Summary![toggle arrow icon](https://manus-media.amboss.com/icons/chevron_up.svg)
As HIV infection progresses, immune function declines, and affected individuals become increasingly vulnerable to opportunistic infections and certain malignancies. Some of these conditions are typically seen when CD4 counts are less than 200 cells/μL; these are known as AIDS-defining conditions. With early detection of HIV infection and widespread use of antiretroviral therapy (ART), many of these conditions have become less common and more treatable. Patients with HIV are now more likely to develop non-HIV-associated conditions or complications of ART, such as immune reconstitution inflammatory syndrome (IRIS), hepatotoxicity, or nephrotoxicity. However, even patients with well-controlled HIV remain at increased risk of some communicable and noncommunicable diseases, and the presentation of these conditions may be atypical. This article provides a system-based overview of HIV-associated conditions and their management.
See also “Kaposi sarcoma,” “Progressive multifocal leukoencephalopathy,” “Bacillary angiomatosis,” and “Mycobacterium avium complex infections.”
AIDS-defining conditions![toggle arrow icon](https://manus-media.amboss.com/icons/chevron_up.svg)
Overview [1]
- AIDS-defining conditions are a set of potentially life-threatening conditions that indicate the progression of HIV infection to AIDS
-
As the CD4 count declines, the immune system is weakened and many pathological processes may occur, such as:
- Development of malignancies e.g., non-Hodgkin lymphomas
- Rapid spread of opportunistic and nonopportunistic bacterial and fungal infections (e.g., coccidioidomycosis, pneumocystis pneumonia, mycobacterial infections)
- Reactivation of latent infections (e.g., tuberculosis, herpes simplex infections, shingles)
- AIDS; (also known as advanced HIV) is defined as the development of an AIDS-defining condition or a CD4 count of < 200 cells/μL in HIV-infected patients. [2]
AIDS-defining conditions [1][3] | |
---|---|
CD4 count (in cells/μL) | Conditions |
Variable |
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< 250 |
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< 200 |
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< 150 |
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< 100 |
|
< 50 |
|
Some AIDS-defining conditions are opportunistic infections, but the terms are not interchangeable!
Management [3]
- Optimize antiretroviral therapy (most effective measure).
- Treat AIDS-defining condition (see relevant sections below for details).
- Prevent further opportunistic infections.
- See “Primary prevention of opportunistic infections in HIV” and “Vaccinations in HIV-infected individuals.”
- Avoid pathogen exposure.
Adequate HIV treatment (ART) is key to minimizing the risk of opportunistic infections.
Neurological complications![toggle arrow icon](https://manus-media.amboss.com/icons/chevron_up.svg)
The most common causes of focal neurological deficits in patients with advanced HIV or AIDS are cerebral toxoplasmosis, primary CNS lymphoma, and progressive multifocal leukoencephalopathy. [3]
Overview
Differential diagnosis of CNS lesions in HIV-positive patients with CD4 count < 200 | ||||
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Condition | Description | Clinical features | Diagnostics | Treatment |
Cerebral toxoplasmosis [3][12] |
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Primary CNS lymphoma (PCNSL) [14][15] |
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Cerebral abscess (bacterial) [17][18][19][20] |
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HIV-associated neurocognitive disorder (HAND)
- Definition: neurocognitive impairment in patients with HIV that cannot be attributed to a cause other than HIV infection
- Etiology: : thought to result from a combination of dissemination of HIV into the CNS and the resultant immune activation [8]
- Epidemiology: common even in patients with well-controlled HIV (affecting up to 50% of individuals) [9]
-
Clinical features [9]
- Early: mild impairment in attention, recall, and executive function
- Advanced: HIV-associated dementia (considered an AIDS-defining condition)
- Subcortical dementia: memory loss, depression, movement disorders, behavioral changes (e.g., apathy)
- Severe neurologic deficits: altered mental state, aphasia, gait disturbances [23]
- More common in patients with advanced or untreated HIV [8][24]
- Due to effectiveness of HAART, elderly HIV patients more commonly develop non-HIV dementia such as Alzheimer disease than HIV-associated dementia.
-
Diagnostics [18][25]
- Cognitive and neuropsychological tests [9]
-
Assess at least 5 cognitive domains: attention, language, memory, simple and complex motor skills, sensory-perceptual skills, and higher executive functioning
- HAND: mild cognitive impairment (1 SD below mean) in ≥ 2 domains
- HIV-associated dementia: significant cognitive impairment (2 SDs below mean) in ≥ 2 domains
-
Assess at least 5 cognitive domains: attention, language, memory, simple and complex motor skills, sensory-perceptual skills, and higher executive functioning
- Imaging: CT or MRI brain without and with IV contrast
- Diffuse cerebral atrophy; disproportionate to the patient's age
- Patchy symmetrical changes in the periventricular and deep white matter
- No mass effect, no contrast-enhancement
- Additional evaluation
- Rule out other causes of dementia (e.g., normal B12, folate, and TSH levels, negative syphilis).
