Opportunistic Infections in HIV by CD4 Count
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Direct answer
Opportunistic infections in HIV follow the CD4 count because cell-mediated immunity falls in fairly predictable steps, so the likely pathogen depends on how low the count has fallen. Pneumocystis pneumonia becomes common below 200 cells per microlitre, and cerebral toxoplasmosis and cryptococcal meningitis below 100. Cytomegalovirus retinitis and disseminated Mycobacterium avium complex cluster below 50. Prophylaxis decisions follow the count together with the clinical stage.
What you must remember
- Above 200 cells/µL: Pulmonary tuberculosis, bacterial pneumonia, oral candidiasis and herpes zoster can occur across the range and do not depend on the count alone.
- Below 200 cells/µL: Pneumocystis jirovecii pneumonia, classically with dry cough, exertional dyspnoea and bilateral ground-glass shadowing, and progressive multifocal leukoencephalopathy.
- Below 100 cells/µL: Cerebral toxoplasmosis, with ring-enhancing lesions, and cryptococcal meningitis; serum cryptococcal antigen screening is used at this level.
- Below 50 cells/µL: Cytomegalovirus retinitis and disseminated Mycobacterium avium complex disease.
- Prophylaxis: Cotrimoxazole covers Pneumocystis and toxoplasmosis; the thresholds in current national guidance should be checked against the latest NACO edition, since WHO criteria use stage and a CD4 count of 350 or fewer.
- Mycobacterium avium complex: Routine prophylaxis has become less relevant with effective antiretroviral therapy, so it is no longer the default at every low count.
- Immune reconstitution: Antiretroviral therapy can unmask latent infections, such as tuberculosis, in the weeks after starting, and this is called immune reconstitution inflammatory syndrome.
Worked scenario: headache and fever at a CD4 count of 85
A 34-year-old man with a known HIV diagnosis presents with five days of headache and fever, and a recent CD4 count of 85 cells/µL. The reasoning follows the CD4 count to a short list of pathogens, then uses the investigations to choose among them.
- Assume meningitis: Treat him as a possible cryptococcal or tuberculous meningitis until proven otherwise, sending a serum cryptococcal antigen, and plan a lumbar puncture with opening pressure after imaging if there is any focal sign.
- Image and serology: A CT or MRI showing ring-enhancing lesions raises toxoplasmosis, so Toxoplasma gondii serology is sent, while a positive cryptococcal antigen shifts the focus to meningitis.
- Start empirical treatment: Treat the most dangerous possibility promptly, and let biopsy or culture decide the final regimen.
- Time antiretroviral therapy: Start it after the infection is under treatment, often delayed by about four to six weeks in cryptococcal meningitis, because starting too early in cryptococcal or tuberculous meningitis raises the risk of harmful inflammation.
Where the examiner tests the thresholds
Four traps recur.
- Trap: assuming a low CD4 count is the only determinant. Correct: pulmonary tuberculosis can present at any count, so a patient with a count of 400 and cough is not low risk.
- Trap: confusing the prophylaxis threshold with the treatment threshold. Correct: antiretroviral therapy is started in all patients under current national approaches, while prophylaxis depends on the count and clinical stage.
- Trap: missing that cotrimoxazole covers toxoplasmosis. Correct: toxoplasma prophylaxis is indicated when IgG is positive and the count is below 100, and cotrimoxazole prophylaxis also covers it.
- Trap: placing CMV retinitis at a moderate count. Correct: it is the infection of a count below 50 cells/µL.
Frequently asked questions
Which opportunistic infection is most associated with a CD4 count below 200?
Pneumocystis jirovecii pneumonia is the opportunistic infection most associated with a CD4 count below 200. It presents with dry cough, exertional breathlessness and bilateral ground-glass shadowing on imaging. Prophylaxis with cotrimoxazole is started at this level, and serum beta-D-glucan and lactate dehydrogenase help the diagnosis.
At what CD4 count does cerebral toxoplasmosis typically occur?
Cerebral toxoplasmosis typically occurs when the CD4 count falls below 100 cells per microlitre, in people who are seropositive for Toxoplasma gondii. It causes headache, focal deficits and ring-enhancing lesions on imaging. Cotrimoxazole prophylaxis protects against it as well as against Pneumocystis.
Which test screens for cryptococcal disease in advanced HIV?
Serum cryptococcal antigen is the test used to screen for cryptococcal disease in advanced HIV, usually at low CD4 counts. A positive result prompts lumbar puncture to look for meningitis even when there are no neurological signs. Early detection and treatment reduce mortality from cryptococcal meningitis.
Which infection causes retinitis in advanced HIV, and at what CD4 count?
Cytomegalovirus causes retinitis in advanced HIV, typically when the CD4 count falls below 50 cells per microlitre. It presents with painless visual loss and haemorrhagic retinal lesions on fundoscopy. Ophthalmological review is needed for any patient with unexplained visual change at this level.
Does antiretroviral therapy prevent opportunistic infections?
Antiretroviral therapy prevents most opportunistic infections over time by restoring CD4 counts, and it is the most effective long-term protection. It does not work immediately, so prophylaxis is still needed while the count is low. Immune reconstitution can unmask infections in the weeks after starting treatment.