Advanced HIV, AIDS, and HIV-Associated Conditions

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This article will be fully reviewed, expanded, and referenced in due course
Current content focuses on core principles and exam-relevant concepts

Article Last Updated:30/03/2026

Key learning points of this article for exams:

Learn the definition of AIDS and advanced HIV disease
Recognising key AIDS-defining conditions vs non-AIDS-defining opportunistic infections
Learn further information on several important AIDS-defining conditions (detailed and labelled below)

Definition

Both AIDS and advanced HIV disease are used to refer to advanced stages of HIV infection.

Advanced HIV disease: CD4 count <200 cells/mm³ OR WHO stage 3 / 4 illness
AIDS: CD4 count <200 cells/mm³ OR presence of AIDS-defining condition

Note that WHO stage 4 illness = AIDS-defining conditions.

WHO Stage 3 Illnesses

Condition / illness	Description / notes
Unexplained severe weight loss	Persistent weight loss of >10% body weight
Unexplained persistent fever	>37.6°C Intermittent or constant >1 month
Oral hairy leukoplakia	EBV-driven White patches on the lateral tongue that cannot be scraped off
Persistant oral candidiasis	In contrast to oral hairy leukoplakia, oral candida causes white patches that CAN be scraped off
Severe bacterial infections	Pneumonia Empyema Meningitis Bacteraemia Bone / joint infections
Unexplained blood count abnormalities	Anaemia Neutropaenia Thrombocytopaenia
Unexplained chronic diarrhoea	>1 month
Pulmonary tuberculosis	TB confined to the lungs, NOT extra-pulmonary
Active necrotising ulcerative stomatitis	Gingivitis or periodontitis

WHO Stage 4 Illness (AIDS-Defining Conditions)

The following ones are more likely to be tested in exams, therefore are presented separately.

Condition	Cause	Clinical features	Investigation	Management*
Kaposi sarcoma	Soft-tissue cancer caused by HHV-8	Purple / brown painless nodules (classically on the hard palate, lower limbs, face) Can involve lungs, GI tract and lymph nodes Pulmonary Kaposi sarcoma causes haemoptysis and dyspnoea	Skin biopsy: spindle cells + vascular slits Chest X-ray / CT for lung involvement Endoscopy for GI involvement	Mainstay is ART
Pneumocystis pneumonia (PCP) – most common AIDS-defining condition	Fungs: Pneumocystis jirovecii	Progressive exertional dyspnoea Dry cough Fever Classic: desaturation on exertion Clear chest on auscultation	Hypoxia Chest X-ray: bilateral ground-glass infiltrates Bronchoscopic alveolar lavage with silver stains	Primary prevention: start co-trimoxazole when CD4 <200 Management: 1st line: co-trimoxazole Add prednisolone if hypoxic
Oesophageal candidiasis	Candida albicans	Odynophagia (classic) – may cause weight loss and anorexia Dysphagia Retrosternal chest pain Often co-exists with oral candidiasis	Upper GI endoscopy showing white plaques on oesophageal mucosa	1st line: oral fluconazole
CMV infection	CMV (HHV-5)	Retinitis (most common) Colitis (bloody diarrhoea, abdominal pain) Oesophagitis (odynophagia) Encephalitis	Fundoscopy: pizza pie appearance (from haemorrhages and exudates) Biopsy (from colon): owl-eye inclusion	Ganciclovir (IV for induction, then oral) Intravitreal ganciclovir implant for retinitis
Chronic cryptosporidiosis	Intracellular intestinal parasite: Cryptosporidium parvus	Profuse watery diarrhoea (non-bloody) Severe dehydration Abdominal pain Note cryptosporidosis is self-limiting in immunocompetent people but chronic in HIV	Stool microscopy with modified Ziehl-Neelsen stain	Mainstay is ART Supportive care (e.g. aggressive fluid resuscitation)
CNS toxoplasmosis	Intracellular parasite: Toxoplasma gondii	Subacute onset: Seizures (common) Fever Headache Focal neurological deficits Confusion, altered consciousness	MRI brain: multiple ring-enhancing lesions (typically at basal ganglia and grey-white junction) +ve Toxoplasma IgG	1st line: pyrimethamine + sulfadiazine + folinic acid Alternative: co-trimoxazole
Primary cerebral lymphoma	EBV-driven B-cell non-Hodgkin lymphoma	Subacute onset (may mimic toxoplasmosis): Headache Focal neurological deficits Seizures	MRI brain: single ring-enhancing lesion (typically periventricular) +ve CSF EBV PCR Thallium SPECT (hot in cerebral lymphoma vs cold in toxoplasmosis)	Whole brain radiotherapy Methotrexate-based chemotherapy
Progressive multifocal leukoencephalopathy	JC virus reactivation	Progressive focal neurological deficits Cognitive decline No headache and no fever (distinguishes from toxoplasmosis and lymphoma)	MRI brain: asymmetrical white matter lesions with no mass effect and no enhancement CSF JC virus PCR	Mainstay is ART No anti-JC antivirals exist
Cryptococcal meningitis	Yeast: Cryptococcus neoformans	Subacute presentation: Headache (common) Fever Altered mental status Neck stiffness is often absent Signs of raised ICP	CSF and serum cryptococcal antigen testing Lumbar puncture High opening pressure Low / normal glucose Lymphocyte predominant CSF gram staining with India Ink	Induction: IV amphotericin B + flucytosine Maintenance: fluconazole

*Assumes underlying HIV is being treated with ART – see the Human Immunodeficiency Virus (HIV) article for more information.

The remaining ones:

HIV wasting syndrome

Chronic herpes simplex

HIV encephalopathy

Disseminated mycosis

Recurrent septicaemia

Invasive cervical carcinoma

Extra-pulmonary cryptococcosis

Non-Hodgkin B cell lymphoma

Recurrent severe bacterial pneumonia

Extra-pulmonary tuberculosis

Disseminated non-tuberculous mycobacteria (e.g. Mycobacteria avium complex)

Chronic isospsoriasis

HIV-associated nephropathy / cardiomyopathy

Opportunistic Infections

Note that opportunistic infections can be AIDS-defining or non-AIDS-defining.

Key infections that are NOT AIDS-defining:

Oral candidiasis (thrush)
Pulmonary TB (see the Tuberculosis (TB) article)
Shingles (herpes zoster) (see the Shingles article)
Oral hairy leukoplakia (EBV)
Seborrhoeic dermatitis (see the Seborrhoeic Dermatitis article)

See the WHO stage 4 illness (AIDS-Defining Conditions) section above for opportunistic infections that are AIDS-defining.

HIV-Associated Complications

Key HIV-associated complications that are NOT covered in the sections above:

Constitutional symptoms	Fever Sweats Weight loss Swollen lymph nodes Fatigue
Neurological	Peripheral neuropathy HIV-associated dementia HIV-associated neurocognitive disorder
Cardiovascular	Increased risk of cardiovascular disease HIV-associated pulmonary hypertension
Metabolic	Lipodystrophy Insulin resistance Diabetes Dyslipidaemia
GI	Idiopathic HIV enteropathy Diarrhoea
Renal	HIV-associated nephropathy
Hepatic	Hep B and C co-infection Accelerated fibrosis and cirrhosis

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