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.
- 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. 
|AIDS-defining conditions |
|CD4 count (in cells/μL)||Conditions|
|< 250|| |
|< 150|| |
- Optimize (most effective measure).
- Treat AIDS-defining condition (see relevant sections below for details).
- Prevent further opportunistic infections.
- See “ ” and “ .”
- Avoid pathogen exposure.
|Differential diagnosis of CNS lesions in HIV-positive patients with CD4 count < 200|
|Cerebral toxoplasmosis |
Primary CNS lymphoma (PCNSL) 
Cerebral abscess (bacterial) 
| || |
PML) ( 
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 
- Epidemiology: common even in patients with well-controlled HIV (affecting up to 50% of individuals) 
Clinical features 
- 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 
- More common in patients with advanced or untreated HIV 
- Due to effectiveness of HAART, elderly HIV patients more commonly develop non-HIV dementia such as Alzheimer disease than HIV-associated dementia.
- Cognitive and neuropsychological tests 
- 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
- Additional evaluation
- Cognitive and neuropsychological tests 
- Treatment: antiretroviral therapy (but avoid efavirenz) 
HAND is typically a diagnosis of exclusion.
HIV-associated distal symmetric polyneuropathy (HIV–DSPN) 
- 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
- Management of reversible risk factors (e.g., initiate ART in untreated patients with HIV, optimize management in patients with diabetes mellitus)
- Symptomatic pain management
General principles 
Patients with HIV can present with neurologic problems at any stage of infection.
- 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.
- Laboratory studies: should be guided by the pretest probability of the diagnoses under consideration
- Neuroimaging (CT or MRI brain with contrast) is indicated in all patients to assess for 
Lumbar puncture (unless there are )
- Indicated for most suspected opportunistic infections (except brain abscess)
- should include:
- See also “CSF analysis in meningitis due to atypical pathogens.” ” and “
- Brain biopsy: Consider only if needed for a definitive diagnosis after assessing the risks and benefits of the procedure.
- Treat the underlying cause.
- Seizures: Anticonvulsants should be initiated and continued for the duration of acute treatment.
Management of ↑ ICP 
- Impending herniation
- 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.
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|
|No vision loss|
|Ophthalmologic complications of HIV |
|CD4 count (in cells/μL)||Condition||Clinical features||Treatment|
|Variable||HIV retinopathy || |
|Herpes simplex keratitis |
|Varicella-zoster retinitis (acute retinal necrosis and progressive outer retinal necrosis. || |
|< 100||Toxoplasmosis retinochoroiditis |
|< 50||Cytomegalovirus retinitis || || |
- Cardiovascular abnormalities in patients with HIV include:
- The clinical presentation of and diagnostic approach to cardiovascular conditions are the same as in patients without HIV.
HIV-associated atherosclerotic cardiovascular disease (ASCVD) 
- Etiology: chronic inflammation (e.g., due to HIV infection, protease inhibitors) 
Risk assessment 
- Perform 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:
- Primary and secondary preventive measures (see “ ” 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 
- Etiology: thought to be multifactorial, including drug-induced, metabolic, or HIV-induced myocardial damage
- 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
- Epidemiology 
- Clinical features: Active TB may be subclinical or asymptomatic in patients with HIV.
- Diagnostics: similar to that of HIV-negative patients (see “Diagnostics” in “Tuberculosis”)
|Diagnosing TB in patients with HIV |
|Indications for testing||Recommended studies|
|Latent TB infection (LTBI)|
|Active TB disease|| |
- 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
- Initiate ART
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
Management: Same as for HIV-negative patients; see “Pneumocystis pneumonia.”
- Characteristic diagnostic findings
- Treatment of choice: trimethoprim/sulfamethoxazole (TMP/SMX) with or without glucocorticoids
- Special considerations in HIV
- PCP prophylaxis: See “ .”
- Common; particularly at CD4 counts < 100
- Recurrent pneumonia (≥ 2 episodes within 1 year) is an AIDS-defining illness.
- Causative pathogens
- Clinical features, diagnostics, and treatment are the same as for HIV-negative patients; see “Pneumonia” for further details.
- Prevention: inactivated are recommended; see “Immunization schedule for adults” for details. and
- In patients not already on ART, initiate treatment as soon as possible.
- Viral pneumonia (including 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) 
- Noninfectious complications 
- 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 
- 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”)
- Start ART (if not already initiated).
- Mild dysphagia/odynophagia: Diagnostic studies are not routinely required; consider a trial of empiric therapy.
- Moderate to severe dysphagia/odynophagia or failure of empiric therapy: endoscopy for examination of mucosa and biopsy
- 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).
