- Antiretroviral therapy for HIV infection successfully reduces blood
levels of the virus to almost undetectable levels.
- However persistent infection in macrophages leads to rapid
reactivation of infection should ART be interrupted.
- Future therapy needs to target HIV reservoirs such as tissue
macrophages as well to completely eliminate infection and attain a cure.
in macrophages in various parts of the body is a major
stumbling block in achieving a cure and should be addressed according to a team
of scientists at the Division of Infectious Diseases at the
University of North Carolina (UNC)
School of Medicine.
Reason for the Study
HIV infection is a major public health
concern worldwide. There is no cure or vaccine in sight though various
treatments such as antiretroviral therapy (ART)
that reduce viral multiplication and
transmission are available that
allow infected persons to lead productive lives.
However, persistence of the virus in
reservoirs such as macrophages is a major barrier to achieving eradication of the infection and to prevent its spread to other sites within the body.
‘Therapy for Human Immunodeficiency Virus (HIV) infection also needs to target macrophages along with T-cells due to new research that has identified the macrophages as major viral reservoirs.’
In an study led by J. Victor Garcia, Ph.
D., professor of medicine, microbiology and immunology at UNC School of
Medicine, he demonstrated that tissue
macrophages could support HIV replication in vivo even if there were no human
However, whether these macrophages responded to ART and whether they represented
a potential reservoir of infection even after ART treatment was not still
The current study aimed to find out the answer and to carry the
and Findings of the Study
Employing a humanized myeloid only mouse model
carrying functioning human genes
and cells but totally devoid of T-cells,
the research team were able to show the following.
- HIV infection in tissue macrophages
responded to ART.
- Following suspension of ART, there
was rapid reactivation of infection in about 1/3rd of the
animals, which corresponded to establishment of persistent infection in
"This is the first report demonstrating
that tissue macrophages can be infected and that they respond to antiretroviral
therapy," Jenna Honeycutt
the lead author
and postdoctoral research
associate in the UNC Division of Infectious Diseases said. "In
addition, we have shown that productively infected macrophages can persist
despite ART; and most importantly, that they can reinitiate and sustain
infection upon therapy interruption even in the absence of T cells - the major
target of HIV infection."
of Macrophages in HIV Infection
are cells of the white cell lineage; in blood they occur as monocytes and in
tissues they get modified to form macrophages, an important cell of the immune
system. They occur in a wide variety of tissues such as the lung, liver, brain and bone marrow.
- Macrophages in the brain and lung can survive for several weeks to years and thus macrophages
infected by HIV serve as a major reservoir of infection contributing
to reactivation of infection and inability of current therapies to
eliminate the virus completely.
- They can disseminate to
virtually all organs within the body and contribute to spread of
infection within the patient.
- Macrophages have been shown to be critical in mother to child transmission of infection via
These observations strengthen the fact
that any future therapeutic intervention to eradicate HIV
might need to target two very different types of
cells, namely the T-cells and the macrophages.
Plans For Future Research
the future, the research team hopes to elucidate the following:
Status of Current HIV Treatment and Research Trends
- Factors favoring persistent HIV infection in macrophages.
- Sites in the body where persistently infected macrophages can occur.
- Response of macrophages to possible forms of treatment aimed at
eliminating HIV infection from the body.
- Currently, the major limiting factor in HIV treatment is the inability to address viral reservoirs
and toxicities plus the cost of
treatment that could cause patients to default on treatment.
- Attempts to eradicate viral
reservoirs have been bone marrow
transplantation and gene therapy in the presence of anti-HIV therapy.
- Initiation of ART early during acute phase of the infection can restrict the
formation or the size of the viral reservoir and provide a functional
- Efforts to develop effective vaccines and alternative strategies to
achieve HIV cure are being pursued diligently.
- Cellular Reservoirs of HIV-1 and their Role in Viral Persistence - (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2683678/)
- Current Trends in HIV/AIDS - (http://jscholaronline.org/full-text/JAID/102/Current-trends-in-hiv-aids.php)