-
Brain biopsy [23]
- Performed only if there is diagnostic uncertainty
- Histopathology shows giant cells with multiple nuclei (formed through fusion of HIV-infected monocytes).
- Cognitive and neuropsychological tests [9]
- Treatment: antiretroviral therapy (but avoid efavirenz) [26][27]
HAND is typically a diagnosis of exclusion.
Avoid efavirenz in patients with suspected or confirmed HIV-associated neurocognitive disorder as it may worsen cognitive impairment.
HIV-associated distal symmetric polyneuropathy (HIV–DSPN) [28]
- Definition: axonal peripheral neuropathy in individuals with HIV that cannot be attributed to a cause other than HIV infection
- Etiology: damage to the nervous system by HIV or ART medications
- Risk factors
-
Clinical features
- Numbness, tingling, and pain in stocking-glove distribution
- Decreased pinprick and vibration sensation involving distal lower extremities
- Decreased/absent ankle jerk reflex
- Proximal spread of symptoms suggests HIV-DSPN progression
-
Diagnostics
- Laboratory testing to rule out non-HIV-related causes (e.g., basic metabolic panel, HbA1c)
- Typical clinical presentation and exclusion of other causes of peripheral neuropathy are sufficient for diagnosis.
-
Treatment
- Management of reversible risk factors (e.g., initiate ART in untreated patients with HIV, optimize management in patients with diabetes mellitus)
- Symptomatic pain management
- Anticonvulsants (e.g., gabapentin, pregabalin, lamotrigine) are the preferred medication
- Topical capsaicin patches
- Antidepressants (e.g., duloxetine, amitriptyline) are preferred in patients with depression
- NSAIDs, acetaminophen, opioids
Other [18][29]
- Infectious
-
Noninfectious
- Cerebrovascular events due to: [30]
- Opportunistic infections (e.g., TB meningitis, VZV vasculitis)
- HIV-associated vasculopathy and coagulopathy
- Metabolic encephalopathy [31]
- Dementia: See “HIV-associated neurocognitive disorder.”
- Cerebrovascular events due to: [30]
Approach to undifferentiated neurological symptoms in patients with HIV![toggle arrow icon](https://manus-media.amboss.com/icons/chevron_up.svg)
General principles [3][29]
Patients with HIV can present with neurologic problems at any stage of infection.
-
Well-controlled HIV
- Consider non-HIV associated conditions, such as stroke, brain tumors, and age-related neurodegenerative illnesses.
- Mild neurocognitive impairment is common even in well-controlled HIV (see “HIV-associated neurocognitive disorder”).
- The diagnostic workup for this group of patients is similar to that for individuals who do not have HIV.
- CD4 counts < 200: Suspect opportunistic infections and AIDS-related cancers of the CNS.
Diagnostics
The following is applicable to patients with suspected opportunistic infections or AIDS-related CNS tumors. [3]
-
Laboratory studies: should be guided by the pretest probability of the diagnoses under consideration
- CD4 count and viral load
- CBC, ESR, and blood cultures
- Relevant serology: T. gondii IgG, cryptococcal Ag
- Syphilis screening
-
Neuroimaging (CT or MRI brain with contrast) is indicated in all patients to assess for [31]
- Space-occupying lesions
- Evidence of ↑ ICP (mass effect)
- Cerebral edema
-
Lumbar puncture (unless there are contraindications for lumbar puncture)
- Indicated for most suspected opportunistic infections (except brain abscess)
-
CSF analysis should include:
- Flow cytometry for primary CNS lymphoma
- CSF-VDRL
- Cryptococcal antigen testing
- PCR for T. gondii, M. tuberculosis, EBV, JC virus, HSV
- Cell count, culture, cytology
- See also “CSF analysis in meningitis” and “CSF analysis in meningitis due to atypical pathogens.”
- Brain biopsy: Consider only if needed for a definitive diagnosis after assessing the risks and benefits of the procedure.
Management
- Treat the underlying cause.
- Seizures: Anticonvulsants should be initiated and continued for the duration of acute treatment.
-
Management of ↑ ICP [3]
- Impending herniation
- Confirmed histological diagnosis
- Oral/IV corticosteroids (e.g., dexamethasone ) [3][32]
- Discontinue corticosteroids as early as feasible.
