Human immunodeficiency virus (HIV) is most commonly transmitted in adults via sexual intercourse and shared instruments for intravenous drug abuse.
In pediatric age, the most frequent is mother-to-child transmission (MTCT),
which can occur during pregnancy,
the process of birth and during breastfeeding.
HIV targets mainly cells bearing CD4 and chemokine receptors,
foremost activated CD4 T lymphocytes,
but also resting CD4 T lymphocytes,
monocytes,
macrophages,
and dendritic cells,
ultimately resulting in AIDS,
which opens the door for numerous opportunistic infections.
CD4-independent HIV infection of cells such as astrocytes leads to HIV encephalitis (HIVE) and HIV leukoencephalopathy (HIVL),
which manifest as HIV-associated neurocognitive disorders (HAND).
Therefore,
HIV causes CNS disease in two general ways.
Primary HIV CNS diseases are those for which the virus is both necessary and sufficient,
while secondary CNS diseases require another,
opportunistic pathogen that takes advantage of progressive immune deficiency.
HIV encephalitis
HIV infects astrocytes and microglia,
but not neurons.
Activated astrocytes,
microglia,
and perivascular macrophages produce cytokines and cause the neuroinflammation - HIV encephalitis.
The activated cells also release neurotoxic factors which cause neuronal dysfunction,
cell injury,
and death.
Advanced HIVE leads to generalized brain atrophy.
Toxoplasmosis
Toxoplasmosis is the most common coinfection in patients with HIV.
It is caused by the obligate intracellular parasite Toxoplasma gondii,
which invades CNS and forms cysts in brain parenchyma.
It is usually multifocal,
most commonly affects basal ganglia,
thalamus,
corticomedullary junction,
and cerebellum.
Most patients with toxoplasmosis present with a focal neurological deficit,
combined with symptoms of global cerebral dysfunction caused by encephalitis.
CNS cryptococcosis
The most common fungi to affect patients with HIV is Cryptococcus neoformans,
which causes CNS cryptococcosis.
It is also the third most frequent CNS pathogen in these patients,
following only the HIV and Toxoplasma gondi.
It infects CNS after reaching subarachnoid cisterns and perivascular spaces by blood.
The most common form of cryptococcosis in HIV patients is meningitis or meningoencephalitis,
but mass lesions,
cryptococcomas,
and gelatinous pseudocysts can also develop.
The most common symptoms in CNS cryptococcosis are a headache,
nausea,
and fever,
while less common focal neurological deficit.
Progressive multifocal leukoencephalopathy
Progressive multifocal leukoencephalopathy (PML) is caused by the reactivation of JC virus (JCV) in immunocompromised patients.
It is the second most common AIDS-related cause of deaths in patients with HIV,
second to lymphoma.
After reactivation and hematogenous spread,
JCV infects oligodendrocytes and causes progressive multifocal asymmetric demyelination.
Cytomegalovirus infection
Cytomegalovirus (CMV) CNS infection most commonly manifests as late-onset meningoencephalitis and ventriculitis.
It occurs in immunocompromised patients after reactivation of latent CMV and has high mortality rate despite cART.
Tuberculosis
Tuberculosis (TB) is one of the most important coinfections in patients with HIV.
It is most commonly the result of reactivation of latent disease due to the immune system insufficiency.
TB of CNS in HIV patients usually manifests as meningitis with tuberculomas and pseudoabscesses.
Neurosyphilis
Neurosyphilis is a sexually transmitted disease caused by the spirochete Treponema pallidum.
In the patients with HIV,
it has a shorter latent period for progression to clinically evident neurologic disease.
Immune Reconstitution Inflammatory Syndrome (IRIS)
Immune Reconstitution Inflammatory Syndrome (IRIS) is defined as a paradoxical clinical worsening of a known condition ("paradoxical" IRIS) or the appearance of a new condition ("unmasking" IRIS) after initiating antiretroviral therapy in patients with HIV.
It has a wide spectrum of symptoms and etiologies reported.
Most common pathogens that have been identified with IRIS are JC virus (PML-IRIS),
tuberculosis (TB-IRIS),
etc.
Primary CNS lymphoma
The introduction of HAART has reduced the incidence of AIDS-defining malignancies (ADMs).
Still,
HIV-associated primary CNS lymphoma (PCNSL),
the most common among ADMs,
remains an important medical issue.
They are the second most common focal cerebral lesion with mass effect associated with AIDS,
second only to toxoplasmosis.
Pediatric HIV infection
In the pediatric population,
the most common route of HIV infection is perinatal.
In children,
opportunistic infections and tumors are less common than in adults.
The most common CNS presentation in children is HIV encephalitis (HIVE).
Most patients are asymptomatic.