One of the greatest advantages of advanced diagnostic imaging systems is
that it enables to see the unseen. Even when a disease does not produce an
outward indication in the form of symptoms, it may remain hidden in the body,
building up strength to make a comeback when least expected. This is also
the case for the intracellular pathogen HIV
. In higher numbers, the HIV
infection exposure and in the immune system and increases
susceptibility of the host to opportunistic infections
leading to mortality. While Antiretroviral Therapy
(ART) is largely proven to be successful in
eradicating HIV from circulation and suppressing
viral load, residual virus particles may still remain
in the body. The detection of the hidden
opportunistic infection and HIV associated
malignancies in the body can be done using
A advanced imaging modalities such as PET Scan
What is the danger of HIV?
HIV infection, in addition to the apparent
symptoms, also produces less direct
effects even in patients whose infection
as been suppressed. HIV gains entry into the
body through mucosal surfaces, following
which, it rapidly disseminates throughout the
body via the lymphatic system. The virus can be
detected in lymph tissue within two days of
exposure and in the plasma within 11 days. The
immune cells positive for HIV are trapped in the
lymphoid tissue which makes the lymph nodes
themselves reservoirs of the virus and activates
inflammatory response. In this way, HIV infection
activates the immune system and triggers inflammation
Even years after ART, levels of T-cell activation markers
can remain high in the blood of HIV-infected patients. A
subtype of T cells, called as follicular T cells present in the
follicles of lymph nodes have even shown to be rich in
HIV DNA, which can be activated to produce active HIV
infection. Some of these cells may remain out of reach of
immune system because they are located in
immunologically privileged sites, where blood and
immune cells cannot reach.
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In other tissues like vascular endothelium, gut and brain, persistent infection
leads to systemic inflammation, and inflammation markers remain elevated in
the body of patients even after treatment of HIV.
HIV has also been associated with increased incidence of other conditions like
cardiovascular disease, neurological disorders, and blood and solid-tumor
Can PET scan detect HIV?
The complete eradication of HIV virus from the body is
difficult since the virus particles integrate into the host DNA prior to the initiation of ART.
These intracellular viruses often infect the CD4+ T cells which are the most common
reservoirs for latent HIV. After integrating, the infected cells have fewer than one copy
per million resting CD4+ T cell. In addition, HIV also resides in the lymphoid and other
tissues that are outside the reach of peripheral circulation. These factors make it harder
to detect by the commonly used testing techniques.
Positron Emission Tomography (PET)
which has been critical for the diagnosis, treatment, and management of
cancers and other diseases can also be used to study the direct and indirect
effects of persistent HIV infection on immune activation, inflammation, and
associated clinical comorbidities.
Resting immune cells that are activated by
HIV undergo metabolic
changes that include an increase in the rates of glucose
metabolism by around 20 times. This property can be used by F-FDG PET, which
detects the abnormal increase in FDG uptake to identify infected or malignant
tissue. Since FDG is a glucose analogue, it is broken down in a similar manner
to glucose but remains within the cells where it can be detected using PET.
While healthy or suppressed individuals have been reported to have no significant
FDG uptake, individuals with significant viral loads (early or advanced) have been
reported to have increased uptake of FDG in peripheral nodes. Some reports even
indicate that the uptake patterns of FDG were indicative of sites of viral replication.
Thus, PET involves the detection, anatomical location, and kinetics of radioactive tracer
uptake, and can provide insights into the design, implementation, and analysis of therapy
to reduce HIV reservoir burden, lower inflammation, and reduce HIV-related morbidity.
PET-CT scan can also be used to diagnose various malignancies and provide information on
potential tumor burden or sites of metastases, disease staging, and response to various
What are the Applications of FDG PET-CT in HIV?
In context of diagnosis and management of HIV, PET imaging has been useful to:
- Measure cellular metabolic activity in a variety of different clinical scenarios
- Carry out anatomical and functional neuroimaging in HIV-associated neurological diseases
- Detect central nervous system malignancies, and opportunistic infections
- Determine ART-related toxicities
- Characterize the effects of HIV on cardiovascular
Is lymphoma common in HIV patients and how to evaluate?
