, jaundice)
Genital/Reproductive
Anal and external genital lesions	HSV Genital warts or anal or cervical cancer induced by HPV Mpox virus	Examination Gram staining and culture of perianal or genital discharge NAAT Biopsy	Treatment of underlying cause	High incidence in women and men who have sex with men via anal receptive sexual intercourse†
Pelvic inflammatory disease	Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, or other usual pathogens	See Diagnosis of Pelvic Inflammatory Disease	See Treatment of Pelvic Inflammatory Disease	Possibly increased in severity, atypical presentation, and more difficult to treat in women with HIV infection
Vulvovaginal candidiasis	Candida species	See Diagnosis of Candidal Vaginitis	See Treatment of Candidal Vaginitis	Possibly increased in severity or recurrence in women with HIV infection
Hematologic
Anemia	Multifactorial: HIV-induced bone marrow suppression Immune-mediated peripheral destruction Anemia of chronic disease Infections, particularly human parvovirus B-19, disseminated MAC, or histoplasmosis Cancers	See Evaluation of Anemia For parvovirus B19 infection, bone marrow examination (to check for multinucleated erythroblasts) or serum or bone marrow PCR testing	Treatment of underlying cause Transfusion as needed Erythropoietin for anemia due to antineoplastic medications or zidovudine if severity warrants transfusion and serum erythropoietin level is < 500 mU/L IVIG for parvovirus	With parvovirus, sometimes acute severe anemia
Thrombocytopenia	Immune thrombocytopenia, drug toxicity, HIV-induced bone marrow suppression, immune-mediated peripheral destruction, infections, or cancer	CBC, clotting tests (eg, PT/INR, aPTT), peripheral smear, bone marrow biopsy, or von Willebrand factor measurement	ART IVIG for treatment of bleeding or preoperatively as prophylaxis Possibly anti-Rho(D) IgG, vincristine, danazol, or interferon If severe and intractable, splenectomy	Often asymptomatic and may occur in patients with otherwise asymptomatic HIV infection
Neutropenia	HIV-induced bone marrow suppression, immune-mediated peripheral destruction, infections, cancer, or drug toxicity	See Diagnosis of Neutropenia	For severe neutropenia (< 500/mcL [< 0.5 × 10⁹/L]) plus fever, immediate broad-spectrum antibiotics If drug-induced, granulocyte or granulocyte-macrophage colony-stimulating factors	Fever
Neurologic
HIV-associated neurocognitive disorder (HAND), including HIV-associated dementia	Direct virus-induced brain damage and neuroinflammation (astrocytes, microglia)	HIV RNA level in CSF CT or MRI to evaluate for brain atrophy (nonspecific)	ART, which may reverse damage and improve function, but low levels of cognitive dysfunction commonly persist, even in treated patients	Often presenting with mild to severe cognitive impairment with or without motor deficits Progression to dementia uncommon in treated patients
Ascending paralysis	Guillain-Barré syndrome or CMV polyradiculopathy	Spinal cord MRI CSF testing	Treatment of CMV polyradiculopathy Supportive care for Guillain-Barré syndrome	Neutrophilic pleocytosis in patients with CMV polyradiculopathy, possibly simulating bacterial meningitis
Acute or subacute focal encephalitis	Toxoplasma gondii (toxoplasmosis)	CT or MRI to check for ring-enhancing lesions, especially in basal ganglia Antibody testing of CSF (sensitive but not specific) PCR testing to evaluate for T. gondii DNA in CSF Brain biopsy (rarely indicated)	Pyrimethamine, folinic acid, sulfadiazine, and possibly TMP/SMX Cotrimoxazole (clindamycin if allergic to sulfa medications—see Toxoplasmosis: Treatment of immunocompromised patients)	Primary prophylaxis with TMP/SMX Cotrimoxazole (as for Pneumocystis pneumonia) indicated for patients with a CD4 count of < 100 cells/mcL and previous toxoplasmosis or positive antibodies; can be stopped if CD4 counts increase to > 200 cells/mcL for ≥ 3 months in response to ART
Subacute encephalitis	CMV Less often, HSV or VSV	CSF PCR testing Response to treatment	Antiviral medications	With CMV, often delirium, cranial nerve palsies, myoclonus, seizures, and progressively impaired consciousness at presentation Often responds rapidly to treatment
