Q2 LONG ANSWER 10M ★ High-yield

Discuss the opportunistic infections in HIV in relation to CD4 count, including the CNS complications of AIDS.

General Medicine · Final Professional

Principle

Opportunistic infections (OIs) occur as cell-mediated immunity fails, and the CD4 count predicts which infections become possible — making it the single most useful guide to differential diagnosis in a symptomatic HIV patient. Knowing the CD4 threshold for each infection is the key examination skill.

Opportunistic Infections BY CD4 Count

CD4 count (cells/µL)	Infections and conditions
> 500	Acute retroviral syndrome, persistent generalised lymphadenopathy; same infections as the general population; tuberculosis can occur at ANY CD4 count
200–500	Pulmonary tuberculosis, bacterial pneumonia (pneumococcal), herpes zoster, oral candidiasis, oral hairy leucoplakia (EBV), Kaposi's sarcoma, seborrhoeic dermatitis, ITP
100–200	Pneumocystis jirovecii pneumonia (PCP), disseminated and extrapulmonary tuberculosis, chronic cryptosporidiosis and isosporiasis, oesophageal candidiasis, progressive multifocal leukoencephalopathy
50–100	Cerebral toxoplasmosis, cryptococcal meningitis, oesophageal candidiasis, disseminated histoplasmosis and penicilliosis, primary CNS lymphoma, HIV wasting, HIV encephalopathy
< 50	CMV retinitis and colitis, disseminated Mycobacterium avium complex (MAC), CNS lymphoma, disseminated fungal infection

CLINICAL PEARL

Learn three CD4 thresholds and you can answer most questions in this area: 200 for PCP, 100 for toxoplasmosis and cryptococcus, and 50 for CMV and MAC. And remember the exception that matters most in India — tuberculosis occurs at any CD4 count, including in patients with normal counts, so it must never be excluded on the basis of preserved immunity.

Major Opportunistic Infections

1. Tuberculosis — the commonest OI and leading cause of death in India

Presentation is atypical at low CD4 counts: less cavitation, more lower zone and miliary disease, lymphadenopathy and extrapulmonary involvement, and sputum smears more often negative. CBNAAT is the first-line test. ATT is started first, with ART added after 2–8 weeks (earlier for very low CD4, later for TB meningitis because of IRIS risk). Rifampicin interacts with protease inhibitors and dolutegravir, requiring dose adjustment or substitution with rifabutin.

2. *Pneumocystis jirovecii* pneumonia (PCP) — CD4 < 200

Subacute onset over weeks of exertional dyspnoea, dry cough and fever, with a characteristically normal chest examination despite marked hypoxia
desaturation on exertion is a valuable bedside sign. Chest X-ray shows bilateral perihilar interstitial ("bat-wing") infiltrates, or may be normal
HRCT shows ground-glass change.
Raised LDH supports the diagnosis. Confirm by induced sputum or bronchoalveolar lavage with silver or immunofluorescence staining or PCR. Treat with high-dose co-trimoxazole, adding corticosteroids when there is significant hypoxia — steroids reduce mortality in moderate to severe disease.

3. Cerebral toxoplasmosis — CD4 < 100

Reactivation of latent *Toxoplasma gondii*.
Subacute headache, fever, focal neurological deficit, seizures and altered consciousness. CT/MRI shows multiple ring-enhancing lesions with surrounding oedema, favouring the basal ganglia and grey-white junction.
Toxoplasma serology (IgG) is usually positive — a negative IgG makes the diagnosis unlikely. Treat with pyrimethamine plus sulphadiazine with folinic acid (or high-dose co-trimoxazole)
clinical and radiological improvement within 10–14 days confirms the diagnosis empirically, and failure to respond should prompt biopsy for lymphoma.

4. Cryptococcal meningitis — CD4 < 100

Insidious onset over weeks of headache, fever, malaise and vomiting, with meningism frequently ABSENT and few focal signs — the presentation is often deceptively bland.
Raised intracranial pressure is the major cause of death. Diagnose by CSF India ink stain (encapsulated yeasts), cryptococcal antigen (CrAg) in CSF and serum — highly sensitive and the test of choice, and fungal culture. CSF shows a modest lymphocytic pleocytosis with high opening pressure. Treat with induction (amphotericin B with flucytosine), consolidation (fluconazole) and maintenance, and — critically — repeated therapeutic lumbar punctures to control intracranial pressure.
ART is deferred by 4–6 weeks because of the high risk of fatal IRIS.