Lymphadenopathy (lymph node swelling) is a common symptom in HIV-infected
individuals since lymphoid tissue is a major target and reservoir of HIV. It can occur
at any HIV infection stage. Persistent lymphadenopathy often precedes the development
of lymphoma and is indicative of an increased risk of lymphoma. However, IRIS (inflammation
reaction that can occur due to HAART treatment and causes worsening of symptoms) also shows
the symptoms of lymphadenopathy similar to those seen in patients with HIV-associated lymphoma.
Thus, it is important to differentiate between benign lymphoid reaction and malignant
lymphadenopathy. PET metabolic metrics and assessment of symmetry of nodal uptake can be useful
differentiating lymphoma from reactive lymphadenopathy that arises from HAART treatment in HIV
-infected patients. However, this requires better specificity, especially in patients with abnormal
In patients with HIV infection comorbid with lymphoma, PET can assist with
identifying the extent of nodal and extra-nodal disease. PET can also distinguish between sites of
active disease and inactive residual masses while PET-CT has allowed further improvements in
diagnostic accuracy. Using F-FDG, PET can detect active lymphoid tissue during HIV-1 infection,
since distinct patterns of lymphoid activation are seen at various stages of disease activity and
even in the absence of concomitant lymphoma. This behavior is apparently related to the stage
of HIV-1 infection and increased viral loads, both of which activate CD4 + T cells and may yield
positive PET findings in lymph nodes. Thus, a distinct pattern of lymphoid tissue activation can
be seen in the head and neck region during acute disease, while there is a more generalized
pattern of peripheral lymph node activation at the mid-stages, and finally, involvement of
abdominal lymph nodes during late disease is seen.
How to Detect Arterial Inflammation in HIV?
Incidence of myocardial infarction, sudden cardiac death, and stroke is higher in HIV-infected
patients, even those who have been treated and have suppressed HIV infection. These individuals
are known to have increased arterial inflammation which creates the greater risk of cardiovascular
diseases. Arterial inflammation is partly caused due to chronic activation of macrophages.
These macrophages participate in the atherosclerotic process and reside in the bone marrow and
spleen. HIV-infected individuals also show increased inflammation of lymph nodes that harbor the
virus even after ART treatment. The inflammation of arteries and other tissues produced in HIV can
be assessed using FDG PET-CT, due to the fact that FDG accumulates in immune cells (including
those that cause inflammation reaction) because of their unusually high metabolic rates.
Identifying Disseminated AIDS-associated Burkitt's Lymphoma
Burkitt's lymphoma is a highly aggressive type of B cell lymphoma and is strongly associated with
HIV infection. In Burkitt's lymphoma, the choice of treatment and its duration depends upon the
accurate initial staging. Studies have suggested that that FDG PETCT is a sensitive modality for the
detection of viable disease in Burkitt's lymphoma.
What are the applications of PET-CT in HIV?
Application of FDG PET scan can further be useful in people living with HIV in several ways such as
- Understand the temporal changes that occur within the whole body based on the status of the
infection,ART use, or HIV reactivation
- Distinguish opportunistic infections and malignancies from direct or indirect impact of active
or suppressed HIV infection and HIV treatments
- Assist in the development of new drugs and therapies
- Aid in patient selection for various therapeutic
- Monitor responses to various therapeutic interventions
The recent years have seen a booming interest in the development of HIV-specific tracers that can
provide direct anatomical localization of HIV and identify burden of infection. One example is the
use of radiolabelled monoclonal antibodies specific to HIV envelope proteins.
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There are still some challenges to address in applying PET imaging for HIV, such as presence of
mutations that render cells resistant to the clinically available HIVspecific monoclonal antibodies,
low expression of common targets on HIV such as gp120 in patients on suppressive ART and
inability of monoclonal antibodies
to cross the blood-brain barrier.
Despite these limitations, PET imaging has the potential to enhance HIV curative and persistence
research. Novel approaches such as use of high-sensitivity
, totalbody EXPLORER imaging, PET
imaging during reactivation of latent HIV reservoir, and development of non-viral markers of
HIV persistence have the potential to overcome these limitations and can provide important
tools for the development of novel therapeutic strategies.