- Before confirmation of diagnosis: Consider mannitol (see “Hyperosmolar therapies in ICP management”). [33]
- Confirmed histological diagnosis
- Stable patients without impending herniation: Consider empiric treatment for cerebral toxoplasmosis.
- Inadequate improvement on empiric treatment: Consider brain biopsy for a definitive diagnosis.
- Clinical and radiological improvement on empiric treatment for 2 weeks: Continue treatment.
- Impending herniation
Avoid administering corticosteroids before diagnostic confirmation, as corticosteroids alter neuroimaging and biopsy findings and may delay a diagnosis of PCNSL. [15]
Ophthalmologic complications![toggle arrow icon](https://manus-media.amboss.com/icons/chevron_up.svg)
Ocular complications in HIV are important to recognize because of the potential risk of vision loss. Consult ophthalmology in all patients with HIV who have ocular symptoms or abnormal findings on examination.
Differential diagnosis of ophthalmologic presentations in HIV-positive patients | ||
---|---|---|
Clinical presentation | Painless | Painful |
Vision loss |
|
|
No vision loss |
|
Ophthalmologic complications of HIV [34][35] | |||
---|---|---|---|
CD4 count (in cells/μL) | Condition | Clinical features | Treatment |
Variable | HIV retinopathy [36] |
|
|
Herpes simplex keratitis [37] |
|
| |
[3][38][39] |
|
| |
Varicella-zoster retinitis (acute retinal necrosis and progressive outer retinal necrosis. [3][38][41] |
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< 100 | Toxoplasmosis retinochoroiditis [42][43][44] |
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< 50 | Cytomegalovirus retinitis [3][46] |
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Cardiovascular complications![toggle arrow icon](https://manus-media.amboss.com/icons/chevron_up.svg)
General principles
- Cardiovascular abnormalities in patients with HIV include:
- Complications related to advanced disease (e.g., opportunistic infections, malignancy)
- Complications that can arise from ART or chronic inflammation related to HIV
- The clinical presentation of and diagnostic approach to cardiovascular conditions are the same as in patients without HIV.
HIV-associated atherosclerotic cardiovascular disease (ASCVD) [47][48]
People living with HIV are at an increased risk of ASCVD compared to uninfected individuals. [47]
- Etiology: chronic inflammation (e.g., due to HIV infection, protease inhibitors) [49]
-
Risk assessment [48]
- Perform ASCVD risk assessment if indications are met.
- Reassess ASCVD risk annually.
- Consider adjusting the risk score upward by 1.5–2 times if any of the following are present:
- Low CD4 count (< 350)
- Delayed initiation of ART
- Lack of response or nonadherence to HIV treatment
- Fatty liver disease, lipodystrophy, or metabolic syndrome
- Coinfection with hepatitis C
-
Management [48]
- Primary and secondary preventive measures (see “ASCVD prevention” for details).
- In patients requiring statin therapy (i.e., known CAD or high-risk of ASCVD):
- Statins with a low (e.g., pitavastatin ) or moderate (e.g., atorvastatin , rosuvastatin ) likelihood of interacting with ART are preferable.
- Start at a low dose and gradually increase as needed.
- Discontinue or decrease the dose of statins in consultations with a specialist if adverse effects develop.
- Initiate ART early.
- There is no evidence to support avoiding protease inhibitors.
HIV-associated cardiomyopathy [50]
- Etiology: thought to be multifactorial, including drug-induced, metabolic, or HIV-induced myocardial damage
-
Clinical features
- Can manifest with symptoms of heart failure
- Patients may be asymptomatic or minimally symptomatic
- Diagnosis: echocardiogram showing reduced LVEF, LV diastolic dysfunction, or LV dilation
-
Management
- Correct the underlying cause.
- Guideline-directed medical therapy for heart failure
- Patients with HIV-1 may benefit from IV immunoglobulin (limited data).
- Initiate ART.
Miscellaneous [49][51]
- Pericardial effusion
- Cardiac tumors
- Vasculitis [52]
- Pulmonary artery hypertension
- Endocarditis
Pulmonary complications![toggle arrow icon](https://manus-media.amboss.com/icons/chevron_up.svg)
Reactivation tuberculosis [3]
-
Epidemiology [3]
- In patients with HIV, tuberculosis (TB) is the leading cause of morbidity and mortality worldwide.
- Typically occurs at CD4 counts < 400.
-
Clinical features: Active TB may be subclinical or asymptomatic in patients with HIV.
- CD4 count > 200: The presentation is similar to that of HIV-negative patients (e.g., cough, fever, weight loss, night sweats).
