HIV Headache MDM

HIV Headache MDM
Last reviewed: March 2026

Contents

MDM Templates
- Headache — No Fever, No AMS, Preserved Immunity
- Headache — Fever and/or AMS and/or Low CD4
Clinical Education
References

MDM Templates

Headache — No Fever, No AMS, Preserved Immunity

Patient with HIV (on HAART, CD4 ***, viral load ***) presents with headache. They are afebrile, non-toxic, with a reassuring neurologic exam including normal gait. No meningismus, no focal deficits, no altered mentation. No concerning skin lesions.

Given preserved immune function on HAART, the differential is similar to an immunocompetent patient. History and exam lower suspicion for CNS opportunistic infections (toxoplasmosis, cryptococcal meningitis, TB meningitis, CNS lymphoma, PML), intracranial hemorrhage, CVA, cerebral venous sinus thrombosis, and meningitis.

Plan: Treated as primary headache with reassessment after migraine cocktail and IV hydration.
Disposition: Patient back to neurologic baseline, tolerating PO, with stable reassuring exam. Discharge with return precautions for fever, worsening headache, neck stiffness, focal weakness, vision changes, or altered mental status. PCP and ID follow-up within 48 hours.

Headache — Fever and/or AMS and/or Low CD4

Patient with HIV (CD4 ***, viral load ***, HAART compliance ***) presents with headache with associated fever / altered mental status / low CD4 count placing them at risk for CNS opportunistic infections. This presentation warrants comprehensive CNS workup.

Given immunocompromised state, the differential includes toxoplasmosis, cryptococcal meningitis, TB meningitis, CNS lymphoma, PML, neurosyphilis, CMV or HSV encephalitis, viral meningitis, and intracranial hemorrhage. Presentation is not consistent with a simple primary headache.

Plan: CT head with contrast (evaluate for mass lesions) followed by lumbar puncture with extensive CSF studies (cell count with differential, protein, glucose, gram stain and culture, India ink, cryptococcal antigen, AFB, VDRL, HSV PCR). Blood cultures x2 prior to antibiotics. CXR.
Plan: Empiric coverage initiated — ceftriaxone 2g IV, vancomycin 15-20 mg/kg IV, acyclovir 10 mg/kg IV.
Disposition: Admit for continued antibiotic treatment with cultures and CSF results pending. ID consultation.

Clinical Education

CNS Differential by CD4

CD4 Count	Key CNS Considerations
>200	Primary headache, bacterial meningitis, viral meningitis, neurosyphilis, HSV encephalitis
<200	Above + toxoplasmosis, CNS lymphoma, PML (JC virus), TB meningitis
<100	Above + cryptococcal meningitis (up to 30% at this CD4), CMV encephalitis, MAC

Mass lesions on CT: Toxoplasmosis (multiple ring-enhancing lesions), CNS lymphoma (single enhancing lesion, often periventricular), TB (can present as tuberculoma). Cryptococcus typically has NO mass lesion.^[1]

Cryptococcal Meningitis

Cryptococcal meningitis has up to 30% mortality even with treatment. It is the most common opportunistic CNS infection in AIDS patients worldwide. Classic presentation: subacute headache (days to weeks), fever, and altered mental status in a patient with CD4 <100 who is not on prophylaxis.^[2]

LP findings: Hallmark is markedly elevated opening pressure (often >25 cm H2O). CSF shows elevated protein, decreased glucose, lymphocytic pleocytosis. India ink stain positive in ~70%, CSF cryptococcal antigen positive in >95%. Serum CrAg is also highly sensitive.^[2]

Treatment: Amphotericin B 0.7-1 mg/kg/day IV (induction) + flucytosine for 2 weeks, then fluconazole consolidation and maintenance. Critically, serial LPs must be performed to manage elevated ICP — drain CSF to opening pressure <20 cm H2O. Elevated ICP, not the infection itself, is what kills patients acutely.^[2]

Toxoplasmosis

Toxoplasmosis is the most common cause of focal brain lesions in AIDS. Occurs almost exclusively when CD4 <100 and the patient is not on TMP-SMX prophylaxis. Presentation: focal neurologic deficits, seizures, headache, fever, AMS.^[3]

Imaging: Multiple ring-enhancing lesions with surrounding edema on CT with contrast or MRI. Basal ganglia involvement is classic. Differentiation from CNS lymphoma can be challenging — lymphoma tends to be a single lesion and is more common when CD4 <50.^[3]

Treatment: Empiric treatment with pyrimethamine + sulfadiazine + leucovorin is initiated based on imaging in the right clinical context. Response to therapy at 2 weeks (clinical and radiographic improvement) essentially confirms the diagnosis. Brain biopsy is reserved for non-responders.

CSF Pearls in HIV

You need a LOT of CSF in HIV patients. Send at least 10-15 mL to cover the full panel: cell count with differential, protein, glucose, gram stain and culture, India ink, cryptococcal antigen, AFB stain and culture, fungal culture, VDRL, HSV PCR, CMV PCR, and cytology (for lymphoma). Don’t send a small sample and then have to repeat the LP.^[1]

ALC as CD4 proxy: If the patient’s CD4 is unknown and you’re deciding whether to LP, the absolute lymphocyte count from their CBC can guide you. ALC <1000 is predictive of CD4 2000 is predictive of CD4 >200.

References

Tan IL et al. HIV-Associated Opportunistic Infections of the CNS. Lancet Neurol. 2012;11(7):605-617. PubMed
Perfect JR et al. Clinical Practice Guidelines for the Management of Cryptococcal Disease: 2010 Update by the IDSA. Clin Infect Dis. 2010;50(3):291-322. PubMed
Vidal JE. HIV-Related Cerebral Toxoplasmosis Revisited: Current Concepts and Controversies. Front Immunol. 2019;10:1424. PubMed