5. Cytomegalovirus — CD4 < 50

CMV retinitis — painless progressive visual loss with floaters; fundoscopy shows "pizza-pie" retinitis with haemorrhage and exudate along vessels. It is sight-threatening and needs urgent ophthalmological assessment. Also causes colitis (diarrhoea, bleeding), oesophagitis and encephalitis. Treat with ganciclovir, valganciclovir or foscarnet.

6. Disseminated Mycobacterium avium complex — CD4 < 50

Fever, night sweats, weight loss, diarrhoea, hepatosplenomegaly, anaemia and raised alkaline phosphatase. Diagnose by blood culture for mycobacteria. Treat with clarithromycin plus ethambutol with or without rifabutin.

7. Chronic diarrhoea — *Cryptosporidium*, *Isospora (Cystoisospora) belli*, *Cyclospora*, microsporidia, MAC, CMV — diagnosed on modified acid-fast staining of stool. Effective ART with immune reconstitution is the definitive treatment for cryptosporidiosis; co-trimoxazole treats isosporiasis.

8. Fungal and other: oesophageal candidiasis (dysphagia and odynophagia — treat with fluconazole), disseminated histoplasmosis and talaromycosis (penicilliosis), and visceral leishmaniasis (kala-azar) with HIV co-infection, which is an important and difficult problem in parts of India.

CNS Complications of AIDS

Condition	CD4	Key features	Imaging
Cerebral toxoplasmosis	< 100	Subacute focal deficit, seizures, fever	Multiple ring-enhancing lesions, basal ganglia
Primary CNS lymphoma	< 50	Slower onset, no fever, EBV DNA in CSF	Single (or few) periventricular lesion, homogeneous or ring enhancement; PET/thallium avid
Cryptococcal meningitis	< 100	Insidious headache, raised ICP, minimal meningism	Usually normal; may show hydrocephalus
Progressive multifocal leukoencephalopathy (PML)	< 200	JC virus; progressive focal deficits, visual field loss, cognitive decline; no fever	Multifocal white matter lesions, NO enhancement, NO mass effect
HIV-associated neurocognitive disorder / HIV encephalopathy	< 200	Subcortical dementia — apathy, poor concentration, slowed movement	Cerebral atrophy and diffuse white matter change
Tuberculous meningitis / tuberculoma	Any	Subacute meningitis, cranial nerve palsies	Basal meningeal enhancement, hydrocephalus, ring-enhancing tuberculoma
CMV encephalitis / polyradiculitis	< 50	Delirium, cranial neuropathy, cauda equina syndrome	Periventricular enhancement

Distinguishing toxoplasmosis from primary CNS lymphoma is a recurring clinical and examination problem: toxoplasmosis typically gives multiple lesions with positive serology and responds to a 2-week empirical trial of anti-toxoplasma therapy; lymphoma gives a solitary periventricular lesion with EBV DNA in CSF, is thallium/PET avid, and does not respond — at which point stereotactic biopsy is indicated.

Prophylaxis

Infection	Indication	Agent
PCP and toxoplasmosis	CD4 < 200 (or oral candidiasis, or WHO stage 3/4)	Co-trimoxazole — also protects against isosporiasis and some bacterial infections
Tuberculosis	All PLHIV after excluding active TB	TB preventive therapy (isoniazid-based or short-course rifapentine regimens)
Cryptococcal disease	CD4 < 100 with positive serum CrAg	Pre-emptive fluconazole
MAC	CD4 < 50 (where ART is unavailable or delayed)	Azithromycin

Prophylaxis can be stopped once ART produces sustained immune reconstitution above the relevant threshold. The single most effective prophylaxis against all opportunistic infections is effective, adherent antiretroviral therapy.

NEEDS VERIFICATION

Prophylaxis thresholds, drug regimens and the timing of ART initiation relative to each OI — confirm against current NACO and WHO guidance before printing.

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