-
CD4 count < 200
- May present with a rapidly progressive illness with features of sepsis, including high fever
- Higher risk of extrapulmonary or disseminated TB
- Diagnostics: similar to that of HIV-negative patients (see “Diagnostics” in “Tuberculosis”)
Diagnosing TB in patients with HIV [3] | ||
---|---|---|
Indications for testing | Recommended studies | |
Latent TB infection (LTBI) | ||
Active TB disease |
|
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Treatment
- Start empiric treatment in patients with advanced HIV with clinical and radiographic features that suggest active TB (see “Tuberculosis” for details and dosages).
- Indications for treating as LTBI
- Positive screening tests without signs of active infection
- Close contact with a person with infectious TB, regardless of the results of screening tests
- Initiate ART
- Within 2 weeks of starting TB therapy if CD4 count is < 50 and within 8 weeks in patients with higher CD4 counts
- ART regimens may need to be altered to minimize drug interactions.
- Monitor for IRIS in patients with CD4 counts < 100.
All patients should be screened for latent TB at the time of HIV diagnosis and at regular intervals thereafter based on individual risk factors.
In asymptomatic patients with a positive IGRA or TST, a normal chest x-ray is sufficient to rule out active TB in nonendemic areas like the US. [3]
In patients with advanced HIV, start immediate empiric treatment if suspicion for TB is high!
Pneumocystis jirovecii pneumonia (PCP) [3]
Pneumocystis jirovecii is a ubiquitous fungus that can cause pneumonia in patients with AIDS, especially those with CD4 counts < 200. The incidence has declined since the introduction of ART and the use of prophylaxis.
-
Clinical features
- Subacute onset (e.g., 3–4 weeks) of fever, nonproductive cough, dyspnea, and chest pain
- Spontaneous pneumothorax
- Fulminant pneumonia is uncommon in patients with HIV.
-
Management: Same as for HIV-negative patients; see “Pneumocystis pneumonia.”
- Characteristic diagnostic findings
- ↑ Beta-D-glucan
- CXR: diffuse bilateral infiltrates (ground-glass appearance)
- Treatment of choice: trimethoprim/sulfamethoxazole (TMP/SMX) with or without glucocorticoids
- Special considerations in HIV
- Start ART (if not yet initiated) within 2 weeks of PCP diagnosis.
- Monitor for adverse events caused by TMP-SMX.
- Characteristic diagnostic findings
- PCP prophylaxis: See “Primary prevention of opportunistic infections in HIV.”
Community-acquired pneumonia [3]
- Common; particularly at CD4 counts < 100
- Recurrent pneumonia (≥ 2 episodes within 1 year) is an AIDS-defining illness.
- Causative pathogens
- Common: Streptococcus pneumoniae and Haemophilus influenzae
- Less common: Mycoplasma pneumonia, Chlamydia spp., and Staphylococcus aureus
- Clinical features, diagnostics, and treatment are the same as for HIV-negative patients; see “Pneumonia” for further details.
- Prevention: pneumococcal vaccine and inactivated influenza vaccine are recommended; see “Immunization schedule for adults” for details.
- In patients not already on ART, initiate treatment as soon as possible.
Miscellaneous
-
Infectious [3]
- Viral pneumonia (including CMV pneumonia and influenza)
- Mycobacterium avium complex infection
- Fungal infections, including coccidioidomycosis and histoplasmosis (see “Systemic fungal infections”)
- Parasitic infections, including toxoplasmosis and strongyloidiasis
- Invasive aspergillosis (infrequent with CD4 count < 50) [54]
-
Noninfectious complications [55]
- COPD
- Asthma [56]
- Lymphocytic interstitial pneumonitis [57]
- Malignancy
- Sarcoidosis [58]
Gastrointestinal complications![toggle arrow icon](https://manus-media.amboss.com/icons/chevron_up.svg)
General principles
- GI symptoms are common in HIV and can occur at any CD4 count.
- Patients with well-controlled HIV are more likely to be experiencing common GI problems (i.e., similar to individuals without HIV).
- Opportunistic infections, malignancy, and HIV wasting syndrome are typically seen in patients with advanced immunosuppression.
Dyspepsia, dysphagia, and odynophagia [59][60]
-
Etiology
- Advanced HIV: opportunistic infections (e.g., Candida, CMV, HSV, MAC) or malignancy (e.g., Kaposi sarcoma)
- Well-controlled HIV: Consider other causes (e.g., GERD); see “Etiologies of esophagitis” for details.
- Odynophagia: esophagitis or painful oropharyngeal lesions (see “Mucosal and mucocutaneous complications in HIV infection”)
-
Management
- Start ART (if not already initiated).
-
Mild dysphagia/odynophagia: Diagnostic studies are not routinely required; consider a trial of empiric therapy.