Myelitis or polyradiculopathy	CMV	Spinal cord MRI CSF PCR testing	Antiviral medications	Simulates Guillain-Barré syndrome
Progressive encephalitis of white matter only	Progressive multifocal leukoencephalopathy due to reactivation of latent JC virus infection	Brain MRI CSF testing	ART to reverse the immunodeficiency (no medications are effective for JC virus)	Usually fatal within a few months May respond to antiretroviral medications
Subacute meningitis	Coccidioidomycosis, Cryptococcus (cryptococcosis), Histoplasma (histoplasmosis), or Mycobacterium tuberculosis	CT or MRI CSF stains, antigen tests, PCR testing, and cultures	Treatment of underlying cause	Outcomes improved by early treatment
Peripheral neuropathy	Direct effects of HIV or CMV infection or antiviral drug toxicity	History Sensory and motor testing	Treatment of underlying cause or withdrawal of toxic drugs	Very common Not quickly reversible
Ophthalmologic
Retinitis	CMV or VZV	Direct retinoscopy	Specific anti-CMV or anti-VZV medications	Requires examination by specialist VZV causes acute retinal necrosis in some patients with advanced HIV infection
Oral
Oral candidiasis	Immunosuppression by HIV	Physical examination	Systemic antifungals	Possibly painless in early stages
Mpox	Mpox virus	Physical examination PCR testing of fluid from vesicles	Antiviral medications	Painful, vesicular rash can begin in mouth then spread High incidence in men who have sex with men†
Intraoral ulcers	HSV or aphthous stomatitis	Physical examination	For aphthous ulcers, intralesional or systemic glucocorticoids and systemic montelukast and thalidomide For herpes, acyclovir	May be severe and result in undernutrition
Periodontal disease	Mixed oral bacterial flora	Physical examination	Improved hygiene and nutrition Antibiotics	May be severe, with bleeding, swelling, and tooth loss
Painless intraoral mass	Kaposi sarcoma, lymphoma, or tumors induced by HPV	Biopsy	Treatment of mass	—
Painless white filiform patches on the sides of the tongue (oral hairy leukoplakia)	Epstein-Barr virus (EBV)	Physical examination	Acyclovir	Usually asymptomatic
Pulmonary
Subacute (occasionally acute) pneumonia	Mycobacteria Fungi such as P. jirovecii, C. neoformans, H. capsulatum, Coccidioides immitis, or aspergillosis	Pulse oximetry Chest radiography Tuberculosis skin tests (sometimes false-negative because of anergy) Bronchoscopy with special stains and cultures of bronchial lavage specimens sometimes necessary	Treatment of underlying cause	Possibly cough, tachypnea, and chest discomfort at presentation Mild hypoxia or increased alveolar-arterial oxygen gradient possibly occurring before evidence of pneumonia on radiography
Acute (occasionally subacute) pneumonia	Typical bacterial pathogens or bacteria from the Haemophilus, Pseudomonas, Nocardia, or Rhodococcus genus	In patients with known or suspected HIV infection and pneumonia, exclusion of opportunistic or unusual pathogens	Treatment of underlying cause	Possibly cough, tachypnea, and chest discomfort at presentation
Tracheobronchitis	Candida species or HSV	Bronchoscopy with special stains and cultures of bronchial lavage specimens	Treatment of underlying cause	Possibly cough, tachypnea, and chest discomfort at presentation
Subacute or chronic pneumonia or mediastinal adenopathy	Kaposi sarcoma or B-cell lymphoma	Chest CT Bronchoscopy	Treatment of underlying cause	Possibly cough, tachypnea, and chest discomfort at presentation
Renal
Nephrotic syndrome or renal insufficiency	Direct viral damage, resulting in focal glomerulosclerosis	Kidney biopsy	ART or ACE inhibitors possibly useful	Increased incidence in African Americans and in patients with a low CD4 count
Tubular dysfunction (glucosuria, proteinuria)	Some antiviral medications	Urinalysis and/or blood tests	Dose reduction or discontinuation of the antiviral medication	—
Dermatologic