- Diagnostics 
- Infectious diarrhea: directed antimicrobial therapy
- ART-related diarrhea: Consider an alternative ART regimen, if possible.
- Chronic diarrhea secondary to HIV enteropathy 
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. 
HIV wasting syndrome 
- CD4 count: variable (typically seen in advanced HIV)
- Clinical features: unintentional weight loss of ≥ 10% and any of the following for ≥ 30 days
Cystoisosporiasis (isosporiasis) 
- 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.
- Supportive care
- Prophylaxis: See “Primary prevention of opportunistic infections in HIV.”
- 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
AIDS cholangiopathy 
- 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
- Laboratory studies (may be normal in ∼ 25% of patients)
- Imaging: most commonly ultrasound, but MRCP or ERCP may also be used
- Liver biopsy: consider if there is diagnostic uncertainty; findings resemble those of sclerosing cholangitis.
- Malignancy: including anal cancer due to HPV, lymphoma, and Kaposi sarcoma
- Liver disease: Multiple etiologies can cause liver disease in HIV. 
- Acute pancreatitis: most commonly due to medication use, although infections and hypertriglyceridemia may also be responsible 
Renal and genitourinary complications
HIV-associated nephropathy 
- Definition: a type of advanced HIV that develops in patients with
- Risk factors: poorly controlled HIV, African descent 
- Pathophysiology: direct infection of glomerular and kidney tubular epithelial cells through HIV-1 
- Clinical manifestations 
- Diagnostics 
- Management 
- Chronic kidney disease
- Fluid and electrolyte disorders
- 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) 
- Urinary tract infections
- Epidemiology: most common hematological abnormality in patients with advanced HIV
- Etiology is multifactorial and includes;
HIV-associated thrombocytopenia 
- Epidemiology: Thrombocytopenia may be seen at any stage of the disease but is more common with increasing immunosuppression. 
- Etiology: immune-mediated destruction and ineffective thrombopoiesis
- Diagnosis: HIV-associated thrombocytopenia is a diagnosis of exclusion.
- Management 
- Malignancy is more common at low CD4 counts
- Etiology is typically multifactorial.
- Oncogenic viruses, e.g.:
- Chronic inflammation secondary to HIV infection itself
- Increased prevalence of carcinogenic risk factors, e.g., smoking
- Management 
AIDS-defining malignancies 
- Invasive cervical cancer
- Non-Hodgkin lymphoma 
Non-AIDS-defining malignancies 
- Hodgkin lymphoma 
- Lung cancer
- Hepatocellular carcinoma
- Head and neck carcinoma
- Vulvar cancer
- Penile cancer
- Anal cancer
Castleman disease 
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:
Primary effusion lymphoma (PEL) 
Differential diagnosis 
|Differential diagnosis of joint pain in HIV|
|Monoarthritis||No systemic features|
|Polyarthritis||No systemic features|
HIV-specific rheumatological conditions 
|HIV-specific rheumatological presentations |
Painful articular syndrome 
| || |
Diffuse infiltrative lymphocytosis syndrome
|Rheumatological manifestations of IRIS|| || |
|Impact of HIV and ART on rheumatological and musculoskeletal disorders|
|Systemic lupus erythematosus |
|Rheumatoid arthritis (RA) |
|Psoriatic arthritis |
|Reactive arthritis |
|Avascular necrosis || |
- 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, (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”)!
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|
|Mucosal or mucocutaneous||Plaques|
|Cutaneous||Patches or plaques|
Mucosal and mucocutaneous manifestations
|Mucosal and mucocutaneous complications in HIV infection |
|Oral hairy leukoplakia|
|Mucocutaneous candidiasis |
|Herpes simplex infections |
Human papilloma virus 
|Recurrent aphthous ulcers |
|Cutaneous complications in HIV infection|
Varicella-zoster virus 
|Molluscum contagiosum |
|Scabies || |
|Eosinophilic folliculitis |
- Bartonella infection (bacillary angiomatosis): erythematous papules and nodules
- M. tuberculosis: vesiculopapular rash that becomes necrotic in patients with miliary TB (rare) 
- MAC: papulonodular or hemorrhagic lesion on the extremities that may become necrotic
- Histoplasmosis: Papules, plaques, pustules, or ulcers 
- Cryptococcus: Erythematous papules, pustules, nodules, granulomatous, and/or verrucous lesions
- Talaromycosis 
Systemic fungal infections
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 |
|Condition||CD4 count (in cells/μL)||Clinical and diagnostic features||Management|
|Coccidioidomycosis|| || |
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 “ ” 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:
|Primary prevention of opportunistic infections in HIV ||Discontinuing prophylaxis|
|CD4 count (in cells/μL)||Opportunistic infection||Indication for primary prophylaxis||Recommended prophylaxis|