- Advanced HIV: trial of fluconazole for at least 2 weeks after resolution of symptoms.
- Well-controlled HIV: trial of acid suppression therapy with PPIs for 8 weeks
- Moderate to severe dysphagia/odynophagia or failure of empiric therapy: endoscopy for examination of mucosa and biopsy
- Characteristic findings in advanced HIV: See “Infectious esophagitis.” [61]
- Characteristic findings in well-controlled HIV: See “Initial diagnostics” in “Esophagitis.”
- Targeted treatment depends on the underlying etiology: See “Infectious esophagitis” for details and dosages.
Inadequate response to empiric treatment should prompt further evaluation for other causes (e.g., HSV esophagitis).
Diarrhea [60]
Diarrhea is the most common GI complaint in patients with HIV and may occur at any CD4 count.
-
Etiology
- Infectious (common in advanced HIV): e.g., MAC, cryptosporidiosis, cystoisosporiasis, CMV
- Malignancy: e.g., lymphoma, Kaposi sarcoma
- Idiopathic: e.g., HIV enteropathy
- Medication-related (particularly protease inhibitors)
-
Diagnostics [60]
- Stool analysis for infectious organisms
- Consider blood culture for suspected MAC infection.
- Upper and lower GI endoscopy with biopsy for patients with:
- Negative stool tests
- Suspected noninfectious etiology
-
Treatment
- Infectious diarrhea: directed antimicrobial therapy
- ART-related diarrhea: Consider an alternative ART regimen, if possible.
-
Chronic diarrhea secondary to HIV enteropathy [62]
- Symptomatic management e.g., oral rehydration, antidiarrheal agents
- Low-fat, lactose-free diet
- Refractory cases: Consider antisecretory agents, e.g., octreotide, in consultation with a specialist. [63]
CMV colitis manifests as abdominal pain and bloody diarrhea. CMV esophagitis can manifest as odynophagia. Linear ulcers on endoscopy and intracellular inclusions (owl's eye appearance) on histology are characteristic diagnostic findings of CMV infection. [64]
HIV wasting syndrome [65][66]
- CD4 count: variable (typically seen in advanced HIV)
- Clinical features: unintentional weight loss of ≥ 10% and any of the following for ≥ 30 days
-
Management
- Optimize nutrition (high-protein high-calorie diet).
- Antiemetics for nausea/vomiting
- Treat concurrent gastrointestinal infections (e.g., CMV colitis).
- Consider appetite stimulants: e.g., megestrol acetate or dronabinol
Protozoal infections
Cystoisosporiasis (isosporiasis) [3]
- Etiology: Cystoisospora, a protozoan, formerly known as Isospora
- Clinical features: > 1 month of watery diarrhea, abdominal pains, fever, weight loss; typically at CD4 counts < 200.
-
Management
- Trimethoprim/sulfamethoxazole
- Supportive care
- Prophylaxis: See “Primary prevention of opportunistic infections in HIV.”
Cryptosporidiosis [3]
- Etiology: Cryptosporidium species, most commonly C. hominis, C. parvum, or C. meleagridis
- Clinical features: chronic, watery diarrhea; (lasting > 1 month) with nausea and abdominal pains; typically at CD4 counts < 100
- Diagnostics: acid-fast cysts in stool
-
Treatment
- Symptomatic care: e.g., oral rehydration solution and antimotility agents
- Consider antiparasitic therapy (e.g., nitazoxanide ).
AIDS cholangiopathy [67]
- Etiology: opportunistic infections of the biliary tract (e.g., Cryptosporidium, CMV, microsporidia)
- Epidemiology: associated with advanced immunosuppression, often at a CD4 count < 100
- Clinical presentation: right upper quadrant pain with nausea, vomiting, and diarrhea
-
Diagnostics
-
Laboratory studies (may be normal in ∼ 25% of patients)
- Marked elevation of alkaline phosphatase and GGT
- Mild-moderate elevation of AST and ALT
- Normal or elevated bilirubin
- Imaging: most commonly ultrasound, but MRCP or ERCP may also be used
- Dilated common bile duct (CBD)
- Beaded appearance of the biliary tract may be seen.
- Intra- and extrahepatic ductal dilatation
- Cholangiography: stricture of the distal CBD
- Liver biopsy: consider if there is diagnostic uncertainty; findings resemble those of sclerosing cholangitis.
-
Laboratory studies (may be normal in ∼ 25% of patients)
-
Treatment
- Analgesics
- Management of acute cholangitis, if present, and opportunistic infections
- Initiate ART (if not already started).
- Consider ursodeoxycholic acid in patients with marked cholestasis.
- Consider endoscopic sphincterotomy for symptomatic relief.