Dermatomal painful vesicular eruption	VZV	History and physical examination PCR-based testing DNA testing on scrapings from vesicular skin lesions that have not yet crusted Culture (best if done on unroofed and recently ruptured vesicles)	Acyclovir or related medications	Common Possible prodrome of mild to severe pain or tingling before skin lesions appear PCR-based testing is most sensitive
Painful mucocutaneous ulcers or grouped vesicles (genital/oral)	HSV	History and physical examination PCR-based testing of ulcer HSV culture of ulcer	Antiviral medications if lesions are severe, extensive, persistent, or disseminated	Atypical lesions of herpes simplex are extensive, severe, or persistent PCR-based testing is most sensitive
Scabies	Sarcoptes scabiei	History and physical examination and scrapings	See Treatment of Scabies	Possibly severe hyperkeratotic lesions
Generalized painful vesiculopustular rash with lymphadenopathy	Mpox virus	Physical examination PCR testing of fluid from vesicles, pustules, and/or dry crusts	Antiviral medications	Rash can spread Lymphadenopathy is common
Violaceous or red papules or nodules	Kaposi sarcoma or bartonellosis	Biopsy	ART and treatment of cause	—
Centrally umbilicated skin lesions	Cryptococcosis or molluscum contagiosum	See Diagnosis of Molluscum Contagiosum and Diagnosis of Cryptococcosis	See Treatment of Cryptococcosis and Treatment of Molluscum Contagiosum	May be the presenting sign of cryptococcemia or molluscum contagiosum
Systemic
Sepsis and septic shock due to nosocomial gram-negative bacillary and staphylococcal infections, disseminated opportunistic infections	Gram-negative bacilli, Staphylococcus aureus, Candida species, Salmonella, MAC, or H. capsulatum	Blood cultures Bone marrow examination	Treatment of underlying cause	—
Wasting syndrome (substantial weight loss)	Multifactorial, including conditions associated with advanced HIV-related illness‡ (eg, opportunistic infections, cancers, hypogonadism)	Defined as weight loss of > 10% of body weight	ART (the primary treatment for this syndrome) Treatment of underlying infections; treatment of HIV-related hypogonadism when indicated Measures to improve appetite and caloric intake	—
* ART is always part of the treatment plan. Medications are listed in this treatment section only when there is no more specific treatment.
† These diagnoses are surrogates of behaviors that increase the risk of HIV infection; when present, these diagnoses should prompt HIV testing.
‡ Formerly called acquired immune deficiency syndrome (AIDS).
aPTT = activated partial thromboplastin time; ART = antiretroviral therapy; CBC = complete blood count; CMV = cytomegalovirus; CSF = cerebrospinal fluid; HPV = human papillomavirus; HSV = herpes simplex virus; IVIG = IV immune globulin; LGV = lymphogranuloma venereum; MAC = Mycobacterium avium complex; Mpox = monkeypox; NAAT = nucleic acid amplification testing; PCR = polymerase chain reaction; PT/INR = prothrombin time/international normalized ratio; PTT = partial thromboplastin time; TMP/SMX = trimethoprim/sulfamethoxazole; VZV = varicella-zoster virus.

* ART is always part of the treatment plan. Medications are listed in this treatment section only when there is no more specific treatment.

† These diagnoses are surrogates of behaviors that increase the risk of HIV infection; when present, these diagnoses should prompt HIV testing.

‡ Formerly called acquired immune deficiency syndrome (AIDS).

aPTT = activated partial thromboplastin time; ART = antiretroviral therapy; CBC = complete blood count; CMV = cytomegalovirus; CSF = cerebrospinal fluid; HPV = human papillomavirus; HSV = herpes simplex virus; IVIG = IV immune globulin; LGV = lymphogranuloma venereum; MAC = Mycobacterium avium complex; Mpox = monkeypox; NAAT = nucleic acid amplification testing; PCR = polymerase chain reaction; PT/INR = prothrombin time/international normalized ratio; PTT = partial thromboplastin time; TMP/SMX = trimethoprim/sulfamethoxazole; VZV = varicella-zoster virus.

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Human Immunodeficiency Virus (HIV) Infection