- Infections of the brain can arise in people with HIV who have very weak immune systems
- A study found the risk of HIV-related death six times higher for HIV-positive people with a brain infection
- Researchers encouraged prompt HIV diagnosis and treatment to reduce brain infection risk
Untreated HIV infection weakens the immune system and eventually leads to a range of complications, including severe and life-threatening infections. Some of these infections can affect the brain and spinal cord. Together, the brain and spinal cord are called the central nervous system (CNS). As a result of these infections, affected people can develop seizures and strokes and face an increased risk of death.
A team of researchers in Alberta has analysed health-related information collected in databases between 1995 and 2018 (23 years). The researchers focused on data collected from 2,910 people with HIV. Over the course of the study, they found that nearly 5% of participants developed neurological infections. Most (80%) of these infections were known to herald the onset of AIDS (called AIDS-defining infections). The remaining 20% of infections were non-AIDS-defining. Over time, the risk of AIDS-defining infections declined markedly. However, the researchers found that the risk of non-AIDS-defining CNS infections remained relatively constant.
The researchers encouraged clinicians to diagnose HIV early and to initiate treatment early. Such steps would help preserve the immune system and reduce the risk of serious brain-related complications from infections.
Study details
Researchers divided neurologic infections into two categories:
AIDS-defining infections
- CMV (cytomegalovirus)
- PML (progressive multifocal leukoencephalopathy)
- cryptococcal meningitis
- coccidioidomycosis meningitis
- CNS tuberculosis
- cerebral toxoplasmosis
Non-AIDS-defining infections
- neurosyphilis
- EBV (Epstein-Barr virus) encephalitis
- HSV (herpes simplex virus) encephalitis
- varicella zoster virus (VZV) encephalitis (note that VZV can cause chickenpox in children and shingles in adults)
- S. pneumoniae
The researchers stated that “the diagnosis of neurologic infections remains challenging. Often gold standard diagnostic tests may be invasive or unsafe to perform.” As a result, doctors have to make a diagnosis by considering multiple factors—symptoms, medical history, lab test results, CT scans of the brain and even response to treatment of the neurologic infection.
According to the researchers, the study population was predominantly male (76%) and a majority were White (55%).
Results
The researchers divided the study period and found that neurologic infections were distributed as follows:
- 1995 to 2002 – 37 infections
- 2003 to 2010 – 51 infections
- 2011 to 2018 – 45 infections
Infections
The most common AIDS-defining neurologic infections were as follows:
- CMV – 36%
- toxoplasmosis – 33%
- PML – 20%
- cryptococcal meningitis – 8%
The most common non-AIDS-defining infections were as follows:
- neurosyphilis – 40%
- VZV encephalitis – 40%
Changes over time
Over the course of the study period, new cases of AIDS-defining infections fell significantly (likely due to the use of HIV treatment). However, the researchers stated that over the same period “minimal change was seen in [new diagnoses of non-AIDS-defining] neurologic infections, though the number of absolute cases was low.”
Risk factors for neurologic infections
Taking many factors into account, the researchers did not find any impact of age or sex on the risk of neurologic infections. However, they did find that people with HIV who were at increased risk of neurologic infections were more likely to:
- be African, Caribbean or Black (this point is explored later in this news bulletin)
- have had a CD4+ count that fell below 200 cells/mm3 at some point in the past
Focus on T cells
A subset of T cells called CD4+ cells helps coordinate the immune system’s response to infections. People who developed neurologic infections tended to have had very low CD4+ cell counts at some point in the past (43 cells/mm3) vs. people who did not have such infections (215 cells/mm3). Such a low CD4+ count indicates severe immune deficiency and makes people susceptible to serious infections, including those that attack the brain.
Back to neurologic infections
The researchers stated that the majority (77%) of AIDS-defining neurologic infections occurred before 2011. In contrast, the majority (80%) of non-AIDS-defining infections occurred between 2011 and 2018.
People with HIV who had a neurologic infection (regardless of its relationship to AIDS) were more likely to experience seizures and strokes (16%) than people with HIV who did not have a neurologic infection (4%).
What’s more, researchers found that people who had a neurologic infection subsequently had double the risk of death from any cause and were over six times more likely to die from an HIV-related complication compared to people who did not have a neurologic infection. This increased risk of death from HIV-related complications suggests that the presence of both HIV and certain microbes that attack the brain increases each other’s ability to cause serious injury to the immune system.
The researchers did not assess adherence to HIV treatment (ART) or the use of medicines to reduce the risk of AIDS-defining neurologic infections.
Other research has found that the risk of all AIDS-defining infections has fallen significantly in the current era. This is because of ART and its tremendous impact on strengthening the immune system.
It is very likely that the use of ART in the current era also helped to reduce the risk for AIDS-defining neurologic infections. However, there is comparatively less research on non-AIDS-defining infections in the current era.
Understanding risk factors in some African, Caribbean and Black people
As mentioned earlier, people who were African, Caribbean or Black were at increased risk for neurologic infections. The researchers proposed that factors such as “lack of culturally sensitive healthcare, higher rates of poverty, and stigma surrounding HIV diagnoses are barriers to HIV treatment, increasing the risk of developing neurologic infections.” Although these factors were not investigated further, it is possible that they were over-represented in people who were African, Caribbean or Black. The researchers also noted that people born in regions such as sub-Saharan Africa who later immigrated to Canada may be more likely to have been exposed early on in life to tuberculosis-causing bacteria and toxoplasma (the parasite that causes toxoplasmosis). Such early exposure may have increased their risk for future brain infections if they also developed severe immune deficiency related to HIV.
Non-AIDS-defining infections
In the present study, neurosyphilis was relatively common in the current era. The researchers attributed the ongoing outbreak of syphilis in Alberta to be a driving factor for neurosyphilis in their study.
There was a relatively low use of vaccines to prevent shingles and other complications (caused by VZV infection) during the study period. The cost of these vaccines was not subsidized, which may account for it not being widely used by study participants.
Advice from the researchers
A major risk factor for all neurologic infections was having a CD4+ count that fell below the 200 cell/mm3 mark at some point in a person’s life. To minimize this, the researchers called for “early HIV diagnosis and prompt initiation of ART.” To help prevent non-AIDS-defining infections, vaccines such as those that reduce the risk of shingles need to be subsidized and made available to people with HIV.
—Sean R. Hosein
REFERENCES:
- Wan MM, Gill MJ, Fonseca K, et al. Neurologic infections in people with HIV: shifting epidemiological and clinical patterns. AIDS. 2023; in press.
- Zou J, Krentz HB, Lang R, et al. Seropositivity, risks, and morbidity from varicella-zoster virus infections in an adult PWH cohort from 2000-2020. Open Forum Infectious Diseases. 2022 Aug 9;9(8): ofac395.
- Chang CC, Crane M, Zhou J, et al. HIV and co-infections. Immunological Reviews. 2013 Jul;254(1):114-42.