Miscellaneous [68]
- Malignancy: including anal cancer due to HPV, lymphoma, and Kaposi sarcoma
-
Liver disease: Multiple etiologies can cause liver disease in HIV. [69]
- Hepatitis B or C coinfection
- CMV hepatitis
- Hepatotoxic effects of ART
- Nonalcoholic fatty liver disease
- Acute pancreatitis: most commonly due to medication use, although infections and hypertriglyceridemia may also be responsible [70]
Renal and genitourinary complications![toggle arrow icon](https://manus-media.amboss.com/icons/chevron_up.svg)
HIV-associated nephropathy [71][72]
- Definition: a type of collapsing focal segmental glomerulosclerosis that develops in patients with advanced HIV
- Risk factors: poorly controlled HIV, African descent [72]
- Pathophysiology: direct infection of glomerular and kidney tubular epithelial cells through HIV-1 [73]
- Clinical manifestations [72]
-
Diagnostics [74][75]
- Nephrotic range proteinuria (> 3 g in 24 hours)
- Elevated serum creatinine
- Kidney biopsy: collapsing FSGS, microcystic tubular dilatation, interstitial inflammation, and podocyte proliferation
-
Management [72]
- Initiate ART (if not already started).
- ACE inhibitors or ARBs (e.g., fosinopril) in consultation with nephrology and infectious disease specialists.
Miscellaneous [72][76][77]
- Chronic kidney disease
- Fluid and electrolyte disorders
- Nephrolithiasis
- Sexually transmitted infections (e.g., syphilis, HSV-2): See “Mucosal and mucocutaneous complications in HIV infection.”
- Proctitis (due to HIV or coinfection with e.g., gonorrhea, syphilis, chlamydia, or HSV) [78]
- Urinary tract infections
Hematological complications![toggle arrow icon](https://manus-media.amboss.com/icons/chevron_up.svg)
Anemia [79]
- Epidemiology: most common hematological abnormality in patients with advanced HIV
-
Etiology is multifactorial and includes;
- Hemolysis
- Infections (e.g., parvovirus B19, MAC)
- Medications: ART and drugs used to treat opportunistic infections (e.g., pyrimethamine, ganciclovir)
-
Diagnostics
- The diagnostic approach to anemia is similar to that of anemia in HIV-uninfected individuals.
- In addition, evaluate for opportunistic infections, especially in patients with advanced HIV and anemia. [68]
-
Management
- Severe or symptomatic anemia: Transfuse packed red blood cells as needed (see “Transfusion" for further information, including transfusion thresholds).
- Treat underlying reversible causes and infections.
- Prevention: ART reduces the incidence and degree of anemia.
HIV-associated thrombocytopenia [79]
- Epidemiology: Thrombocytopenia may be seen at any stage of the disease but is more common with increasing immunosuppression. [68]
- Etiology: immune-mediated destruction and ineffective thrombopoiesis
-
Diagnosis: HIV-associated thrombocytopenia is a diagnosis of exclusion.
- Rule out common secondary causes of thrombocytopenia, such as drugs, malignancy, infection.
- For further information, see “Diagnostics” in “Thrombocytopenia.”
-
Management
- Active hemorrhage: Consider platelet transfusion.
- Treat any secondary causes that may be present.
- Start ART (if not already initiated).
- Additional treatment is identical to that of immune thrombocytopenia: See “Treatment” in “Immune thrombocytopenia” for further information.
Unexplained thrombocytopenia may be the first manifestation of HIV and should prompt screening! [80]
Neutropenia [79]
-
Etiology
- Impaired hematopoiesis
- Drug-induced
- Particularly involving first-generation ARTs (especially zidovudine)
- Drugs used to treat opportunistic infections
-
Diagnosis
- Additional workup may not be required if the etiology is clear from history.
- Consider bone marrow biopsy in patients with atypical features : Megakaryocyte counts are decreased in HIV-associated neutropenia.
-
Management [79]
- Identify and treat reversible causes
- Start ART (if not already initiated).
- Severe neutropenia: Consider granulocyte colony-stimulating factor in consultation with specialists.
Miscellaneous [79]
Oncological complications![toggle arrow icon](https://manus-media.amboss.com/icons/chevron_up.svg)
Overview [81]
- Malignancy is more common at low CD4 counts
- Etiology is typically multifactorial.
- Immunosuppression
- Oncogenic viruses, e.g.:
- HHV8: Kaposi sarcoma, primary effusion lymphoma, multicentric Castleman disease
- EBV: primary CNS lymphoma, Burkitt lymphoma, immunoblastic lymphoma
- HPV: invasive cervical cancer, oral and pharyngeal cancers, penile, vulval, and anal cancer
- Hepatitis B and hepatitis C: hepatocellular carcinoma
- Chronic inflammation secondary to HIV infection itself
- Increased prevalence of carcinogenic risk factors, e.g., smoking
- Management [81][82]
Patients with HIV also develop incidental cancers (e.g., bowel, breast); encourage patients to attend all age-appropriate screening!
Early diagnosis and treatment of HIV with ART is the most important step in preventing HIV-associated malignancies.
AIDS-defining malignancies [1][81]
Include cancers that are associated with profound immunosuppression and are categorized as AIDS-defining illnesses
- Kaposi sarcoma
- Invasive cervical cancer
-
Non-Hodgkin lymphoma [83]
- Primary CNS lymphoma
- Burkitt lymphoma
- Immunoblastic lymphoma
- Other aggressive B-cell lymphomas (e.g., diffuse large B-cell lymphoma, plasmablastic lymphoma, primary effusion lymphoma, multicentric Castleman disease)
Non-AIDS-defining malignancies [81]
Include cancers that are found at higher rates among individuals with HIV but which are not classified as AIDS-defining conditions
- Hodgkin lymphoma [83]
- Lung cancer
- Hepatocellular carcinoma
- Head and neck carcinoma
- Vulvar cancer
- Penile cancer
- Anal cancer
Castleman disease [84]
A rare lymphoproliferative disorder that may affect one (unicentric) or multiple lymph nodes (multicentric).
- Clinical features: Multicentric Castleman disease (MCD) is more common in patients coinfected with HIV and HHV8.
-
Treatment of MCD (in consultation with a specialist) consists of ART in combination with:
- Rituximab-based regimen (can worsen coexisting Kaposi sarcoma)
- Antiviral therapy (IV ganciclovir or oral valganciclovir)
Rituximab can exacerbate Kaposi sarcoma.
Primary effusion lymphoma (PEL) [3][85]
PEL is a rare subtype of non-Hodgkin B-cell lymphoma most commonly seen in HIV-positive patients coinfected with HHV-8. Patients are also frequently coinfected with EBV.
- Clinical features: large effusions affecting the peritoneal, pleural, or pericardial spaces
- Treatment: ART in combination with chemotherapy (in consultation with a specialist) [3][86]
- Prognosis: generally poor
Rheumatological and musculoskeletal complications![toggle arrow icon](https://manus-media.amboss.com/icons/chevron_up.svg)
Differential diagnosis [87]
Differential diagnosis of joint pain in HIV | ||
---|---|---|
Presentation | Condition | |
Monoarthritis | No systemic features | |
Systemic features | ||
Polyarthritis | No systemic features | |
Systemic features |
Acute HIV infection can manifest with myalgias, arthralgias, and symmetrical viral polyarthritis.
HIV-specific rheumatological conditions [87]
HIV-specific rheumatological presentations [87][88] | |||
---|---|---|---|
Clinical features | Diagnosis | Management | |
HIV-associated arthritis |
|
|
|
Painful articular syndrome [89] |
|
|
|
Diffuse infiltrative lymphocytosis syndrome |
|
| |
Rheumatological manifestations of IRIS |
|
|
|
Impact of HIV and ART on other rheumatological disorders [87][88][89]
Impact of HIV and ART on rheumatological and musculoskeletal disorders | |
---|---|
Systemic lupus erythematosus [88] |
|
Rheumatoid arthritis (RA) [88] |
|
Psoriatic arthritis [89] |
|
Reactive arthritis [89] |
|
Osteoporosis [87] |
|
Avascular necrosis [88] |
|
Management [87][88]
- Management of chronic rheumatological disorders (e.g., SLE, RA) is similar to patients who are HIV-negative.
- In patients on ART with complete viral suppression and a CD4 count > 200, disease-modifying antirheumatic drugs (DMARDs) may be used safely when indicated (in consultation with specialists).
All HIV patients on immunosuppressive or immunomodulatory therapy like DMARD or glucocorticoids are at a high risk of developing opportunistic infections and should always receive prophylactic treatment (see “Primary prevention of opportunistic infections in HIV”)!
Dermatological complications![toggle arrow icon](https://manus-media.amboss.com/icons/chevron_up.svg)
Overview [90]
Dematological complications in patients who are HIV-positive are extremely common and may be infectious, inflammatory, neoplastic, or related to HIV treatment. These conditions may be atypical, severe, and refractory in patients with HIV.
Differential diagnosis of HIV-associated dermatologic conditions | ||
---|---|---|
Presentation | Conditions | |
Mucosal or mucocutaneous | Plaques | |
Vesicles/ulceration | ||
Papules | ||
Cutaneous | Patches or plaques | |
Vesicles/ulceration |
| |
Papules | ||
Pustules | ||
Purpura |
Mucosal and mucocutaneous manifestations
Mucosal and mucocutaneous complications in HIV infection [3][90][91] | |||
---|---|---|---|
Condition | Clinical features | Diagnostics | Treatment |
[3][92][93] |
|
|
|
|
| ||
Oral hairy leukoplakia |
|
| |
Mucocutaneous candidiasis [3] |
|
|
|
Herpes simplex infections [3][91] |
|
| |
Human papilloma virus [3][91] |
|
|
|
Syphilis [3][90][94] |
|
|
|
Recurrent aphthous ulcers [95] |
|
|
|
Kaposi sarcoma lesions resemble those of bacillary angiomatosis and histology is required to differentiate between the conditions.
Cutaneous manifestations
Cutaneous complications in HIV infection | |||
---|---|---|---|
Condition | Clinical features | Diagnosis | Treatment |
Varicella-zoster virus [3][91] |
|
|
|
Molluscum contagiosum [91][96] |
|
|
|
Scabies [90][91][97] |
|
| |
|
| ||
Psoriasis [98] |
|
|
|
Eosinophilic folliculitis [91][99] |
|
|
Miscellaneous [91]
- Bartonella infection (bacillary angiomatosis): erythematous papules and nodules
-
Cytomegalovirus:
- Perianal and oral ulcerations
- Macular purpura and leukocytoclastic vasculitis in the lower extremities,
- Verrucous keratotic lesions on the body
- M. tuberculosis: vesiculopapular rash that becomes necrotic in patients with miliary TB (rare) [100]
- MAC: papulonodular or hemorrhagic lesion on the extremities that may become necrotic
- Histoplasmosis: Papules, plaques, pustules, or ulcers [101]
- Cryptococcus: Erythematous papules, pustules, nodules, granulomatous, and/or verrucous lesions
-
Talaromycosis [102]
- Fungal infection typically seen in advanced HIV (CD4 count < 100) in patients who reside in or have traveled to endemic regions (South East Asia, southern China, or eastern India)
- Papules with central umbilication/necrosis (typical);pustules, nodules, and ulcers may also be seen.
Systemic fungal infections![toggle arrow icon](https://manus-media.amboss.com/icons/chevron_up.svg)
This section provides a brief overview of the management of common systemic fungal infections in patients with HIV. See “Systemic fungal infections” and “Yeasts” for further information on diagnostics and clinical features.
Overview of systemic fungal infections in patients with HIV [3] | |||
---|---|---|---|
Condition | CD4 count (in cells/μL) | Clinical and diagnostic features | Management |
Coccidioidomycosis |
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Histoplasmosis |
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|
Prevention of opportunistic infections![toggle arrow icon](https://manus-media.amboss.com/icons/chevron_up.svg)
Primary prevention [3]
To avoid the risk of opportunistic infections, which increases with lower CD4 counts, the following primary preventive measures should be taken for all patients with HIV, preferably in consultation with infectious disease specialists
- Initiate ART.
- Screen all patients for latent TB (see “Pulmonary complications in HIV”)
- Ensure vaccinations are up-to-date (see “Vaccinations for HIV-infected individuals” for details).
- Discontinue primary prophylaxis in individuals who respond well to ART with an increase in CD4 count; Restart primary prophylaxis if CD4 counts fall below the threshold for that specific infection.
- Primary prophylaxis is not recommended for the following due to low incidence of infection, high risk of drug-related adverse effects, and high risk of developing drug resistance:
- Bartonella spp.
- Candida spp.
- Cryptosporidium
- Cytomegalovirus
The use of live attenuated influenza vaccines is contraindicated in patients living with HIV.
Primary prevention of opportunistic infections in HIV [3] | Discontinuing prophylaxis | |||
---|---|---|---|---|
CD4 count (in cells/μL) | Opportunistic infection | Indication for primary prophylaxis | Recommended prophylaxis | |
< 250 |
|
| ||
< 200 |
|
|
|
|
< 150 |
| |||
< 100 |
|
| ||
| ||||
< 50 |
|
|
|
|
Secondary prevention [3]
- After completion of treatment for certain opportunistic infections, secondary prophylaxis of opportunistic infections (chronic maintenance therapy) should be initiated immediately and maintained until immune reconstitution occurs on ART to prevent a recurrence.
- Secondary prophylaxis should be discontinued once CD4 counts remain above the respective thresholds for > 3–6 consecutive months.
- Consult infectious disease specialists to determine when to initiate and discontinue secondary prophylaxis of opportunistic infections.
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